Vertigo refers to a false sense of motion that can occur regardless of whether a person is moving. It is not a condition in itself but a possible symptom of several medical conditions.

Physical therapy may help a person reduce or eliminate vertigo. However, they should first speak with a doctor who can determine the underlying cause.

Once the doctor has confirmed a diagnosis, they may recommend physical therapy to help improve the persons symptoms.

This article explains how physical therapy can help people who experience vertigo. It also looks at exercises that a person can try at home and explains how to find a physical therapist.

Vertigo refers to a sensation of motion that is unrelated to the persons actions, and it typically presents as a spinning sensation. It may sometimes make a person feel as though their surroundings are spinning around them.

Vertigo is a symptom of other issues. However, it can also occur alongside or lead to other symptoms, such as balance issues, nausea, and motion sickness.

There are two types of vertigo: peripheral and central.

Peripheral vertigo accounts for about 80% of cases and is often the result of benign paroxysmal positional vertigo (BPPV).

The remaining 20% of cases are central vertigo, which results from lesions on the brain stem or another issue affecting the brain.

Both multiple sclerosis (MS) and migraine can cause central vertigo.

BPPV occurs when calcium carbonate crystals in the ear, known as canaliths, come loose and move into one of the fluid filled canals.

It is the most common cause of peripheral vertigo.

These crystals interfere with the normal movement of fluid in the canals. The purpose of the fluid is to sense movement, but disturbances can cause it to send false signals to the brain.

This tricks the brain into thinking that a person is moving, even if they are not. The false signal contradicts what the other ear senses and what the eyes are seeing. This conflicting information causes a spinning sensation, known as vertigo.

Physical therapy can help with vertigo. The most suitable exercises may vary depending on the type of vertigo. A person should make sure that they have the correct diagnosis before seeking physical therapy or trying exercises at home.

Healthcare professionals may use a form of physical therapy called vestibular rehabilitation therapy (VRT) to help with vertigo. VRT may help people with vertigo resulting from BPPV, head injuries, central nervous system lesions, and undefined causes.

However, this type of therapy might not work for all causes of vertigo. The aim of VRT is to help a person anticipate vertigo from known triggers and take action to prevent it from occurring. As a result, people who experience sporadic, unpredictable incidents may not benefit from VRT.

The symptoms of vertigo may either reduce or worsen during VRT exercises.

Sometimes, worsening symptoms may be due to unnecessary overuse of the exercises on a good day, which can cause fatigue, resulting in increased symptoms.

Even if the exercises seem to have resolved the symptoms of vertigo, a person can experience a relapse of symptoms at a later time.

Some exercises for vertigo may be easy for people to do at home. However, it is important to determine the cause of vertigo before beginning any therapy to treat the symptoms.

A person should also follow all exercise recommendations from a doctor or therapist. These professionals can explain each exercise in more detail and provide guidance on what to expect and when to stop.

This section explains how to perform two canalith repositioning exercises that may help alleviate vertigo.

Learn more about exercises for vertigo.

This common exercise is particularly effective in treating BPPV.

A person can perform the Epley maneuver by following these steps:

A person should then repeat the same movement on the opposite side in other words, facing the right at the beginning. They can do this up to three times per day until they no longer experience vertigo for at least 24 hours.

Learn more about the Epley maneuver with a step-by-step video guide.

This is a similar exercise that involves alternating between sitting and lying positions.

To perform Brandt-Daroff exercises, a person should:

Learn more about Brandt-Daroff exercises with a step-by-step video guide.

A person can ask a healthcare professional for their recommendations regarding physical therapists in the area. Not all therapists will have the same level of experience, and some may not know how to treat all causes of vertigo.

A person who needs help finding a physical therapist can use the Academy of Neurologic Physical Therapys website to find a local professional in their area.

The Vestibular Disorders Association also offers a resource that can help a person find physical therapists in their area.

The costs of physical therapy can vary, but health insurance may cover some or all of the costs. A person with a health insurance plan should contact their provider to determine how much of each session it will cover.

Those without insurance should talk with a healthcare professional, who may be able to provide information on local resources that can help cover the costs.

Learn more about Medicare and Medicaid.

Vertigo treatments can vary depending on the exact underlying cause. Once a person treats the underlying cause, the symptom of vertigo should resolve.

Other treatments that can help treat some causes of vertigo include:

Learn more about home remedies for vertigo.

With physical therapy and other effective treatments, most people should see their vertigo improve. A doctor can address any underlying conditions responsible for the vertigo.

However, a person may still experience some vertigo in the future. For example, about 50% of people will experience a relapse in BPPV within 5 years. In addition, about one-third of people experiencing vertigo from anxiety will still experience symptoms after 1 year.

Vertigo is a symptom associated with several different conditions. It occurs when a person experiences spinning and dizziness or feels as though their surroundings are moving around them.

Physical therapy can help improve a persons vertigo. A person should speak with a doctor before starting any new program to make sure that they receive effective treatment for the underlying condition.

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Physical therapy for vertigo: Exercises, benefits, and more - Medical News Today

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A Texas family said they faced a fight for their childs life after their daughter's health plan provider denied coverage of a medication known as the most expensive drug in the world.

The family said doctors told them the one-time infusion that costs millions of dollars was their daughters best hope.

Read on to learn more about their story and how an "army" of strangers stepped in.

At 4-months old, every move Aniya Porter makes is a miracle to her parents.

Aniya Porter was born with a rare genetic disease called spinal muscular atrophy or SMA.

You go day-by-day. Is my daughter going to stop breathing? Is she going to stop attempting to stand up? Is she going to stop putting her head up? Will Porter said.

Aniya was born with a rare genetic disease called spinal muscular atrophy or SMA.

SMA progressively kills motor neurons, the nerve cells in the brain stem and spinal cord that control essential functions like talking, walking, swallowing and breathing.

We live every day wondering and hoping that nothing else happens to her, that she doesn't lose any more of her motor neurons, said Hailey Weihs, Aniyas mother.

There is treatment.

In 2019, the FDA approved a drug called Zolgensma which carries a price tag of $2.1 million. The one-time gene therapy, given through an IV, is designed to replace the function of a missing or non-working SMN1 gene in a patient to stop the progression of SMA preserving motor neurons before theyre gone.

It doesn't give back what she has already lost. That's why it's so time-sensitive, explained Weihs.

When Aniyas doctor prescribed Zolgensma, Weihs and Porter said their daughters insurance, a Medicaid provider in Texas, denied coverage of the drug.

She got the denial from her insurance and that was devastating for us, said Weihs.

As they appealed, they said Aniya started to show signs she may lose control of her muscles.

She started to stop having reflexes in her legs and then her tongue started twitching, said Porter.

Racing against time, Weihs connected with other families of kids with SMA and a lawyer who agreed to represent Aniya for free.

Aniyas attorney, Eamon Kelly, told NBC 5 Responds, All the doctors agree that Aniya Porter should receive this treatment.

Kelly, who is based in Chicago, said Aniya is the seventh child with SMA hes represented in insurance coverage battles.

In Aniyas case, he said the health plan provider said the treatment was not medically necessary because doctors believe Aniya has four copies of the SMN2 gene, also known as a backup gene, which can indicate a milder illness.

Kelly argued backup genes, along with other available therapies, would not be enough to keep Aniya from losing muscle function. However, he said cutting-edge gene therapy could help.

We have a treatment that will take a little girl that is going to have a degenerative disease that threatens her life, that will put her in a wheelchair and as long as we get it to her before she's two years old and before she loses her motor neurons, she'll walk, she'll dance, she'll live a full life. Its like science fiction, Kelly said.

The first child with SMA Kelly represented is Maisie Forrest, who received Zolgensma in 2019 when she was 20 months old.

Ciji Green, Maisies mom, said Maisie was on a ventilator 22 hours a day before getting the drug.

We met with her pulmonologist and I just wept, Green recalled. I told him she's not going to make it to two and he didn't offer any words of hope because he knew Maisie was on the decline as well.

Maisie is now 4 years old.

She touches my face and it's absolutely beautiful, said Green.

Maisie is playing, talking and crawling.

Something that I have now that I didn't have was hope, hope that I will get to see her continue to meet milestones that she was never supposed to meet, Green added.

Maisies mom and a team of volunteers known as Maisies Army introduced Aniyas parents to Eamon Kelly. Last month, Kelly represented Aniya at a Medicaid State Fair Hearing.

Aniyas family requested the hearing from Texas Health and Human Services.

A week after the hearing and a few days after NBC 5 reached out to Aniyas health plan provider, Superior HealthPlan, Superior told Aniyas family Zolgensma would be covered for Aniya.

We have fought for four months. Those have been the hardest four months of our lives, said Weihs.

On April 27, Aniyas family made the trip from their home in Abilene to Cook Childrens Medical Center in Fort Worth where Aniya received the drug.

She's going to sit up on her own, she is going to walk one day, she's going to feed herself with a spoon, she's going to walk down and she's going to get her diploma, Weihs said.

NBC 5 Responds reached out to Superior HealthPlan by phone and email. We didnt hear back.

We asked Texas Health and Human Services about options for families denied coverage for Zolgensma.

It told us, in part, Medicaid covers medically necessary services including medications, and those services are delivered through managed care organizations. If the prior authorization is denied, the provider or the member can appeal the decision and MCOs have flexibility to make medically necessary decisions. Members also have the right to access the State Fair Hearing process with or without an External Medical Review (EMR). The EMR is conducted by a third-party Independent Review Organization.

It also shared, Medicaid covers alternative therapies for spinal muscular atrophy treatment, including Spinraza (nusinersen) and Evrysdi (risdiplam). Also, some manufacturers offer patient assistance programs.

A spokesperson for Novartis, which makes Zolgensma, told NBC 5, in part, Zolgensma (onasemnogene abeparvovec) is a transformative and highly innovative gene therapy for a devastating, progressive genetic disease. This one-time gene therapy is priced based on the value it provides to patients, caregivers and health systems.

It also said, Novartis is working in partnership with governments and health care systems worldwide to identify and define new sustainable access models.

Aniyas parents said she will still see a doctor and be monitored after getting the gene therapy treatment. Theyre hopeful about her prognosis.

We just knew we couldnt give up, Weihs said.

Weihs tells NBC 5 Responds the family is now focused on helping other kids get access to a drug they believe is priceless.

I don't care how expensive it is. It's a child's life. Every baby deserves a chance, said Porter.

Novartis said more than 1,800 patients have been treated with Zolgensma worldwide.

Texas newborn screening program began screening for SMA last June. The states health and human services website reports SMA is among the leading genetic causes of death among infants and toddlers.

NBC 5 Responds is committed to researching your concerns and recovering your money. Our goal is to get you answers and, if possible, solutions and a resolution. Call us at 844-5RESPND (844-573-7763) orfill out our customer complaint form.

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Astrocytes make up almost half of the mammalian brain cells. They are called glial cells because scientists originally thought that these starlight-shaped structures serve as nerve glue.

Research suggests that these cells control the growth of axons, or the neuronal projections that carry electrical impulses.

However, scientists still considered astrocytes to be supporting actors behind neurons, which are the primary cells of the brain and nervous system.

Now, scientists at Tufts University in Massachusetts and other institutions realize that astrocytes may execute a significantly greater performance in brain activity.

Dr. Moritz Armbruster, a research assistant professor of neuroscience at Tufts, led a team of researchers in harnessing novel technology to study astrocyte-neuron exchanges.

To their surprise, the scientists observed electrical activity in astrocyte processes within mouse brain tissue. They reported: This represents a novel class of subcellular astrocyte membrane dynamics and a new form of astrocyteneuron interaction.

Dr. Armbruster and his fellow authors published their findings in Nature Neuroscience.

Using innovative tools, the Tufts team developed a technique to detect and observe electrical activity in brain cell interactions. These properties could not be seen before now.

Dr. Chris Dulla, corresponding author of the study, is an associate professor of neuroscience at the Tufts University School of Medicine and Graduate School of Biomedical Sciences. He explained that he and his colleagues []use viruses to express fluorescent proteins in the mouse brain, and thats what lets us measure this activity.

In an interview with Medical News Today, he elaborated:

[W]e had other experiments that made us think that this new type of activity must be happening in astrocytes. We just didnt have a way to show it[] So, we developed these new techniques to image the activity of the astrocytes and, using them, we showed that this thing that we thought must be happening actually was happening.

Neurotransmitters are chemical messengers that facilitate the transfer of electrical signals between neurons and support the blood-brain barrier. Scientists have long understood that astrocytes control these substances to support neuronal health.

This study breaks ground in showing that neurons release potassium ions, which change the astrocytes electrical activity. This modulation affects how the astrocytes control neurotransmitters.

Until now, scientists could not image potassium activity in the brain.

Neurons and astrocytes talk with each other in a way that has not been known about before, Dr. Dulla said.

Dr. Dulla maintains that human brain cells work the same way as mouse tissue. He said that mouse and human brain cells use the same proteins and molecules involved in brain activity.

Besides, using human tissue samples presents ethical challenges, Dr. Dulla noted: [We] have to be really careful and judicious [] with the experiments we design, and [we] dont get a chance to see [human tissue] samples like [we] can do with mice.

However, the professor shared that extensive databases give [scientists] a chance to just access human brain tissue without doing an experiment [themselves], but just getting the data that someone else has already done.

This wealth of information further demonstrates similarities between human and mouse cells and lets researchers deduce that the same processes are happening in each. The main difference is that human cells are larger and more abundant.

He also pointed out that the study highlights a bidirectional relationship between these brain cells, as astrocytes influence the neurons as well.

These findings about astrocyte-neuron interactions open a new world of questions regarding brain pathology, memory, and learning.

MNT also discussed this study with Dr. Santosh Kesari, who was not involved in this research. He is a neurologist at Providence Saint Johns Health Center in Santa Monica, CA, and regional medical director for the Research Clinical Institute of Providence Southern California.

Dr. Kesari said that this study confirms earlier research.

[T]his is one of many studies thats showing increasingly, how astrocytes and neurons interact, how they affect each other and then connecting the dots to how that affects brain function behavior, memory, seizures, dementia, and even in the context of brain tumors, all these cells interact. Dr. Santosh Kesari

Most medication development for brain disorders currently targets neurons. Dr. Kesari agreed that this study might shine light on a new path.

Maybe we should really be understanding the astrocyte side of things to develop drugs that may impact brain health by looking at that astrocytic role in brain disorders, he said.

The ability to image cell processes, as in this study, makes it possible to explore other activities within the brain as well.

The researchers are also screening existing drugs in hopes of manipulating astrocyte-neuron processes. Scientists could come close to repairing brain injuries or helping people increase their learning capacity if this proves successful.

They are also making their tools available to other labs to explore more areas of interest, such as breathing, headache, and many other neurological disorders.

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Researchers find new function performed by almost half of brain cells - Medical News Today

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A recent study appearing in the journaleClinical Medicinesuggests that severe COVID-19 may be associated with persistent cognitive deficits, equivalent to a decline of 10 IQ points. In this study, severe COVID-19 was defined as COVID-19 that required hospitalization and critical care.

These cognitive deficits persisted until at least 6 months after contracting the SARS-CoV-2 infection, with a gradual improvement, if any, in these cognitive symptoms. These results underscore the importance of longer-term support for patients who have recovered from severe COVID-19.

According to official data from 2020, which is the same year that this study drew its data from, about 4 in 10 adults over the age of 18 are at risk of developing severe COVID-19 in the United States.

A significant minority of individuals with a SARS-CoV-2 infection experience persistent cognitive symptoms following the initial 4 weeks after the onset of COVID-19 symptoms. Some of the common cognitive symptoms include problems with concentration, brain fog, memory, and executive function.

Although persistent cognitive symptoms are also observed in individuals with mild COVID-19, such deficits in cognitive function are more prevalent in individuals with severe COVID-19. Previous studies suggest that 36%76% of individuals with severe acute COVID-19 show cognitive deficits 6 months after illness onset.

However, further research is needed to understand the specific aspects of cognitive function that are affected after severe COVID-19 and the factors that predict these cognitive symptoms.

Previous studies characterizing persistent cognitive symptoms in COVID-19 patients have relied on self-reports, which are susceptible to bias. Other studies have used pen-and-paper neuropsychological tests to assess cognitive function.

However, these tests do not possess the sensitivity to detect small changes in cognitive function or distinguish the various domains or aspects of cognitive function impacted by a SARS-CoV-2 infection.

To address these concerns, the authors of the present study used computerized cognitive tests to objectively characterize specific domains of cognitive function impacted after severe acute COVID-19. These computerized tests also allowed the researchers to assess the magnitude of these cognitive deficits.

Individuals with COVID-19 also experience persistent mental health symptoms such as anxiety, depression, fatigue, and post-traumatic stress disorder (PTSD), which could contribute to the deficits in cognitive function.

Another objective of the present study was to determine whether these mental health symptoms mediate the persistent cognitive deficits in COVID-19 patients.

The present study involved 46 patients who were previously hospitalized for severe COVID-19 and received critical care in Addenbrookes Hospital in Cambridge, England. The former COVID-19 patients completed a series of computerized cognitive tests during a return visit to the hospital, an average of 6 months after the onset of the illness.

The performance of the 46 participants on the cognitive tests was compared with that of 460 individuals in the control group. The individuals in the control group were not hospitalized for COVID-19 and were matched for age, sex, and education levels. The researchers also used self-reports to assess symptoms of anxiety, depression, and PTSD.

The researchers found that the COVID-19 patients had a lower score and a slower response time in the cognitive tests than the matched controls. People who had COVID-19 showed more pronounced deficits in specific domains of cognition, including processing speed, attention, memory, reasoning, and planning.

Notably, the deficits in cognitive function in the COVID-19 survivors were not associated with mental health symptoms present at the time of the cognitive testing, such as depression, anxiety, and PTSD.

Instead, the performance in the cognitive tests was correlated with the severity of acute illness. For instance, cognitive deficits were more pronounced in individuals who required mechanical ventilation.

The researchers then compared the performance of COVID-19 survivors with over 66,000 individuals from the general population.

The magnitude of cognitive impairment in COVID-19 survivors was equivalent to the age-related cognitive decline expected during the 20year period between the ages of 50 and 70 years.

The studys lead author Professor David Menon, head of the Division of Anaesthesia at the University of Cambridge, says: Cognitive impairment is common to a wide range of neurological disorders, including dementia, and even routine aging, but the patterns we saw the cognitive fingerprint of COVID-19 was distinct from all of these.

Dr. Betty Raman, a cardiologist at the University of Oxford, told Medical News Today, This prospective cohort study of 46 individuals recovering from severe COVID-19 and large normative reference population by Hampshire and colleagues has shown a clear association between severity of infection and degree of cognitive impairment.

This multidimensional characterization of cognition provides a nuanced understanding of distinct patterns of cognitive impairment during the convalescent phase of severe COVID-19. Future efforts are needed to understand how this pattern varies in the context of other post-infectious syndromes and critical illness.

The study found that these cognitive deficits persisted until 6-10 months after the onset of COVID-19, and there was only a gradual improvement, if any, in cognitive performance. The persistence of these cognitive deficits highlights the importance of understanding the mechanisms underlying these symptoms.

Scientists have proposed multiple mechanisms, such as direct infection of the brain by SARS-CoV-2 and disruption of blood supply to the brain, to explain the persistent cognitive symptoms in COVID-19 patients. Among these mechanisms, systemic or whole-body inflammation has emerged as the leading candidate responsible for persistent cognitive symptoms.

Dr. Roger McIntyre, a professor of Psychiatry and Pharmacology at the University of Toronto, told MNT, Inflammatory activation appears to be mediating these findings, highlighting the hazards of lengthy immune activation. The next steps are to unravel biological mechanisms more fully and identify prevention and treatment strategies.

Discussing major questions that need to be addressed, Dr. Paul Harrison, a professor of psychiatry at the University of Oxford, said:

This study shows that these deficits can be substantial and persist more than 6 months after the acute illness. The results are convincing and important and raise further questions. For example, what happens following a less severe infection? How long do the deficits last? What causes them and, critically, how can they be treated or prevented?

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Osteoarthritis (OA) is the most common type of arthritis[1], and it is characterized by a progressive loss of articular cartilage, subchondral bone edema, sclerosis, synovitis, and marginal osteophyte formation. Pain, stiffness, and a restriction in joint movement are the most common symptoms whose severity varies. However, the condition gradually worsens over time and often results in significant functional impairment and reduced quality of life[2,3]. It was anticipated to become the fourth leading cause of disability by 2020[1,4,5], posing a significant socioeconomic burden impacting developed countries' gross domestic product[1,6]. Knee osteoarthritis (KOA) accounts for 85 percent of the global burden of OA and affects 19% of adults over 45-year-old and 37% of people over 60. KOA produces significant pain and physical impairment, lowering the quality of life and ranking as the eleventh leading cause of global disability. The average annual total expense per KOA patient is over US$15 000, resulting in total healthcare expenditure of nearly US$34 billion. Given population aging and the rise in obesity, KOA healthcare expenses are expected to quadruple by 2040[7]. It is necessary to develop sufficient medicines capable of slowing the progression of the disease and, as a result, preventing the loss of articular function and joint replacement. To provide more effective therapies, current conservative choices such as exercise and physiotherapy and weight loss with analgesics and naturally occurring substances should be integrated[1,8]. Developing effective conservative methods would be especially important for treating young people with early OA because their more active and physically demanding lifestyle negatively correlates with prosthetic implant survival[1,9].

The main treatment in the clinic is non-steroidal anti-inflammatory drugs (NSAIDs), which are recommended for all patients except those having surgical treatment in the American Academy of Orthopaedic Surgeons (AAOS) clinical practice recommendations for KOA treatment[10-12]. However, long-term usage of these treatments will cause major adverse reactions in patients, such as gastrointestinal ulcers, digestive system hemorrhage, and cardiovascular and cerebrovascular side effects, regardless of the toxicity of the drugs themselves[10,13]. Intra-articular injections of HA, platelet-rich plasma (PRP), or corticosteroids (CC) are also clinical possibilities, but their efficacy and the prevalence of side effects are still debated[10,14,15].

MSCs, be a possible treatment option for KOA[16-20]. MSCs, also called MPCs, secrete various cytokines that modulate an anti-inflammatory milieu in the OA joint, giving them immunomodulatory characteristics[18,21]. They may also have a unique ability to induce the growth of new cartilage-like cells in vitro[17,18,22], as improvements in cartilage morphology have been found in some situations[23-26]. These characteristics make them a suitable candidate for use in knee cartilage repair[27-32]. For OA treatment, orthobiologics injections containing MSCs as effector cells have recently been used. Because of their accessibility, bone marrow (BM) and adipose tissue (AD) have traditionally been the most used autologous tissue sources for orthopedic usage. In several studies, the use of autologous orthobiologics treatments in the treatment of OA is safe, with an extensive multicenter prospective analysis revealing no higher risk of neoplasia[33,34].

MSCs treatment looks to be safe based on published clinical study results. There were no significant side effects other than transitory fever in a comprehensive systematic review and meta-analysis of trials involving intravascular delivery of autologous or allogeneic expanded MSCs treatments (totaling over 1000 participants)[35,36]. A systematic evaluation of clinical trials involving intra-articular autologous expanded MSCs therapy that included 844 procedures. They had a mean follow-up of 21 months and found no link between infection, cancer, or death[35,37].

As a result, we undertook this study to examine all current high-quality information on the therapeutic efficacy and safety of MSCs in the treatment of KOA qualitatively and quantitatively. This is crucial, and the study's findings will give evidence and recommendations for the promotion and deployment of MSCs therapy in clinical practice.

We developed and implemented the study according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) system[38], the review's preferred reporting items.

Database

On December 30, 2021, we began our research using online libraries as a database. For our data gathering, we used PubMed, the Cochrane Library, and PMC.

Search Strategy

We included studies related to KOA, MSCs, and intra-articular injection. Our keywords and medical subject heading (MeSH) search strategies included knee, osteoarthritis, mesenchymal stem cells, intra-articular, and injection. The main MeSH terms used were: ("injections, intra articular"[MeSH Terms] OR ("injections"[All Fields] AND "intra articular"[All Fields]) OR "intra-articular injections"[All Fields] OR ("intra"[All Fields] AND "articular"[All Fields] AND "injection"[All Fields]) OR "intra articular injection"[All Fields]) AND ("mesenchymal stem cells"[MeSH Terms] OR ("mesenchymal"[All Fields] AND "stem"[All Fields] AND "cells"[All Fields]) OR "mesenchymal stem cells"[All Fields]) AND ("osteoarthritis, knee"[MeSH Terms] OR ("osteoarthritis"[All Fields] AND "knee"[All Fields]) OR "knee osteoarthritis"[All Fields] OR ("knee"[All Fields] AND "osteoarthritis"[All Fields])) and Knee Osteoarthritis, Mesenchymal Stem Cells, Intra-articular Injections. MeSH terms carried out a further supplementary search with free words. In addition, to prevent eliminating papers that satisfied the inclusion criteria, we searched retrieved studies that were cited.

Inclusion Criteria

We included RCTs and clinical trial studies conducted between 2017-and 2021, with complete free texts in the English language from all countries. Also, men and women aged 18 years or older with osteoarthritis in their knees and the severity of their osteoarthritis are shown in KL grade.

Exclusion Criteria

We excluded studies before the last five years, not in English, that included animals, HA, PRP, arthroscopy, ultrasound waves, and combination treatment in the intervention, other than knee joints like shoulder and hip.

Quality Assessment Tools

Two authors, S.S and S.V, independently assessed the study's overall quality and risk of bias by using the Cochrane Collaboration risk-of-bias tool for the RCTs and Newcastle Ottawa Scale (NOS) for the clinical trials. The Cochrane Collaboration risk-of-bias tool included random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. Each included RCT was rated as having a low, unclear, or high risk of bias based on these factors. The following are the contents for the NOS, including selection, comparability, and outcome. According to these items, each included clinical trial was scored as good, fair, and poor quality.

Data Extraction

Two writers, S.S and S.V, worked independently to extract data using a standardized manner. Disagreements that arose during the procedure were resolved through debate between the two writers or contact with a third author, just as they were with the inclusion of literature into the study. The following were the contents of the data extraction form: the first author's name, the year of publication, the sample size, basic patient information (age, male-to-female ratio, body mass index (BMI)), osteoarthritis grading KL grade, donor source (autogenous/allogeneic), cell processing, culture, and harvesting, number of cells, immunophenotype, intervention, and control situation, follow-up, and outcome clinical effectiveness and safety were among the outcomes.

Literature Search

Using the literature search, we discovered 78 relevant papers. After eliminating duplicates and screening titles and abstracts, 50 articles were excluded. The remaining 18 articles were subjected to a full-text review, with eight being excluded, as shown in figure1.

Characteristics of the Included Studies

A total of six RCTs (577 participants)[2,7,17,18,32,35], including one study which had a pilot study, commenced in November and completed in June 2021, where recruitment commenced in January and August 2021 and will be finished by December 2024[7]. Four clinical trial studies, including three prospective[16,23,32], and one retrospective[33]clinical trial, were included in this systematic review. Publication intervals for all 10 were from 2017 to 2021[7]. All studies used autologous MSCs except two studies[2,7], which used allogeneic MSCs. Five studies[2,17,18,35,39], used AD-MSCs two studies[23,32], used BM-MSCs, one study[16], used BMA, one study[33], used both concentrations BMAC and MFATand one study[7], used multipotent MSCs. A placebo was utilized as a control group[2,39]. For one study, NS was used as the control group[7]; for one trial, HA was used as the control group[17], In one study's control group, cautious management was adopted[35], and five of the investigations[16,18,23,32,33], were uncontrolled. Furthermore, four trials[2,16,17,35]were monitored for a year, three trials[7,23,32]were monitored for 24 months, and two trials[33,39]were followed for six months after they were completed, and one study[18], had a 48-weeks follow-up period. Table1illustrates the features of the 10 articles that were featured.

Risk of Bias Assessment

Figure2shows the results of the risk of bias evaluation for six studies[2,7,17,18,35,39], while table2shows the results of the NOS for four studies[16,23,32,33]. Lee et al.[39], although relevant images were drawn, we could not retrieve the original data and conduct the combined statistics; hence this study was classified as having a high risk of reporting bias. Freitag et al. and Kuah et al. incomplete data on overall WOMAC scores and subscales (pain, stiffness, and function) were also given, and one or more of these characteristics may have been missing. As a result, attrition bias was found to be considered a risk in these two investigations[2,35]. Freitag et al. performed BM or subcutaneous tissue extraction only in the intervention group. Even though moral restraint precluded the same measures from being used in the control group, this study was classified as having a high risk of detection and performance bias[35].

Outcomes

Knee Injury and Osteoarthritis Outcome Score (KOOS): A total of seven studies[7,16,23,32,33,35,39]reported KOOS[40]at baseline and final follow-up in the intervention and the control groups, including 650 patients. Three studies[7,23,32] were followed up for 24 months, two studies[16,35]were followed up for 12 months, and two studies[33,39]were followed up for six months. Normalized KOOS was used to measure positive changes in all five primary areas, and all were significantly better at six, 12, and 24-months post first injection[32]. Significant improvements in Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) scores were observed over time (F (4,12) =12.29, p<0.001) in a cohort. Following the procedure, clinical significance was accomplished at three, six, and 12-months following the procedure[16]. As evaluated by normalized KOOS, table3demonstrates the favorable changes in all five essential categories. All were much improved at six, 12, and 24 months after the first treatment[32]. Using all sample time points, the Sport Score and quality of life (QOL) score were nominally linked with an unadjusted p-value of 0.031 and 0.046, respectively[23].

Magnetic Resonance Imaging (MRI) Evaluation

A total of eight studies reported MRI evaluation at baseline and follow-up in the groups, including 659 patients[2,7,17,18,23,32,33,39]. Three studies[7,23,32]were followed for a total of 24 months, for 12 months, two studies[2,17]were followed up on, and two studies[33,39]were followed up for six months after they were completed, and one study[18], had a 48-weeks follow-up period. The transformation of the central medial femorotibial compartment (cMFTC) cartilage thickness[41]for a 24-month was 0.32 mm (SD=0.40) for those who have narrowed medial tibiofemoral joint and maintained knee pain at baseline in comparison to the control neither of which radiographic nor pain development (0.12mm, SD=0.28)[7,42]. 67 percent of patients had progressed cartilage degeneration within the control group, with another 56 percent having extended osteophyte formation. Only 30% of individuals saw additional cartilage loss in the one-injection group, whereas 50% experienced osteophyte development advancement at 12 months. In the two-injection group, 89 percent of participants had cartilage improvement or no progression in cartilage loss, indicating that OA had stabilized, as seen by 89 percent of subjects having no progression in osteophyte formation[35]. The size of the cartilage defect in the MSCs group did not change substantially on MRI at six months (p =.5803), but the size of the cartilage defect in the control group grew significantly (p =.0049). Furthermore, the change in cartilage defect following the injection was significantly different between the two groups (p =.0051)[39]. Using the WORMS technique, the low-dose group had a mean change from baseline of -0.36 and -0.86 in both the left and right knees at week 48. Furthermore, the mean changes in total cartilage volume, knee femur end cartilage volume and knee patellar cartilage volume in the low-dose group were 54.58, 38.63, and 39.69 mm, respectively. The knee tibial end cartilage volume and knee cartilage volume in the medium-dose group improved by 243.32 and 34.44 mm, respectively. Increases of -0.42 and 122.92 mm in the left knee WORMS and knee femur end cartilage volume were reported in the high-dose group[18].

Two bilateral intra-articular knee injections, three weeks apart (18-20 days), were used in this preclinical study with AlloJoin. Because the high prevalence of bilateral KOA in the treatment population was investigated[18,43,44]. MRI showed no significant change in cartilage thickness after six months. As indicated in Table4, there was a considerable improvement in knee cartilage thickness in the femoral and tibia plates after 12 months[32]. Time 2 (T2) scores in the patella region increased by a negligible amount (p =.055 for a two-sided test, nonadjusted). T2 changes (from baseline to 12 months) did not differ across the one, 10, or 50 million BM-MSCs cohorts[23]. The 50 million BM-MSCs doses (effect estimate [B] = 1.828, p =.002) maintained synovitis at lower levels than the one million BM-MSCs dose, according to statistical analysis of the effects of dose adjusted for both time and baseline levels of synovitis[23]. We found a decrease in pro-inflammatory monocytes/macrophages in synovial fluid three months after MSCs infusion, suggesting a potential mechanism of action. We do not see statistical significance relative to baseline levels (p =.062) because of the small number of patients who presented synovial fluid at baseline and three months after MSC infusion (n = 5). However, this downregulation suggests a potential mechanism of action of MSCs in the arthritic joint[23].

Visual Analogue Scale (VAS)

A total of five studies[2,17,18,33,39]reported VAS evaluation at baseline and follow-up in the groups, including 194 patients. Two studies[2,17]were followed up for 12 months, two studies[33,39]were followed up for six months, and one study[18]was followed up for 48 weeks. VAS32[7], (P < .00001)[10], (p 0.005) in Progenza (PRG) combined group[2]. In the MSCs group exclusively, the VAS for knee discomfort dropped dramatically from 6.8 0.6 to 3.4 1.5 (p.001)[39]. Our VAS data confirmed clinical improvement with these cell injections, as seen by the study's reported VAS minimal clinical improvement differences (MCID) score of 30.0 mm[18,45,46].

Western Ontario, and McMaster Universities Osteoarthritis Index (WOMAC)

A total of six studies[2,17,18,23,35,39]reported WOMAC[47], evaluation at baseline, and follow-up in the groups, including 160 patients. Three studies[2,17,35]were tracked for 12 a year, one trial[23]was monitored for 24 months, one study[18]had a 48-weeks follow-up period, and for six months, one trial[39]was followed. (All P values were less than .05)[10]. Also, compared to the HA group, significantly more individuals had a 50% improvement in WOMAC, and after 12 months, the Re-Join group had a 70% improvement rate, indicating that more patients were improving[17].

At six months after injection, a single injection of AD-MSCs resulted in a 55 percent reduction in the WOMAC total score, a 59 percent reduction in the WOMAC pain score, a 54 percent reduction in the WOMAC stiffness score, and a 54 percent reduction in the WOMAC physical function score[39]. According to a study in previous research[24,48-50], clinical outcomes improved six months following MSCs injection. The findings of this investigation support this. Furthermore, similar to earlier research[49,50], even six months following injection, the clinical outcomes were still good. This finding implies that with a single intra-articular MSCs injection, symptom alleviation can be sustained for up to six months[39]. Improvements in short form 36 (SF-36), -23.71 in WOMAC total, -17.14 in WOMAC-function, -2.29 in WOMAC stiffness, and -4.29 in WOMAC-pain were seen in the low-dose cohort. Improvements in left knee VAS were -2.25, right knee VAS was -2.13, WOMAC-total was -16.50, WOMAC-function was -11.88, WOMAC-stiffness was -1.71, and WOMAC-pain was -3.25 in the medium-dose cohort. The high-dose cohort observed statistically significant improvements in the left knee VAS of -1.36 and the right knee VAS of -2.07[18]. The MCID averages for the WOMAC with KOA have been published[51]. The WOMAC functional score ranges between 9.1 to 19.9 mm, indicating that the WOMAC scores in this trial indicated considerable clinical improvement for the overall WOMAC functional (17.1) for both the left and right knees after 48 weeks for two of the doses[18,52-55].

Adverse Events (AEs)

A total of four studies[7,16,17,32]reported AEs evaluation at baseline and follow-up in the groups, including 550 patients. Two studies[7,32]were followed up for 24 months, and the others[16,17]were followed up for 12 months. Patient satisfaction was high (range: 8.12.1-8.81.9). All the patients said they would recommend the treatment to a friend, and 85 percent said they would do it again[16]. In the MSCs group, 10 (83%) patients experienced AEs, compared to seven (58%) individuals in the control group. No significant AEs or grade 4 or 5 AEs on the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale. All the grade 3 AEs on the NCI-CTCAE scale were arthralgia, which completely disappeared within three days[39,56]. In the low-, middle-and high-dose groups, the incidence of AEs was 71.42 percent (5/7), 87.50 percent (7/8), and 100 percent (7/7), correspondingly[18].

We evaluated the clinical efficacy and safety of intra-articular injection of MSCs in this study by thoroughly analyzing six RCTs and four clinical trials. The study's first strength is its comprehensiveness, a compilation of all current high-quality studies. Second, we assessed the included studies' cell adherence, cell immunophenotype, and cell differentiation ability using the MSC criteria established by the Mesenchymal Stem Cell Committee of the International Society for Cell Therapy (ISCT), and discovered that half of them meet the minimum requirements[16,18,23,35,39], as shown in table1. Third, it contains tight inclusion and exclusion rules. Concurrent therapy studies, such as HA and PRP were omitted. The addition of newly incorporated research of AT and BM sources, we believe, is what has led to the divergent results. This is one of the reasons we are so adamant about completing this research. Compared to the control group, the MSCs group showed a considerable increase in cartilage volume.

The selection of the appropriate donor source and the optimal dose has become an essential issue due to the extensive research into MSCstherapy. BM, AT, placenta, and umbilical cord are among the most popular donor sources for MSCs in clinical research. Initially, people preferred to cultivate and expand BM-MSCs. Later research discovered that AT was more accessible than BM, had a simpler isolation technique, a larger yield, and the same chondrogenic capacity[10,57,58].

A reduction in pain is connected to the ability of cells to release bioactive chemicals. These elements are hypothesized to change the inflammatory milieu in the joint from pro-inflammatory to anti-inflammatory. PRG includes a high concentration of these bioactive substances in the cell culture supernatant, unlike other cell therapies. PRG may decrease the progression of OA based on the favorable cartilage outcomes from preclinical and clinical investigations. Many studies have found that beneficial effects are primarily apparent in the lateral tibial region. Although OA affects the entire joint, it has been hypothesized that the medial tibiofemoral region is more severely damaged than the lateral tibiofemoral region. As a result, because the medial tibiofemoral region is later, there may be fewer opportunities to demonstrate progress[2].

MPCs tagged with fluorescent dye lasted locally in the joint for up to 10 weeks in preclinical rat studies before becoming undetectable[18,59]. Furthermore, the serious adverse events (SAEs) contradict all preclinical animal investigations that revealed no evidence of systemic exposure[18,59-61]. In addition, earlier research has shown that Re-Join is beneficial in rabbit and sheep models of OA[17,60,61]. The repair of osteoarthritis in rabbits and goats appears to be mediated by paracrine effects involving the stimulation of endogenous repair systems[26,32]. In a systematic evaluation of MSCs therapies, Lalu et al. found no significant side effects[23,62,63]. Following the aspiration of BM, there were no systemic side effects observed, and there were no issues that were noted[23]. Therefore, no individuals dropped out of the study[2].

Our findings show that there are statistically significant improvements in pain and function[2,7,10,16-18,33,35]. The average percentage of patients who have passed the Patient-Acceptable Symptom State (PASS)[64]the threshold was 35% in the placebo cohort(ranging from 33.1 to 35.5) and 48% in the intervention cohorts (varying between 42.2% to 56.1%)[7,65,66]. There were also decreases in present, typical, best, and worst numerical rating scale (NRS) pain[67], scores statistically significant over time (F(4,12)=14.5, p<0.001; F(4,12)=17.5, p<0.001; F(4,12)=2.9, p=0.003; and F(4,12)=35.5, p<0.001, respectively)[16]. Also, NRS pain in both the single and two injection protocol treatment groups, when compared to baseline, within-group improvement was statistically significant (0.05) at all time intervals[35]. Therefore, we found that all statistical tests for pain and functional outcome measures (n = 21) had a mean power of 0.877 15 SD[35]. The NPRS improved by 69 percent from baseline to the last follow-up at 12 months in both therapy groups. In comparison, arthroscopic debridement resulted in a 14 percent improvement in pain scores after 12 months, while a prescribed exercise regimen resulted in a 12 percent improvement in pain scores[35,68,69]. The range of motion in the MSCs group improved considerably from 127.9 10.3 to 134.6 12.5 at six months after injection (p =.0299)[39]. When these established MCID values were applied at 48 weeks, there was a reduction in pain and an improvement in knee function; however, due to the small number of participants included in this pilot investigation, these findings should be regarded with caution[18].

In addition, they discovered a link between the number of cells injected and pain relief[33]. Furthermore, two RCTs were recently reported, revealing significant improvements in pain and function in KOA patients after injection of autologous AD-MSCs versus controls[33]. MSCs generated from autologous BM showed a significant increase in clinical ratings[33,39]. Because the researchers differ in study design, cell type, supplementary therapy, and rehabilitation methods, it is difficult to determine the true differences in intra-articular injections of BM-MSCs and AD-MSCs[39].

Data reveal that one or more outcomes, such as KOOS pain, have improved statistically significantly[23,32,35], symptoms, SF-36[18], VAS[2,10,16,18,33,39], and QOL scores[17,23,33], as well as WOMAC stiffness[2,10,16-18,23,33,35,39]. NPRS improved[16,35], from baseline to final follow-up at 12 months, by a percentage of 69 percent previous clinical trials have shown that intra-articular MSCs treatment can slow the course of OA[35]. All symptoms decreased dramatically, resulting in a considerable improvement in the quality of life of these grade 2 to 4 KOA patients. There is also evidence of safety. However, more research is required. Another concern is that most research focuses on short-term safety rather than long-term results[32]. Starting three months after the procedure, KOOS-JR scores improved dramatically, with clinically meaningful improvements lasting 12 months[16]. Within 48 weeks of follow-up, MCID scores for SF-36 are approximately 10%, which this study's data has surpassed[18,53,70,71]. Both groups improved significantly in Emory Quality of Life (EQOL), VAS, and all KOOS indicators pre-and post-procedure (p < .001)[33]. During follow-up, the two treatment groups' EQOL ratings altered in similar ways (similar temporal patterns across time) (p =0.98, test for interaction between time on study and treatment group)[33].

We report putative chondroprotective benefits and decreased synovial inflammation, with the 50 million cell dosage potentially being more beneficial. However, when compared to the 50 million and/or 10 million BM-MSC dosages, serum carboxy-terminus of the three-quarter peptide from cleavage of C I and C II (C1, C2), urine type II collagen cleavage neoepitope (C2C), and C-telopeptide of type II collagen (CTX-II) all increased significantly, suggesting a chondroprotective MSCs dose effect, as previously described[23]. Furthermore, exploratory MRI analyses of average cartilage volumes and average WORMS from baseline at week 48 revealed no change in the medium-dose (2*107 cells) and high-dose (5*107 cells) groups but an improvement in the low-dose AlloJoin (1*107 cells) group[18]. Over radiography x-rays, MRI assessments offered a more accurate picture of articular cartilage deterioration and change in location of the menisci[18,72]. Because MOAKS[73]is a semi-quantitative metric, the MRI analysis is limited[18]. Furthermore, MOAKs analysis demonstrating effective stabilization despite continuous bone marrow lesions (BMLs)contrasts with previous research that has found a link between BMLs and OA progression[35].

Because Orozco et al. showed a consistent improvement in cartilage quality during a two-year follow-up period from the baseline, we expect cartilage improvement in our series over a longer follow-up time[39,48]. Our research also saw increased cartilage volume and quality[2,17,18,23,32,39]. Furthermore, an MRI examination at 48 weeks revealed no signs of ectopic bone development[18]. Intra-articular injections of Re-Join were found to enhance cartilage volume, with a significant rise 12 months after injection, suggesting that this could be a viable therapeutic intervention and cartilage regeneration for OA patients[17].

We believe that the subsequent trials should be greater[23]. The following trials should, in our opinion, be larger[18]and also look at the MSCs dose and the MSCs source. The safety of allogeneic MSCs for KOA must be established[23,32,39]. The usage of allogenic MSCs can be standardized, the dose can be more precisely regulated, and cell variability may be minimized. We should also examine the efficacy of BM and AD-derived orthobiologics treatments to develop a reliable judgment on which is the better choice for treating KOA[33]. MSCs, we feel, has the potential to be a definitive treatment for KOA[32]. It is also critical to distinguish the findings of this study from those of previous studies that used more various cell-based products, such as stromal vascular fraction[35].

This research has several limitations. The results should be treated with care first and foremost. We did our utmost to avoid simultaneous surgical treatment affecting efficacy. Second, all the studies we looked at used intra-articular injections. MSCs implantation by open or arthroscopic surgery has been proven to be more conducive to cartilage repair in several studies. While MSCs transplantation on a scaffold may help rebuild the anterior cruciate ligament and meniscus[10]. Third, four of our studies[16,23,32,33], were not RCTs. Fourth, we included three studies[23,33,39]that included KL grade 4 KOA patients. We do not know if the disease can be slowed or even reversed at this point in the disease's progression, especially using autologous-derived MSCs. Furthermore, as the human body ages, MSCs' ability to self-renew and differentiate decreases; particularly, the potential of MSCs in individuals with OA is lower than that of healthy persons[10,17,23,33,35].

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Safety and Efficacy of Injecting Mesenchymal Stem Cells Into a Human Knee Joint To Treat Osteoarthritis: A Systematic Review - Cureus

Bone Marrow Stem Cells Comments Off on Safety and Efficacy of Injecting Mesenchymal Stem Cells Into a Human Knee Joint To Treat Osteoarthritis: A Systematic Review – Cureus | May 13th, 2022

You should read the following discussion and analysis of our financial conditionand results of operations together with the condensed consolidated financialstatements and related notes included in Part I, Item 1 of this Quarterly Reporton Form 10-Q (this "Quarterly Report") and with the audited financial statementsand the related notes included in our Annual Report on Form 10-K for the fiscalyear ended December 31, 2021 filed with the Securities and Exchange Commissionon March 18, 2022. Certain of the information contained in this discussion andanalysis or set forth elsewhere in this Quarterly Report, including informationwith respect to plans and strategy for our business, includesforward-looking statements that involve risks and uncertainties. As a result ofmany factors, including those factors set forth in the section entitled "RiskFactors", in Part II, Item 1A of this Quarterly Report, our actual results coulddiffer materially from the results described in or implied by theforward-looking statements contained in the following discussion and analysis.You should carefully read the section entitled "Risk Factors" to gain anunderstanding of the important factors that could cause actual results to differmaterially from our forward-looking statements. Please also see the section ofthis Quarterly Report entitled "Cautionary Note RegardingForward-Looking Statements." The events and circumstances reflected in ourforward-looking statements may not be achieved or may not occur, and actualresults could differ materially from those described in or implied by theforward-looking statements contained in the following discussion and analysis.As a result of these risks, you should not place undue reliance on theseforward-looking statements. We assume no obligation to revise or update anyforward-looking statements for any reason, except as required by law.OverviewWe are a clinical-stage biotechnology company dedicated to enabling curesthrough hematopoietic stem cell therapy. We are focused on the development andcommercialization of safer and more effective conditioning agents and mRNA-basedstem cell engineering to allow for expanded use of stem cell transplantation andex vivo gene therapy, a technique in which genetic manipulation of cells isperformed outside of the body prior to transplantation. We are also developingnovel therapeutics directed at diseased hematopoietic stem cells.Our drug development pipeline includes multiple product candidates designed toimprove hematopoietic stem cell therapy. Our lead product candidate, JSP191, isin clinical development as a novel conditioning antibody that clearshematopoietic stem cells from bone marrow in patients prior to undergoingallogeneic stem cell therapy or stem cell gene therapy. We plan to initiate aregistrational clinical study in acute myeloid leukemia ("AML") patientsundergoing stem cell transplantation by the end of the first quarter of 2023.Based on the single agent depletion observed in our Phase 1 study ofmyelodysplastic syndrome ("MDS") patients undergoing stem cell transplant, weare also initiating a pilot study of JSP191 as a therapeutic in lower-risk MDS,which we expect to commence in the second half of this year. Beyond JSP191, weare developing stem cell grafts transiently reprogrammed using mRNA that have acompetitive advantage over endogenous hematopoietic stem cells ("HSCs"),enabling higher levels of engraftment designed to remove the need for highlytoxic conditioning of the patient and lower the risk of other seriouscomplications that limit current stem cell transplants. We plan to continue toexpand our pipeline to include other novel stem cell therapies based on immunemodulation, graft engineering and cell or gene therapies. Our goal is to expandthe use of curative stem cell transplant and gene therapies for all patients,including children and the elderly.Stem cell transplantation is among the most widely practiced forms of cellulartherapy and has the potential to cure a wide variety of diseases, includingcancers, genetic disorders, and autoimmune diseases. Yet currently, patientsmust receive highly toxic and potentially life-threatening conditioning agentsto prepare their bone marrow for transplantation with either donor stem cells ortheir own gene-edited stem cells. Younger, fitter patients capable of survivingthese toxic side effects are typically given myeloablative, or high-intensity,conditioning whereas older or less fit patients are typically given reducedintensity, but still toxic, conditioning which leads to less effectivetransplants. These toxicities include a range of acute and chronic effects tothe gastrointestinal tract, kidneys, liver, lung, endocrine, and neurologictissues. Depending upon the conditioning regimen, fitness of the patient, andcompatibility between the donor and recipient, the risk of transplant-relatedmortality ranges from 10% to more than 50% in older patients. Less toxic ways tocondition patients have been developed to enable transplant for older patientsor those with major comorbidities, but these regimens risk less potent diseaseelimination and higher rates of disease relapse. Even though stem cell therapycan be one of the most powerful forms of disease cure, these limitations ofnon-targeted conditioning regimens have seen little innovation over the pastdecade. 20Our lead product candidate, JSP191, is a monoclonal antibody designed to blockthe specific signal on stem cells required for survival. It is currently indevelopment as a highly targeted conditioning agent prior to stem cell therapyas well as a therapeutics in lower-risk MDS patients, which we expect tocommence in the second half of 2022. We are also sponsoring two clinical studiesof JSP191 as a conditioning agent prior to stem cell transplant. The firstclinical study is an open label Phase 1/2 trial in two cohorts of severecombined immunodeficiency ("SCID") patients: patients with a history of a priorallogeneic transplant for SCID but with poor graft outcomes and newly diagnosedSCID patients. The primary endpoint in this study is to evaluate the safety andtolerability of JSP191. The secondary goal of this study is to evaluate theefficacy of JSP191 as a conditioning agent in conjunction with a stem celltransplant. Based on preliminary results from our ongoing Phase 1/2 clinicaltrial, we believe JSP191 has demonstrated the ability as a single agent toenable engraftment of donor HSCs as determined by donor chimerism, or thepercentage of bone marrow cells in the patient that are of donor origin aftertransplant. Engraftment was observed in seven out of ten T-B-NK+ SCID patientswith prior allogeneic transplant, as evidenced by CD15+ donor chimerism of morethan 5% averaged from 12-24 weeks post-transplant. Increased nave donor T cellproduction was observed in the majority of T-B-NK+ subjects, as well as clinicalimprovement. No JSP191 treatment-related serious adverse events ("SAEs") havebeen reported to date and pharmacokinetics have been consistent with earlierstudies in healthy volunteers. We expect to complete enrollment in this Phase1/2 clinical trial by mid-2023.

The FDA has granted rare pediatric disease designation to JSP191 as aconditioning treatment for patients with SCID. In addition, the FDA grantedorphan drug designation to JSP191 for conditioning treatment prior tohematopoietic stem cell transplantation.

We expect our expenses will increase substantially in connection with ourongoing and planned activities, as we:

? advance product candidates through preclinical studies and clinical trials;

? procure the manufacture of supplies for our preclinical studies and clinical

? attract, hire and retain additional personnel;

? operate as a public company;

? implement operational, financial and management systems;

? pursue regulatory approval for any product candidates that successfully

? establish a sales, marketing, and distribution infrastructure to commercialize

any product candidate for which we may obtain marketing approval and related

commercial manufacturing build-out; and

? obtain, maintain, expand, and protect our portfolio of intellectual property

Business Impact of the COVID-19 Pandemic

Stanford License Agreement

Other collaboration and clinical trial agreements

Collaboration with Stanford University

Components of Results of Operations

External research and development costs include:

? costs incurred under agreements with third-party CROs, CMOs and other third

parties that conduct preclinical and clinical activities on our behalf and

manufacture our product candidates;

? costs associated with acquiring technology and intellectual property licenses

that have no alternative future uses;

? consulting fees associated with our research and development activities; and

? other costs associated with our research and development programs, including

Internal research and development costs include:

? employee-related costs, including salaries, benefits and

stock-based compensation expense for our research and development personnel;

? other expenses and allocated overheads incurred in connection with our research

Our future research and development costs may vary significantly based onfactors, such as:

? the scope, rate of progress, expense and results of our discovery and

preclinical development activities;

? the costs and timing of our chemistry, manufacturing and controls activities,

including fulfilling cGMP-related standards and compliance, and identifying and

? per patient clinical trial costs;

? the number of trials required for approval;

? the number of sites included in our clinical trials;

? the countries in which the trials are conducted;

? delays in adding a sufficient number of trial sites and recruiting suitable

patients to participate in our clinical trials;

? the number of patients that participate in the trials;

? the number of doses that patients receive;

? patient drop-out or discontinuation rates;

? the duration of patient participation in the trials and follow up;

? the cost and timing of manufacturing our product candidates;

? the phase of development of our product candidates;

? the efficacy and safety profile of our product candidates;

? the timing, receipt, and terms of any approvals from applicable regulatory

authorities, including the FDA and non-U.S. regulators;

? maintaining a continued acceptable safety profile of our product candidates

following approval, if any, of our product candidates;

? changes in the standard of care on which a clinical development plan was based,

which may require new or additional trials;

? the extent to which we establish additional strategic collaborations or other

? the impact of any business interruptions to our operations or to those of the

Other Income (Expense), Net

Three Months Ended March 31, 2022 and 2021

The following table summarizes our results of operations for the three monthsended March 31, 2022 and 2021 (in thousands):

Research and Development Expenses

The following table summarizes our research and development expenses for thethree months ended March 31, 2022 and 2021 (in thousands):

Our external costs by program for the three months ended March 31, 2022 and 2021were as follows (in thousands):

General and Administrative Expenses

Liquidity and Capital Resources

Future Funding Requirements - Going Concern

Contractual Obligations and Commitments

We have contractual obligations and commitments as described in Note 9,Commitments and Contingencies, within our condensed consolidated financialstatements included in Part I, Item 1 of this Quarterly Report.

Our future financing requirements will depend on many factors, including:

? the timing, scope, progress, results and costs of research and development,

preclinical and non-clinical studies and clinical trials for our current and

? the number, scope and duration of clinical trials required for regulatory

approval of our current and future product candidates;

? the outcome, timing and costs of seeking and obtaining regulatory approvals

from the FDA and comparable foreign regulatory authorities for our product

candidates, including any requirement to conduct additional studies or generate

additional data beyond that which we currently expect would be required to

support a marketing application;

? the costs of manufacturing clinical and commercial supplies of our current and

future product candidates;

? the costs and timing of future commercialization activities, including product

manufacturing, marketing, sales and distribution, for any of our product

candidates for which we receive marketing approval;

? any product liability or other lawsuits related to our product candidates;

? the revenue, if any, received from commercial sales of any product candidates

for which we may receive marketing approval;

? our ability to establish a commercially viable pricing structure and obtain

approval for coverage and adequate reimbursement from third-party and

? the costs to establish, maintain, expand, enforce and defend the scope of our

intellectual property portfolio, including the amount and timing of any

payments we may be required to make, or that we may receive, in connection with

licensing, preparing, filing, prosecuting, defending and enforcing our patents

or other intellectual property rights;

? expenses incurred to attract, hire and retain skilled personnel;

? the costs of operating as a public company; and

? the impact of the COVID-19 pandemic, which may exacerbate the magnitude of the

10,752

Cash Flows Used in Operating Activities

Net cash used in operating activities was $14.2 million and $6.2 million for thethree months ended March 2022 and 2021, respectively.

Cash Flows Used in Investing Activities

Cash Flows from Financing Activities

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JASPER THERAPEUTICS, INC. Management's Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) - Marketscreener.com

Bone Marrow Stem Cells Comments Off on JASPER THERAPEUTICS, INC. Management’s Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) – Marketscreener.com | May 13th, 2022

Aileron Therapeutics, Inc.

Taxanes, such as paclitaxel and docetaxel, cause severe and often permanent chemotherapy-induced hair loss (alopecia)

New non-clinical data demonstrate proof of principle that ALRN-6924 can temporarily arrest the cell cycle in human scalp hair follicles and their stem cells

ALRN-6924-induced cell cycle arrest protected hair follicles from paclitaxel-induced toxicity and irreversible stem cell damage

Ailerons precision medicine-based approach is designed to selectively protect normal, healthy cells from chemotherapy while ensuring chemotherapy cannot protect cancer cells

Ailerons ongoing non-small cell lung cancer (NSCLC) clinical trial and upcoming breast cancer clinical trial will evaluate ALRN-6924s protection against chemotherapy-induced bone marrow toxicities and other side effects, including alopecia

BOSTON, May 10, 2022 (GLOBE NEWSWIRE) -- Aileron Therapeutics (Nasdaq: ALRN), a chemoprotection oncology company that aspires to make chemotherapy safer and thereby more effective to save more patients lives, today announced a late-breaking oral presentation at the upcoming Society for Investigative Dermatology (SID) Annual Meeting, which will be held May 18 21, 2022 in Portland, Oregon. The presentation will highlight new non-clinical data developed in collaboration with Professor Ralf Paus, M.D., DSc, FRSB and his colleagues at the Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery at the University of Miami Miller School of Medicine. This collaboration has generated promising ex vivo data demonstrating that ALRN-6924 protected human hair follicles and their stem cells from chemotherapy-induced acute and permanent damage. Details of the presentation are as follows:

Title:

ALRN-6924, a dual inhibitor of MDMX and MDM2, protects human scalp hair follicles and their epithelial stem cells from paclitaxel-induced toxicity (LB1018)

Presenter:

Jennifer Gherardini, Ph.D.; Paus Laboratory, University of Miami Miller School of Medicine

Date:

Thursday, May 19th

Time:

8:45 AM 11:15 AM PT

Session:

Late-Breaking Abstract Concurrent Session

Chemotherapy-induced toxicities range from severe and life-threatening to those that impact and diminish patients quality of life, sometimes long after chemotherapy has been completed. These toxicities occur because chemotherapy destroys normal, healthy cells while simultaneously destroying cancer cells, said Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer at Aileron. Previously, we showed chemoprotection against severe bone marrow toxicities in small cell lung cancer patients receiving topotecan and demonstrated in healthy volunteers the mechanism of action cell cycle arrest underlying this chemoprotection benefit. We are excited to now present new data that may suggest ALRN-6924s ability to also protect against chemotherapy-induced hair loss, another devastating chemotherapy-induced side effect for millions of cancer patients.

Dr. Paus commented, These results got us quite excited as they directly follow in the footsteps of our prior work that showed arresting the cell cycle can have a strong protective effect against taxane-induced hair follicle damage. Until our research with ALRN-6924, we had not come across a cell cycle arrest-inducing drug that is in clinical testing for protection of normal cells without protecting cancer cells. Thus, ALRN-6924 invites a very promising and completely novel selective protection approach. In addition, we found that ALRN-6924 may exert some additional benefits that could reduce the risk of long-term damage of human hair follicle stem cells by taxanes.

Story continues

Aileron is currently developing ALRN-6924, a first-in-class MDM2/MDMX dual inhibitor, to selectively protect healthy cells in patients with cancers that harbor p53 mutations to reduce or eliminate chemotherapy-induced side effects while preserving chemotherapys attack on cancer cells. ALRN-6924 is designed to activate p53 in normal cells, which in turn upregulates p21, which pauses cell cycle in normal cells but not in p53-mutated cancer cells. The companys vision is to bring chemoprotection to all patients with p53-mutated cancer regardless of the type of cancer or chemotherapy.

About the Findings

Taxanes, such as paclitaxel and docetaxel, are known to cause severe and often permanent chemotherapy-induced alopecia. Over 90% of patients treated with this chemotherapy class experience alopecia, and approximately 10% (paclitaxel) to 25% (docetaxel) of patients experience permanent alopecia. Dr. Paus and his team previously demonstrated that paclitaxel damages human scalp hair follicles by inducing massive mitotic defects and apoptosis in hair matrix keratinocytes as well as bulge stem cell DNA damage, and that pharmacological induction of transient cell cycle arrest can protect hair follicles and stem cells (Purba et al. EMBO Molecular Medicine 2019). Aileron previously conducted in vitro studies showing that ALRN-6924 protected human fibroblasts in cell culture from multiple chemotherapies, but not p53-mutant breast cancer cells.

In the new non-clinical findings to be presented at the SID meeting, when organ-cultured anagen (i.e., active growth phase) scalp hair follicles from two human donors were pre-treated with ALRN-6924 or vehicle (i.e., placebo), followed by paclitaxel or vehicle, ALRN-6924 significantly increased the number of p21-positive hair matrix keratinocytes and bulge stem cells compared to vehicle or paclitaxel alone, confirming cell cycle arrest ex vivo. Further, pretreatment of paclitaxel-treated human hair follicles with ALRN-6924, led to a reduction in the number of melanin clumps, a marker of hair follicle cytotoxicity and dystrophy, as well as a reduction in apoptosis, pathological mitosis, and DNA damage. Aileron believes that these findings support clinical investigation of ALRN-6924 to prevent both acute and permanent chemotherapy-induced alopecia, in addition to its ongoing evaluation of ALRN-6924 to protect against chemotherapy-induced bone marrow and other toxicities.

About Ailerons Clinical Trials of ALRN-6924

Aileron is on track to initiate a Phase 1b randomized, controlled trial of ALRN-6924 in patients with p53-mutated ER+/HER2- neoadjuvant breast cancer in 2Q 2022. The planned breast cancer trial will evaluate ALRN-6924s protection against chemotherapy-induced bone marrow toxicities, as well as other toxicities, including alopecia, in patients with p53-mutated ER+/HER2- breast cancer treated with a doxorubicin plus cyclophosphamide and docetaxel chemotherapy regimen.

The company is currently enrolling patients in a Phase 1b randomized, double-blind, placebo-controlled trial evaluating ALRN-6924s protection against chemotherapy-induced bone marrow and other toxicities in patients with advanced p53-mutated non-small cell lung cancer undergoing treatment with first-line carboplatin plus pemetrexed with or without immunotherapy. While patients in this trial are monitored for alopecia, historically, only a small percentage of patients treated with carboplatin plus pemetrexed experience acute alopecia. Aileron is on track to report interim results on the first 20 patients enrolled in the NSCLC trial in June 2022 and topline results on 60 patients in 4Q 2022.

About Aileron Therapeutics

Aileron is a clinical stage chemoprotection oncology company that aspires to make chemotherapy safer and thereby more effective to save more patients lives. ALRN-6924, our first-in-class MDM2/MDMX dual inhibitor, is designed to activate p53, which in turn upregulates p21, a known inhibitor of the cell replication cycle. ALRN-6924 is the only reported chemoprotective agent in clinical development to employ a biomarker strategy, in which we exclusively focus on treating patients with p53-mutated cancers. Our targeted strategy is designed to selectively protect multiple healthy cell types throughout the body from chemotherapy without protecting cancer cells. As a result, healthy cells are spared from chemotherapeutic destruction while chemotherapy continues to kill cancer cells. By reducing or eliminating multiple chemotherapy-induced side effects, ALRN-6924 may improve patients quality of life and help them better tolerate chemotherapy. Enhanced tolerability may result in fewer dose reductions or delays of chemotherapy and the potential for improved efficacy.

Our vision is to bring chemoprotection to all patients with p53-mutated cancers, which represent approximately 50% of cancer patients, regardless of type of cancer or chemotherapy. Visit us at aileronrx.com to learn more.

Forward-Looking Statements

Statements in this press release about Ailerons future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements about the potential of ALRN-6924 as a chemoprotective agent, including its ability to prevent both acute and permanent chemotherapy-induced alopecia, and the Companys strategy and clinical development plans. The words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, should, target, would and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether Ailerons cash resources will be sufficient to fund its continuing operations for the periods anticipated or with respect to the matters anticipated; whether initial results of clinical trials will be indicative of final results of those trials or results obtained in future clinical trials, including trials in different indications; whether ALRN-6924 will advance through the clinical trial process on a timely basis, or at all; whether the results of such trials will be accepted by and warrant submission for approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether ALRN-6924 will receive approval from regulatory agencies on a timely basis or at all or in which territories or indications ALRN-6924 may receive approval; whether, if ALRN-6924 obtains approval, it will be successfully distributed and marketed; what impact the coronavirus pandemic may have on the timing of our clinical development, clinical supply and our operations; and other factors discussed in the Risk Factors section of Ailerons annual report on Form 10-K for the year ended December 31, 2021, filed on March 28, 2022, and risks described in other filings that Aileron may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Aileron specifically disclaims any obligation to update any forward-looking statement, whether because of new information, future events or otherwise.

Investor Contact:Stern Investor RelationsAlexander Loboalex.lobo@sternir.com

Media Contact:Liz Melone617-256-6622

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SAN DIEGO, Calif., SUZHOU and SHANGHAI, China , May 12, 2022 /PRNewswire/ -- Gracell Biotechnologies Inc. ("Gracell" or the "Company",NASDAQ: GRCL), a global clinical-stage biopharmaceutical company dedicated to developing highly efficacious and affordable cell therapies for the treatment of cancer, today announced the details of three abstracts that it will present at the European Hematology Association 2022 Hybrid Congress (EHA2022 Congress), being held from June 9 June 12 in Vienna, Austria. The abstracts highlight the clinical data from ongoing investigator-initiated trials (IITs) of BCMA/CD19 dual-targeting FasTCAR candidate GC012F in two indications of B-cell non-hodgkin's lymphoma (B-NHL) and relapsed/refractory multiple myeloma (RRMM), and allogeneic TruUCAR candidate GC502 in B-cell acute lymphoblastic leukemia (B-ALL).

"We are very excited to share our data for both our FasTCAR candidate GC012F in two indications of RRMM and B-NHL, and allogeneic TruUCAR candidate GC502 in B-ALL at the EHA2022 Congress," said Dr. Martina Sersch, Chief Medical Officer of Gracell. "The new data, including the expanded indication of GC012F into B-NHL, demonstrates the potential of our platforms and provides further validation. The clinical data of BCMA/CD19 dual-targeting GC012F in the treatment of B-NHL shows promising early results, along with benefits of the next-day manufacturing enabled by the FasTCAR platform. The CD19/CD7 dual-directed CAR-T therapy GC502 is our second allogeneic candidate on our TruUCAR platform, demonstrating the potential wide applicability of the TruUCAR design."

BCMA/CD19 Dual-Targeting FasTCAR-T GC012F for the Treatment of B-NHL

GC012F is an autologous CAR-T therapeutic candidate dual-targeting B cell maturation antigen (BCMA) and CD19. It is developed using Gracell's proprietary FasTCAR platform which enables next-day manufacturing, and is currently being evaluated in IITs in China including in RRMM and B-NHL. GC012F is the first BCMA/CD19 dual-targeting CAR-T in human trials for B-NHL.

Gracell will present the early results of the first-in-human phase 1 IIT in China evaluating the safety and tolerability of GC012F in B-NHL patients. Three patients who had received a median of two prior lines of therapy were enrolled, all of which presented with bulky disease. As of the February 22, 2022 data cutoff date, the enrolled patients had received one single infusion of GC012F at three different doses of 3.7x104 cells/kg and 2-3x105 cells/kg.

All three patients had achieved a complete response (CR) confirmed by PET- CT at day 28 after GC012F infusion. At 3-month follow-up, both of the two assessable patients had ongoing response. No dose-limiting toxicities were observed and no immune effector cell-associated neurotoxicity syndrome (ICANS) were observed. CRS presented as Grade 1 in two patients and Grade 3 in one patient (duration of two days) with no Grade 4 or 5 events.

Details of the presentation are as follows:

BCMA/CD19 Dual-Targeting FasTCAR-T GC012F for the Treatment of RRMM

Gracell will also present as an oral abstract presentation the updated results from the first-in-human IIT evaluating GC012F for the treatment of RRMM patients. This data is currently under embargo and will be published on the EHA2022 Hybrid Congress website on Thursday, May 26 concurrently with ASCO.

Details of the presentation are as follows:

CD19/CD7 Dual-directed Allogeneic TruUCAR-T GC502 for the Treatment of B-ALL

GC502 leverages the novel dual-directed CAR design of Gracell's proprietary TruUCAR platform, designed to generate high-quality allogeneic CAR-T cell therapies that can be administered "off-the-shelf" at lower cost and with faster patient's access. TruUCAR-enabled GC502 utilizes the dual-directed CAR design with one CAR targeting CD19 on malignant cells and a second CAR targeting CD7 to suppress host-versus-graft rejection. An enhancer molecule is embedded in the basic construct of TruUCAR to enhance proliferation of TruUCAR T cells.

Between September 2021 and January 2022, four r/r B-ALL patients were enrolled and treated in an open-label, non-randomized, prospective IIT in China in two different dose levels and with two different formulations. Patients were heavily pretreated, and all had previously received either autologous or donor derived CD19 or CD19/CD22 targeted CAR-T therapy. As of the January 28, 2022 data cutoff date, all four patients had received a single dose of GC502, including one patient at dose level 1 (DL1) 1.0x107 cells/kg and three patients at dose level 2 (DL2) 1.5x107 cells/kg. Patients received a Flu/Cy based lymphodepletion regimen prior to treatment with GC502.

Three of four patients achieved minimal residual disease negative complete response or complete response with incomplete count recovery (MRD- CR/CRi), and one patient achieved a partial response at month one and subsequently received allogeneic hematopoietic stem-cell transplantation (allo-HSCT) on day 39.

Cytokine release syndrome (CRS) presented as Grade 2 and Grade 3 with no Grade 4 or 5 events. No immune effector cell-associated neurotoxicity syndrome (ICANS) or acute graft-versus-host disease (aGvHD) were observed.

Details of the presentation are as follows:

For more information about the EHA2022 Hybrid Congress, visit http://www.ehaweb.org.

About GC012F

GC012F is a FasTCAR-enabled dual-targeting CAR-T product candidate that is currently being evaluated in IIT studies in China for the treatment of multiple myeloma and B-cell non-Hodgkin's lymphoma. GC012F simultaneously targets CD19 and BCMA to drive fast, deep and durable responses, which can potentially improve efficacy and reduce relapse in multiple myeloma and B-NHL patients.

About B-NHL

Non-Hodgkin's lymphoma (NHL) is a group of blood cancers that developed from lymphocytes, most commonly derived from B cells (B-NHL). Globally, approximately 510,000 patients are diagnosed with NHL every year with about 80,470 patients expected to be diagnosed with NHL in the United States in 2022[1]. B-NHL accounts for approximately 85% of NHL diagnoses.

[1] Data source: American Cancer Society

About GC502

GC502 is a TruUCAR-enabled CD19/CD7 dual-directed, off-the-shelf allogeneic CAR-T product candidate that is being studied in an ongoing Phase 1 IIT in China for the treatment of B-cell malignancies. GC502 is manufactured using T cells from non-human leukocyte antigen (HLA) matched healthy donors. An enhancer molecule is embedded in the basic construct of TruUCAR to enhance proliferation of TruUCAR T cells. Optimized for CD19/CD7 dual-CAR functionality and in vivo durability, GC502 has demonstrated robust anti-tumor effects with potential to suppress host versus graft (HvG) rejection in preclinical models.

About B-ALL

Acute lymphoblastic leukemia (ALL) is a type of blood cancer characterized by proliferation of immature lymphocytes in the bone marrow, which can involve either T lymphocytes (T-ALL), or B lymphocytes (B-ALL). Globally, approximately 64,000 patients are diagnosed with ALL every year with an estimated 6,660 new cases to be diagnosed in the United States in 2022[2]. B-ALL accounts for 75% of ALL diagnoses in adults.

[2] Data source: American Cancer Society

About FasTCAR

CAR-T cells manufactured on Gracell's proprietary FasTCAR platform appear younger, less exhausted and show enhanced proliferation, persistence, bone marrow migration and tumor cell clearance activities as demonstrated in preclinical studies. With next day manufacturing, FasTCAR is able to significantly improve cell production efficiency which may result in meaningful cost savings, and, together with fast turnaround time, enables enhanced accessibility of cell therapies for cancer patients.

About TruUCAR

TruUCAR is Gracell's proprietary technology platform and is designed to generate CAR-T cell therapies from high quality allogeneic T cells that can be administered "off-the-shelf" at lower cost and with improved accessibility of cell therapies for cancer patients. With differentiated design enabled by gene editing, TruUCAR is designed to control HvG as well as GvHD without the need for being co-administered with additional strong immunosuppressant after conventional lymphodepletion. The novel dual-CAR design allows tumor antigen-CAR moiety to target malignant cells, while the CD7 CAR moiety is designed to suppress rejection (HvG response) of allogeneic CAR-T cells by host T and NK cells (HvG).

About Gracell

Gracell Biotechnologies Inc.("Gracell") is a global clinical-stage biopharmaceutical company dedicated to discovering and developing breakthrough cell therapies. Leveraging its pioneering FasTCAR and TruUCAR technology platforms and SMART CARTMtechnology module, Gracell is developing a rich clinical-stage pipeline of multiple autologous and allogeneic product candidates with the potential to overcome major industry challenges that persist with conventional CAR-T therapies, including lengthy manufacturing time, suboptimal cell quality, high therapy cost, and lack of effective CAR-T therapies for solid tumors. For more information on Gracell, please visit http://www.gracellbio.com.Follow @GracellBio on LinkedIn.

Cautionary Noted Regarding Forward-Looking Statements

Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements" within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the expected trading commencement and closing date of the offering. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including factors discussed in the section entitled "Risk Factors" in Gracell's most recent annual report on Form 20-F as well as discussions of potential risks, uncertainties, and other important factors in Gracell's subsequent filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Gracell specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. Readers should not rely upon the information on this page as current or accurate after its publication date.

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Dr. Sara Vasconcelos in the laboratory at Toronto General Hospital on May 11.Christopher Katsarov/The Globe and Mail

When Sara Vasconcelos talks about her work, it sounds as if shes in the restoration business. But instead of repairing damaged buildings, the researcher at Torontos University Health Network wants to fix damaged hearts by using stem cells to rebuild cardiovascular tissue.

Now, Dr. Vasconcelos is one step closer to achieving that goal with a $3-million grant from the Stem Cell Network, a Canadian research funding organization. Her effort is one of 32 projects across the country that rose to the top in a competition for in the largest outlay of federal funding for regenerative medicine in 20 years.

On Thursday, the Ottawa-based network announced a total of $19.5-million in awards, which together with matching funds from various partners, will translate into $42-million for research and clinical trials over the next three years. The funding will enable the work of more than 400 scientists, clinicians and trainees, the organization said.

Its a big step, said Dr. Vasconcelos, who said she will use her award to build on preliminary findings obtained using rats. She will next work with pig hearts, which offer a much closer analogue to the human organ.

While doing so, she also hopes to overcome a barrier that has stood in the path of those who are trying to repair hearts using cardiomyocytes heart tissue cells that are grown from embryonic stem cells. The problem is that the replacement cells wither away if they are not nourished and kept alive by blood vessels.

As part of her project Dr. Vasconcelos aims to use a technique in which small sections of microscopic blood vessels are harvested from human fat and implanted along with the heart cells.

The microvessels that are like Lego pieces, she said. You can put a whole bunch of them in with the stem cell-derived cardiomyocytes and they will connect to each other and connect to the host vessels that carry blood.

With her grant secured, Dr. Vasconcelos said she is assembling the team that will test the method on pig hearts later this year. Ultimately, her goal is to develop the technique into a therapy that can restore cardiac function in human patients following a heart attack, she said.

Among the other projects to win funding are some that are already heading for clinical studies. That includes a large study led by Guy Sauvageau, a hematologist at Maisonneuve-Rosemont Hospital in Montreal, that involves developing engineered blood stem cells to treat leukemia.

Working with a group of clinical sites in the U.S., Dr. Sauvageau and his team have already had success at treating patients with leukemia who relapse. The new project will involve introducing genetical engineered stem cells into people who are better able to withstand cancer treatment and facilitate recovery.

Between 10,000 and 20,000 patients a year would benefit from this kind of therapy, Dr. Sauvageau said.

In the future, he added, the study could open the door to teaching the body to continually produce and replenish its own cancer-killing immune cells rather than having those cells created externally and infused in a form of treatment know as CAR T-cell therapy.

As part of another of the funded projects, David Thompson at the Vancouver Coastal Health Research Institute will conduct clinical trials for one of the worlds first genetically engineered cell replacement therapies for type 1 diabetes.

Dr. Sara Vasconcelos points to an image of vascular tissue in the laboratory at Toronto General Hospital where they engineer cell and tissue regeneration.Christopher Katsarov/The Globe and Mail

The diversity of the projects highlights the increasing prominence of stem cells in multiple domains of health research, an area where Canada has a long track record of success ever since University of Toronto researchers James Till and Ernest McCullough established the existence of stem cells cells which can differentiate into more specialized types in bone marrow in 1961.

Tania Bubela, dean of health sciences at Simon Fraser University in Burnaby, B.C., said the kind of funding the Stem Cell Network provides helps bridge a crucial gap between fundamental laboratory research and proven therapies for patients.

What weve realized over time is that where you get public sector investments to close the funding gap is exactly in that translational space from preclinical into early stage clinical trials, Dr. Bubela said. Once you have that proof that things are going to work and that they can be taken up by the health system, thats when venture capital starts to get interested.

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Lab animalshave been an essential part of life-altering and lifesaving scientific research and discovery. But a growing number of scientists are calling for an end to their use, and pushing for new methods that can better replicate human biology instead.

Among them is biomedical researcher Dr. Charu Chandrasekera. She'sthe founder and executive director of the Canadian Centre for Alternatives to Animal Methods at the University of Windsor. Here is part of her conversation with Quirks & Quarks host Bob McDonald.

Animal testing historically has been considered a regrettable necessity in the quest to save human lives. Why do you think this is not the case?

Animals have played an integral role in science over the past century or more, to the point where we have made them the gold standard for human biology. And therein lies the problem.

Over 90 per centof drugs tested to be safe and effective in animals, fail in human clinical trials. And even the ones that make it through, they can still be withdrawn or receiveblack box warnings due to unpredicted side effects in humans. And it's not just the drugs that fail, but the drugs that we missed,like the drugs that never made it to human clinical trials because they had some irrelevant side effects in animals. They could very well been safe in humans.So we've likely missed out on many life saving, history altering medications.

Why would a drug work in an animal but not in a human?

Well, there's a very simple answer to that. We humans, we are not 70-kilogram versionsof mice, rats, guinea pigs, rabbits, cats, dogs, sheep or monkeys. We're human. We're separated by hundreds of millions of years of evolution from some of these laboratory animal species.

And it's not only just the species' differences, but there are also so many issues with the way we conduct this research. We have to induce disease by either doing surgical modifications, giving them a high-fat diet. So dietary modifications, genetic modifications, take out a gene, put in a gene, or chemically destroy their pancreas, for example, to create diabetic models. So when you're doing these experimental modifications in these animals, you're really not recreating the human disease. You are creating a version of a human disease.

What motivated you to go from doing animal research in your lab to trying to end the practice altogether?

It was the scientific failures combined with the ethical standards that I was not happy with. So I worked with animal models of heart failure. And while I was doing all these studies, my dad actually had a heart attack and he required quadruple bypass surgery. And while I was with him at the Halifax Heart Centre, I thought to myself, is the research that I'm doing going to truly help humans like my father and everybody else in this ward?

A few weeks later, when I came back to the lab, I ran into this veteran cardiovascular researcher, and he had worked on receptors similar to the ones that I was working on. And I just looked at him and I said, "Do you think these receptors were activated in my dad's heart during his heart attack?" And his response was, "How the hell would I know? We've never looked at this in the human heart."And for me, that day, it was a profound realization. It was almost like an epiphany. What am I doing this for?

Those are the reasons why we should end animal research. Let's explore some of the solutions. What are some of the alternative methods to animals in research that are being developed?

Recreating human biology in a petri dish is no easy feat. There's no single magical method that can replace all animal testing tomorrow morning. It's really all about context of use, fit for purpose. What is the biological question you're trying to answer, and in what context, and how best can we address that?

So we can use human cells and tissues from cadavers and surgical remains. We can take a diseased heart removed during transplant surgery and bring it back to life in the lab, make it beat again, infused with drugs to study cardiac physiology and cardiac toxicity. We can take just a single human cell and obtain hundreds of data points on human DNA and RNA through multiomics studies. We can engineer human tissue, create miniature organ models like organoids to recapitulated complex diseases using stem cell technologies. The field is just exploding.

Can you give me a list of some of the projects that you're working on at your centreright now?

We currently have liver, gut, kidney, lung and blood brain barrier models in development. And we have a number of projects that incorporate these tissues in different configurations to create disease in a dish, and toxicity on a chip. One of the first disease models we're creating is diabetes in a dish, and we're also doing Alzheimer's in a dish. We actually have a project designed specifically to reduce and replace toxicity testing in dogs. And we even have an eco-toxicology project where we're using fish lines to replace toxicity testing on live fish.

This is all based on evidence now. So for some of these methods that we have, we are already seeing that they are able to recapitulate these human responses. We can actually look at the data that we get from using these new technologies and compare them against existing data. But we are also seeing things like new data where we're going back and reevaluating these old drugs that failed in one system and then putting them through a human biology based system. And we're seeing that they are able to predict human biology better.

How hopeful are you that we can make this shift away from using animals in scientific research?

I'm actually very hopeful that we will be able to shift away from this animal-centred paradigm to one where human biology is the gold standard and humans are the quintessential animal model. There are scientific, innovative financial and legislative efforts happening around the world to make this happen.

The goal really is to reduce as much as possible at this point. And even if we needed to use animals, could they become the last resort that you are only using, you know, five rats, for example, for a procedure that required 400 rats before?So because of all of these efforts happening globally, I'm very hopeful.

Produced by Amanda Buckiewicz. This interview has been edited for length and clarity.

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As previously reported by BioSpace, a group of scientists from The Babraham Institutein the United Kingdom was able to successfully rejuvenate skin cells by a full 30 years.

The research team published a study in eLife Sciences last month describing their process of using induced pluripotent stem cell (iPSC) reprogramming to reverse aging effects at the cellular level.

Study co-author Ins Milagre told BioSpace that the research process was a team effort. In Lead Author Wolf Reiks lab, she was working on cell reprogramming while a colleague focused on the epigenetic clock.

Milagre came into her research career driven by an early interest in biology. I was fascinated by biology all of my life. I had a very good biology teacher when I was in high school, she said.

She explained that she was also a huge fan of the drama series The X-Files, seeing Gillian Anderson's character, Dana Scully, as a role model. I thought that being a scientist must be very cool. This combination made me decide to go into biology.

The research teams original hypothesis came from knowing that we can easily program cells to be zero years of age. No matter what age they are in the beginning, the cells normally reprogram back to embryonic age, or zero years of age.

Though reprogrammed embryonic cells are free of gradual aging decline, they lack identity and thus function. The research team began to consider what would happen if they could get the cells to only partially rejuvenate.

With embryonic cells, downstream applications can be a problem. We thought that maybe we could just rejuvenate the cells and then coax them back into being the cell of origin, Milagre explained. At first, the idea was casually discussed over happy hour, but then the team found that preliminary experiments yielded promising results.

They utilized Yamanaka factors (Oct4, Sox2, Klf4, c-Myc), which are typically used to differentiate cells into the embryonic stem cell stage. Instead of allowing the full time that it takes for cells to get to the embryonic life stage, we decided to stop the reprogramming process halfway through, Milagre said.

By doing this, we were able to get the cells to a younger age. They were easily reverted back to the original cell type, which in our case, were skin cells. Pausing the process in the middle allowed the cells to become a younger version of the same cell type. The researchers named the novel method maturation phase transient reprogramming (MPTR).

What I find very exciting about this study is that we showed that it's possible to rejuvenate cells, she said. Though the Yamanaka factors have been used in other labs, the Babraham Institute team was the first to rejuvenate cells by a full 30 years.

Courtesy of the Babraham Institute

The scientists observed several benefits of the functionally younger cells. The skin cells were better able to produce collagen, and they were responding better to wound healing sites, Milagre said. The above photo depicts the collagen levels of the skin cells before and after rejuvenation. On the left are the original 53-year-old skin cells, and on the right are the reprogrammed cells. The collagen levels are depicted in red.

Milagre noted that the study is very preliminary, with much more research to be completed before the technology is safe and available. We only tested this in skin cells, so we don't know if this is also possible in other cell types, though we believe that it probably is based on similar work from other groups.

Another element that must be studied is how the technology will work without using the same viral vectors. We need to make a safer technology to do this. As a proof of principle, we showed that it's possible to rejuvenate cells by 30 years. Now, we need to do more research to be able to eventually move this technology into a more clinical setting.

Once the technology is safe and ready, Milagre noted that many downstream applications could be possible. We can think about trying to tackle neurodegenerative and degenerative disorders as well as ameliorating some aging effects. If we can get cells to be functionally younger, even if we don't expand peoples lives, we might be able to give people a better quality of life.

Reik explained in an earlier article that the findings could eventually lead to targeting specific genes that would be able to rejuvenate without any reprogramming. Milagre said that Yamanaka factors are working as pioneers that can start new gene expression programs. If we understand which genes are being activated downstream, we can eventually think about modulating these genes. We can try switching on a minimum number of effector genes. This would be a way to overcome using viral vectors.

Though potential future benefits of the findings are a long way off, the team is still considering the people they may help down the line. We hope the technology will help people live better lives without diseases, or without the consequences of a disease even if they still have it, Milagre said.

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Scientists Rejuvenate Skin Cells by 30 Years, with Pioneering Potential - BioSpace

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Saahil Joshi, age 17, Crystal Springs Uplands School, Hillsborough, Calif.: Too Many Cooks Spoil the Broth: The Science and Future of Drug-Drug Interactions

Micah: Salt: The Sapid and Sophisticated Seasoning

Katherine Kricorian, age 17, Santa Susana High School, Simi Valley, Calif.: From Algae to Energy: A Blooming Solution to Pollution

Chloe Lee, age 14, Korea International School Pangyo Campus, Gyeonggi-do, Korea: Do Plants Have Feelings?

Seungjae (Andy) Lee, age 13, Hong Kong International School, Tai Tam, Hong Kong: Keeping Your Pet Friend Forever: Is Cloning a Soul Possible?

Zhuocheng Li, age 16, Green Hope High School, Cary, N.C.: The Blood That Saved Countless Lives

Andrew C. Lin, age 12, Visions in Education Homeschool Academy, Carmichael, Calif.: Breaking the Speech Barrier

Andy Lu, age 16, Desert Vista High School, Phoenix: Hypersonic Flight: Can We Go Faster?

Camille: Sugar and the Body: A Bittersweet Relationship

Natalia Meza, age 17, American School of Madrid, Madrid: What Happens in Vagus, Stays in Vagus?

Aman Mistry, age 17, Smithtown High School, East Saint James, N.Y.: Helping a Blind Man See: The Miracle of Optogenetics

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Lasers, Fish-Skin Bandages and Pain-Free Vaccines: The Winners of Our 3rd Annual STEM Writing Contest - The New York Times

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We all love trying out new skincare products that give our skin that supple plump and glow. Many of us also use anti-ageing and skin firming products to help reduce those stubborn wrinkles, pigmentation and fine lines. Ever heard the saying, An apple a day, keeps the doctor away? Now, what if we told you that this apple can help your skin without you actually having to eat it? Got you wondering how now, did we?Until several years ago, the tart, unappealing variant of the Swiss-grown Uttwiler Sptlauber apples, wasnt proving to add any value in terms of offering. This was until some scientists discovered the unusual longevity of the stem cells that kept these apples alive months after other apples shriveled and fell off their trees. What are stem cells, you ask? Stem cells are extremely unique in a way that they have the ability to go through numerous cycles and cell divisions while maintaining the undifferentiated state. Essentially, stem cells are capable of self-renewal and can transform themselves into other cell types of the same tissue. One of their primary roles is to replenish dying cells and regenerate damaged tissue. Stem cells provide the ability for species to renew and repair themselves. Plants are rooted in the ground and have to survive extreme weather changes, therefore their stem cells contain much stronger antioxidant contents than those of humans cells.

But how does this help your skin? Heres a list of the goodness that Swiss apple stem cells can have on your skin.

The high antioxidant found in plant stem cells supports the skin in combating free radicals that would otherwise cause skin damage. They give your skin the tools to protect itself, offering immense anti-ageing and anti-inflammatory benefits. The boost of antioxidants and amino acids helps boost collagen production and keeps your skin radiant and youthful.

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Have you heard of the goodness of Swiss apple stem cells? - Times of India

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If you are a new or expectant parent, youve probably heard about the option of banking your babys cord blood at birth. The topic can be confusing, and you may have many unanswered questions.

You may be unsure exactly what cord banking involves, why people choose to bank their infants blood, whether its worth it to do so, and how much it costs to bank cord blood.

Heres a simple breakdown of the potential benefits of cord blood banking and how to decide if its right for your family.

At birth, your newborns placenta and umbilical cord contain blood that is rich with potentially lifesaving stem cells. This blood can be removed, stored, and used down the road to treat various diseases and conditions.

Healthcare professionals do not remove cord blood directly from babies or birthing parents. Rather, it comes from the umbilical cord and placenta themselves, according to the American College of Obstetricians and Gynecologists (ACOG).

The stem cells in umbilical cords and placentas are called hematopoietic stem cells. In people with certain health conditions, they can be used to produce healthy new cells and replace damaged cells.

Stem cells are used to treat over 70 types of diseases, according to ACOG. These include:

You might choose to bank your newborns cord blood for several reasons.

First, you may choose to do so if you have a family member with a medical condition that might benefit from stem cell donation. Alternatively, you might want to donate your babys blood to help another person in need of stem cells.

One myth about cord banking is that you child can use the cord blood down the line, should they develop a serious medical concern. This type of transfer where a persons own cord blood is used to treat their health condition is called an autologous transplant.

ACOG notes that autologous transfers are rare.

If your child has a genetic disease, for example, treating them with their own stem cells wouldnt help because these stem cells contain the same genes as the cells that are involved in the disease. Similarly, your own childs stem cells cant be used to treat cancers such as leukemia.

Instead, most cord blood transplants are allogeneic.

This means that your childs stem cells would be used to treat another child or adult. It would require a strong match between the stem cell recipient (the person using the stem cells) and the stem cell donor (your child).

The benefits of cord blood banking depend on your purpose and where you are storing your childs cord blood.

If you are storing your childs blood at a private institution, you may be able to use the stem cells to directly benefit a family member in need, including a close family member or your childs sibling.

Storing your babys cord blood in a public facility has benefits, too. Stem cells can help treat people with many types of health conditions, including cancers and certain metabolic and immunologic conditions, according to the Health Resources & Services Administration.

There are many advantages to using stem cell transplants for treating medical conditions rather than using bone marrow transplants.

According to ACOG, these benefits include:

If you want to have your newborns cord blood collected, you should inform your OB-GYN or birthing professional, such as a midwife, and the hospital or facility where you will give birth. They may need to order special equipment or a cord collecting kit.

Usually, you will need to inform your healthcare team of your choice to bank your infants blood about 6 weeks in advance of your due date. Youll also need to be sure youve signed all the required consent forms.

Cord blood extraction happens in the hospital after birth and after a healthcare professional has clamped and cut the umbilical cord. They will then use a needle to draw blood out of the cord and store in a designated bag.

The entire process is quick about 10 minutes and does not involve direct contact with your baby.

Sometimes, cord blood extraction isnt possible. Reasons for this may include:

After collection, cord blood must be stored very carefully to ensure that its quality is preserved. Each facility has its own protocols and procedures for how this is done.

The Academy of American Pediatrics (AAP) explains certain accrediting institutions oversee the regulation of cord blood storage and cautions that some private cord blood banks may not meet all these standards.

Before agreeing to have your childs cord blood stored at a private facility, you may want to find out:

Cord blood bank accrediting institutions include:

Before considering cord blood donation, its important for you to understand the difference between private and public banks. Heres what to know:

Private banks are usually used by parents who believe that their childs cord blood may be helpful to a family member who has a medical condition.

They require you to pay on an ongoing basis for your childs cord blood to be stored.

Not all private banks are accredited or regulated in the same way that public banks are.

Public banks are free and supported by government or private funds.

Currently, there is very little evidence that storing your childs blood will help your own child fight a medical condition in the future. In fact, if your child needs stem cells to treat a condition, its more likely that they will receive a donation from a public cord bank.

When you donate to a public cord bank, you do not get to decide who will use your childs blood. You are essentially donating your childs cord blood to help a person in need.

Public cord banks are heavily regulated, and cord blood from these banks is used more frequently than cord blood from private banks. In fact, blood from public banks is used 30 times more frequently than from private banks.

Most major health organizations including the Academy of American Pediatrics and the American College of Obstetricians and Gynecologists recommend public cord blood banking.

Another reason these organizations recommend using public cord blood banks is that they are consistently and well regulated.

Cord blood banking at a public cord bank is free, and you will not have to pay any costs if you donate. These institutions are usually supported by federal funds or receive private funding.

On the other hand, private blood cord banks charge fees, and you must pay these fees for the entire time your childs cord blood is stored in these facilities.

Private cord banks generally charge an initial fee for collecting and processing cord blood. After these initial fees, you will also pay annual fees for ongoing storage. Private cord blood banks vary in their fee amounts, but they average about $2,000 for initial fees and between $100 and $175 each year for annual storage fees, per the AAP.

There are many benefits to banking cord blood. But how you do it depends on several factors, including your familys medical needs and your financial situation.

Almost anyone can choose to donate their infants cord blood to a public bank. Doing so may help many people. While most medical institutions do not recommend private cord banking, this may be the right choice for you if you have a family member who might use the cord blood you bank to treat a health condition.

Either way, its a good idea to speak with your healthcare professional before deciding on whether to bank your babys cord blood. They can also advise you on the best way to do it and which type of blood bank may best meet your needs.

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Cord Blood Banking: Benefits, Cost, and Process - Healthline

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In 1996, Dolly the sheep made headlines around the world after becoming the first mammal to be successfully cloned from an adult cell. Many commentators thought this would catalyze a golden age of cloning, with numerous voices speculating that the first human clone must surely be just a few years away.

Some people suggested that human clones could play a role in eradicating genetic diseases, while others considered that the cloning process could, eventually, eliminate birth defects (despite research by a group of French scientists in 1999 finding that cloning may actually increase the risk of birth defects).

There have been various claims all unfounded, it is important to add of successful human cloning progams since the success of Dolly. In 2002, Brigitte Boisselier, a French chemist and devout supporter of Ralism a UFO religion based on the idea that aliens created humanity claimed that she and a team of scientists had successfully delivered the first cloned human, whom she named Eve.

However, Boisselier was unwilling or indeed unable to provide any evidence, and so it is widely believed to be a hoax.

So why, almost 30 years on from Dolly, haven't humans been cloned yet? Is it primarily for ethical reasons, are there technological barriers, or is it simply not worth doing?

Related: What are the alternatives to animal testing?

"Cloning" is a broad term, given it can be used to describe a range of processes and approaches, but the aim is always to produce "genetically identical copies of a biological entity," according to the National Human Genome Research Institute (NHGRI).

Any attempted human cloning would most likely utilize "reproductive cloning" techniques an approach in which a "mature somatic cell," most probably a skin cell, would be used, according to NHGRI. The DNA extracted from this cell would be placed into the egg cell of a donor that has "had its own DNA-containing nucleus removed."

The egg would then begin to develop in a test tube before being "implanted into the womb of an adult female," according to NHGRI.

However, while scientists have cloned many mammals, including cattle, goats, rabbits and cats, humans have not made the list.

"I think there is no good reason to make [human] clones," Hank Greely, a professor of law and genetics at Stanford University who specializes in ethical, legal and social issues arising from advances in the biosciences, told Live Science in an email.

"Human cloning is a particularly dramatic action, and was one of the topics that helped launch American bioethics," Greely added.

The ethical concerns around human cloning are many and varied. According to Britannica, the potential issues encompass "psychological, social and physiological risks." These include the idea that cloning could lead to a "very high likelihood" of loss of life, as well as concerns around cloning being used by supporters of eugenics. Furthermore, according to Britannica, cloning could be deemed to violate "principles of human dignity, freedom and equality."

In addition, the cloning of mammals has historically resulted in extremely high rates of death and developmental abnormalities in the clones, Live Science previously reported.

Another core issue with human cloning is that, rather than creating a carbon copy of the original person, it would produce an individual with their own thoughts and opinions.

"We've all known clones identical twins are clones of each other and thus we all know that clones aren't the same person," Greely explained.

A human clone, Greely continued, would only have the same genetic makeup as someone else they would not share other things such as personality, morals or sense of humor: these would be unique to both parties.

People are, as we well know, far more than simply a product of their DNA. While it is possible to reproduce genetic material, it is not possible to exactly replicate living environments, create an identical upbringing, or have two people encounter the same life experiences.

So, if scientists were to clone a human, would there be any benefits, scientific or otherwise?

"There are none that we should be willing to consider," Greely said, emphasizing that the ethical concerns would be impossible to overlook.

However, if moral considerations were removed entirely from the equation, then "one theoretical benefit would be to create genetically identical humans for research purposes," Greely said, though he was keen to reaffirm his view that this should be thought of as "an ethical non-starter."

Greely also stated that, regardless of his own personal opinion, some of the potential benefits associated with cloning humans have, to a certain degree, been made redundant by other scientific developments.

"The idea of using cloned embryos for purposes other than making babies, for example producing human embryonic stem cells identical to a donor's cells, was widely discussed in the early 2000s," he said, but this line of research became irrelevant and has subsequently not been expanded upon post-2006, the year so-called induced pluripotent stem cells (iPSCs) were discovered. These are "adult" cells that have been reprogrammed to resemble cells in early development.

Shinya Yamanaka, a Japanese stem cell researcher and 2012 Nobel Prize winner, made the discovery when he "worked out how to return adult mouse cells to an embryonic-like state using just four genetic factors," according to an article in Nature. The following year, Yamanaka, alongside renowned American biologist James Thompson, managed to do the same with human cells.

When iPSCs are "reprogrammed back into an embryonic-like pluripotent state," they enable the "development of an unlimited source of any type of human cell needed for therapeutic purposes," according to the Center of Regenerative Medicine and Stem Cell Research at the University of California, Los Angeles.

Therefore, instead of using embryos, "we can effectively do the same thing with skin cells," Greely said.

This development in iPSC technology essentially rendered the concept of using cloned embryos both unnecessary and scientifically inferior.

Related: What is the most genetically diverse species?

Nowadays, iPSCs can be used for research in disease modeling, medicinal drug discovery and regenerative medicine, according to a 2015 paper published in the journal Frontiers in Cell and Developmental Biology.

Additionally, Greely also suggested that human cloning may simply no longer be a "sexy" area of scientific study, which could also explain why it has seen very little development in recent years.

He pointed out that human germline genome editing is now a more interesting topic in the public's mind, with many curious about the concept of creating "super babies," for example. Germline editing, or germline engineering, is a process, or series of processes, that create permanent changes to an individuals genome. These alterations, when introduced effectively, become heritable, meaning they will be handed down from parent to child.

Such editing is controversial and yet to be fully understood. In 2018, the Council of Europe Committee on Bioethics, which represents 47 European states, released a statement saying that "ethics and human rights must guide any use of genome editing technologies in human beings," adding that "the application of genome editing technologies to human embryos raises many ethical, social and safety issues, particularly from any modification of the human genome which could be passed on to future generations."

However, the council also noted that there is "strong support" for using such engineering and editing technologies to better understand "the causes of diseases and their future treatment," noting that they offer "considerable potential for research in this field and to improve human health."

George Church, a geneticist and molecular engineer at Harvard University, supports Greely's assertion that germline editing is likely to garner more scientific interest in the future, especially when compared with "conventional" cloning.

"Cloning-based germline editing is typically more precise, can involve more genes, and has more efficient delivery to all cells than somatic genome editing," he told Live Science.

However, Church was keen to urge caution, and admitted that such editing has not yet been mastered.

"Potential drawbacks to address include safety, efficacy and equitable access for all," he concluded.

Originally published on Live Science.

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Why haven't we cloned a human yet? - Livescience.com

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image:A team at Scripps Research demonstrated how protein-sugar clusters called proteoglycans can guide processes like cell maturation and neuronal synapse formation, among other functions. As one example, pictured, semi-synthetic syndecan-1 proteoglycan rescues the maturation of mouse embryonic stem cells into neural precursor cells (red and green). view more

Credit: Meg Critcher, Scripps Research

LA JOLLA, CAScientists at Scripps Research have developed a set of methods for the closer study of one of the least-accessible, least-understood players in biology: protein-sugar conjugates called proteoglycans.

These molecules are often thickly present on the surfaces of cells and are known to have a broad set of functions in the body, though how they work and how their dysfunctions contribute to diseases are largely mysteries.

The scientists, who report their work in Nature Chemical Biology on May 12, 2022, devised synthetic proteoglycans that closely mimic real ones but have convenient chemical handles for modifying them. These and other aspects of their research platform enable the systematic study of how proteoglycans structure affects their functions in health and disease. The scientists demonstrated the effectiveness of their platform by using it to make new discoveries about proteoglycans roles in early cell development and in cancer cell spreading.

Were essentially unpacking the complexity of these molecules by constructing them in a modular way ourselves, and studying them in a tightly controlled environment, says study senior author Mia Huang, PhD, associate professor in the Department of Molecular Medicine at Scripps Research.

A proteoglycan starts as just a proteinthe so-called core proteinbut this protein contains special sites where any of a variety of sugar-related molecular chains called glycosaminoglycans (GAGs) can be linked. Within the cell where the protein originates, enzymes catalyze the attachment of GAGs to it, and this newborn proteoglycan normally is further decorated with clusters of sulfur and oxygen atoms called sulfates. The finished proteoglycan may be anchored into the cell membrane, its GAG chains waving in the extracellular fluid like seagrass, or it may be secreted from the cell to perform other functions.

With such complexity, it is no surprise that proteoglycans have versatile functionsthey are present in virtually all tissues, including cartilage, collagen, bone, skin, blood vessels, brain cells and mucosal surfaces. They help steer processes such as cell maturation, cell adhesion, cell migration, and neuronal synapse formation; serve as receptors for protein signaling partners; and are even used by some viruses and bacteria to latch onto cells. But proteoglycans complexity also means that how they do what they do, and with what partners, remains largely undiscovered. Scientists arent even certain how many proteoglycans there are in human and other mammalian cellsalthough there are at least dozens.

Huang and her team, including first authors Timothy OLeary, PhD and Meg Critcher, respectively a postdoctoral researcher and doctoral candidate in the Huang Lab during the study, constructed proteoglycan core proteins that are almost identical to known core proteins, but contain special molecular handles enabling the researchers to change the numbers and locations and types of GAG chains that bind to them. This allows the researchers to study systematically how the function of a proteoglycan changes as its GAG arrangement changes.

The researchers also developed techniques allowing them to anchor their proteoglycans in cell membranes or to let them float freely, to see how this affects proteoglycans functions in different circumstances.

Using their synthetic versions of common proteoglycans called syndecans, the scientists were able to study the respective contributions of GAG chains and core proteins. Specifically, they looked at two key biological processes mediated by syndecans: the maturing of stem cells, and the spreading of breast cancer cells on an extracellular matrix.

We learned from these experiments that not only the GAG chains but also the core proteins contribute to proteoglycan function, says Critcher. Notably, we also found that proteoglycans role in cancer cell spreading depends heavily on whether they are anchored to the cell membrane or free-floating.

The team also incorporated a method called proximity tagging to help them identify proteoglycans interaction partners. Huang and colleagues are now using this, and their modular construction technique, to study the interactions of syndecans and other proteoglycans in different contextsand with different GAG arrangementsand otherwise to explore their structures and functions.

Chemical editing of proteoglycan architecture was co-authored by Timothy OLeary, Meg Critcher, Tesia Stephenson, Xueyi Yang, Abdullah Hassan, Noah Bartfield, Richard Hawkins, and Mia Huang.

Funding for the research was provided by the National Institutes of Health (R00HD090292, R35GM142462).

About Scripps Research

Scripps Research is an independent, nonprofit biomedical institute ranked the most influential in the world for its impact on innovation by Nature Index. We are advancing human health through profound discoveries that address pressing medical concerns around the globe. Our drug discovery and development division, Calibr, works hand-in-hand with scientists across disciplines to bring new medicines to patients as quickly and efficiently as possible, while teams at Scripps Research Translational Institute harness genomics, digital medicine and cutting-edge informatics to understand individual health and render more effective healthcare. Scripps Research also trains the next generation of leading scientists at our Skaggs Graduate School, consistently named among the top 10 US programs for chemistry and biological sciences. Learn more atwww.scripps.edu.

Nature Chemical Biology

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Sugared proteins called proteoglycans start to give up their secrets - EurekAlert

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Mucosal barrier injury (MBI) in the gastrointestinal tract remains a major clinical obstacle in the effective treatment of hematological malignancies, driving local and systemic complications that negatively impact treatment outcomes. Here, we provide the first evidence of hyper-activation of the IL-1/CXCL1/neutrophil axis as a major driver of MBI (induced by melphalan), which supports evaluating the IL-1RA anakinra, both preclinically and clinically. Our data reinforce that strengthening the mucosal barrier with anakinra is safe and effective in controlling MBI which in turn, stabilises the host microbiota and minimises febrile events. Together, these findings represent a significant advance in prompting new therapeutic initiatives that prioritise maintenance of the gut microenvironment.

The IL-1/CXCL1/neutrophil axis is documented to drive intestinal mucosal inflammation, activated by ligation of intestinal pattern recognition receptors, including toll-like receptors (TLRs)31. In the context of MBI, TLR4 activation is known to drive intestinal toxicity32, 33, however targeting TLR4 directly is challenging due to emerging regulation of tumour response34,35,36,37. As such, we selected anakinra as our intervention to inhibit inflammatory mechanisms downstream of TLR4. While anakinra was able to minimise the intensity and duration of MBI, it did not completely prevent it with comparable citrulline dynamics across animal groups in the first 48h after melphalan treatment. This reflects the core pathobiological understanding of MBI which is initiated by direct cytotoxic events which activate a cascade of inflammatory signalling that serve to exacerbate mucosal injury and the subsequent breakdown of the mucosal barrier33. By preventing this self-perpetuating circle of injury with anakinra, we were able to effectively minimise the duration of MBI and thus have a profound impact on the clinical symptomology associated with MBI including weight loss and anorexia. These findings firstly highlight the cluster of (pre-)clinical symptoms related to MBI (malnutrition, anorexia, diarrhea)38 and suggest that the mucoprotective properties of anakinra will provide broader benefits to the host, mitigating the need for intensive supportive care interventions (e.g. parenteral nutrition).

In line with our hypothesised approach, minimising the duration of MBI reduced secondary events including enteric pathobiont expansion and fever. This again reiterates that changes in the host microbiome and associated complications can be controlled by strengthening the mucosal barrier39. It can be postulated that by minimising the intensity of mucosal injury, the hostility of the microbial environment is reduced ensuring populations of commensal microbes to be maintained. This is supported by our results with the abundance of Faecalibaculum maintained throughout the time course of MBI. Faecalibaculum is a potent butyrate-producing bacterial genus documented to control pathogen expansion by acidification of the luminal environment. Administration of Faecalibacteria prausnitzii has been shown to reduce infection load in a model of antibiotic-induced Clostridioides difficile infection, whilst also showing mucoprotective benefits in models of MBI40, 41. Furthermore, it is documented to cross feed other commensal microbes increasing colonization resistance. Together, these underscore the luminal benefits of strengthening the mucosal barrier and suggest that maintenance of commensal microbes is central to minimizing translocation events and subsequent BSI.

In our clinical Phase IIA study with 3+3 design, we have shown that treatment with anakinra, up until a dose of 300mg, appears to be safe, feasible, and tolerated well. Of course, the sample size of this study was relatively small. However, anakinra was previously evaluated for its efficacy in the treatment of acute and chronic GvHD in patients allogeneic HSCT. In these studies, patients were treated for a similar time period (with higher doses of anakinra). No differences were seen between the anakinra and placebo group regarding (S)AEs, including infections and time to neutrophil recovery. There were no significant changes in our exploratory analyses, however, it was of note to see marked increase in IL-10 in patients that received 300mg anakinra. This may reflect anakinras capacity to promote anti-inflammatory signaling as observed in COVID-19 related respiratory events42. However, with our sample size it is not possible to make any conclusions on this mechanism. Our conclusion is that the recommended dose (RP2D) for anakinra is 300mg QD, which will be investigated in Phase IIB trial (AFFECT-2 study: Anakinra: Efficacy in the Management of Fever During Neutropenia and Mucositis in ASCT; clinicaltrials.gov identifier NCT04099901)43.

While encouraging, our data must be viewed in light of some limitations. Most importantly, our animal model purposely did not include any antimicrobials as we aimed to dissect the true contribution of MBI in pathogen expansion and subsequent febrility. While it is unclear if melphalan has a direct cytotoxic effect on the microbiota, it is likely that MBI drives dysbiosis with antibiotics serving to exacerbate these changes, with previous data demonstrating no direct impact of specific chemotherapeutic agents on microbial viability44. As such, assuming dysbiosis is secondary to mucosal injury as recently demonstrated45, we anticipate that anakinra will still have an appreciable impact on the severity of dysbiosis and may even prompt more protocolised/limited antibiotic use. Similarly, while we used body temperature as an indicator of BSI, we did not culture peripheral blood or mesenteric lymph nodes as was performed in our animal model development. The ability of anakinra to prevent BSI and thus minimise antibiotic use will be best evaluated in AFFECT-2 where routine blood culture is performed. It is also important to consider that we detected episodes of bacteremia in our participants that were likely caused by skin colonizing organisms; a mechanism anakinra will not influence. While these are expected in HSCT recipients, the majority of infectious cases originate from the gut, and we therefore anticipate anakinras capacity to strengthen the mucosal barrier will be clinically impactful in our next study. It must also be acknowledged that limited mechanistic investigations were conducted to identify the way in which anakinra provided mucoprotection. It is well documented that MBI is highly multifactorial, involving mucosal, microbial and metabolic dysfunction33, 46; each of which is mediated through aberrant cytokine production. It is therefore unlikely that anakinra will affect distinct pathways, instead dampening multiple mechanisms. In translating this evidence to the clinic, the impact of anakinra on symptom control is of greater significance than mechanistic insight.

In conclusion, we have demonstrated that not only is anakinra safe in HSCT recipients treated with HDM, but may also be an effective strategy to prevent acute MBI. Our data are critical in supporting new antibiotic stewardship efforts directed at mitigating the emerging consequences of antibiotic use. We suggest that minimizing the severity and duration of MBI is an important aspect of infection control that may optimize the efficacy of anti-cancer treatment, decreasing its impact on antibiotic resistance and the long-term complications associated with microbial disruption.

This study is reported using the ARRIVE guidelines for the accurate and reproducible reporting of animal research.

All animal studies were approved by the Dutch Centrale Commissie Dierproeven (CCD) and the Institutional Animal Care and Use Committee of the University Medical Centre Groningen, University of Groningen (RUG), under the license number 171325-01(-002). The procedures were carried out in accordance with the Dutch Experiments on Animals (Wet op de Dierproeven) and the EU Directive 2010/63/EU. All animals were individually housed in conventional, open cages at the Centrale Dienst Proefdieren (CDP; Central Animal Facility) at the University Medical Centre Groningen. Rats (single housed) were housed under 12h light/dark cycles with ad libitum access to autoclaved AIN93G rodent chow and sterile water. All rats acclimatised for 10days and randomised to their treatment groups via a random number sequence generated in Excel. Small adjustments were made to ensure comparable body weight at the time of treatment and cages were equally distributed across racks to minimise confounding factors. HRW was responsible for animal allocation and assessments while RH/ARDSF performed treatments. Softened chow and subcutaneous saline were provided to rats to reduce suffering/distress and were humanely euthanised if a clinical toxicity score>/=12 was observed. This score was calculated based on weight loss, diarrhea, reluctance to move, coat condition and food intake; each of which were assessed 03. At completion of the study, rats were anaesthetised with 5% isoflurane in an induction chamber, followed by cardiac puncture and cervical dislocation (isoflurane provided by a facemask).

We have previously reported on the development and validation of our HDM model of MBI, which exhibits both clinical and molecular consistency with patients undergoing HDM treatment21. During model development, plasma (isolated from whole blood) was collected and stored for cytokine analysis to inform the selection of our intervention. Repeated whole blood samples (75l) were collected from the tail vein into EDTA-treated haematocrit capillary tubes on day 0, 4, 7 and 10.

Cytokines (IFN-, IL-1, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO and TNF-) using the Meso Scale Discovery V-Plex Proinflammatory Panel Rat 2 following manufacturers guidelines. On the day of analysis, all reagents were brought to room temperature, samples were centrifuged to remove any particulate matter and diluted 1:4. Data analysis was performed using the Meso Scale Discovery Workbench.

Male albino Wistar rats (150180g) were randomized (Excel number generator) to one of four experimental groups (N=16/group): (1) controls (phosphate buffered saline (PBS)+0.9% NaCl), (2) anakinra+0.9% NaCl, (3) PBS+melphalan, and (4) anakinra+melphalan. Melphalan was administered as a single, intravenous dose on day 0 (5mg/kg, 10mg/ml) via the penile vein under 3% isoflurane anaesthetic. Anakinra was administered subcutaneously (100mg/kg, 150mg/ml) twice daily from day 1 to+4 (8 am and 5pm). N=4 rats per group were terminated at the exploratory time points (day 4, and 7) and N=8 on day 10 (recovery phase) by isoflurane inhalation (3%) and cervical dislocation. The primary endpoint for the intervention study was plasma citrulline, a validated biomarker of MBI19, 47, which was used for all power calculations (N=8 required, alpha=0.05, beta=0.8).

Clinical manifestations of MBI were assessed using validated parameters of body weight, food intake and water intake, as well as routine welfare indicators (movement, posture, coat condition). Rats were weighed daily, and water/food intake monitored by manual weighing of chow and water bottles.

Plasma citrulline is an indicator of intestinal enterocyte mass48, and a validated biomarker of intestinal MBI. Repeated blood samples (75l) were collected from the tail vein into EDTA-treated haematocrit capillary tubes on day 0, 2, 4, 6, 7, 8 and 10. Citrulline was determined in 30l of plasma (isolated from whole blood via centrifugation at 4000g for 10min) using automated ion exchange column chromatography as previously described49.

Whole blood samples (200l) were collected from the tail vein into MiniCollect EDTA tubes on day 0, 4, 7 and 10 for differential morphological analysis which included: white blood cell count (WBC, 109/L), red blood cell count (RBC, 109/L), haemoglobin (HGB, mmol/L), haematocrit (HCT, L/L), mean corpuscular volume (MCV, fL), mean corpuscular haemoglobin (MCH, amol), mean corpuscular hemoglobin concentration (MCHC, mmol/L), platelet count (PLT, 109/L), red blood cell distribution width (RDW-SD/-CV, fL/%), mean platelet volume (fL), mean platelet volume (MPV, fL), platelet large cell ratio (P-LCR, %), procalcitonin (PCT, %), nucleated red blood cell (NRBC, 109/L and %), neutrophils (109/L and %), lymphocytes (109/L and %), monocytes (109/L and %), eosinophils (109/L and %), basophils (109/L and %) and immunoglobulins (IG, 109/L and %). For the purpose of the current study only neutrophils, lymphocytes and monocytes were evaluated.

Core body temperature was used as an indicator of fever. Body temperature was assessed daily using the Plexx B.V. DAS-7007R handheld reader and IPT programmable transponders. Transponders were inserted subcutaneously under mild 2% isoflurane anaesthesia on day 4. Average values from day 4 to 1 were considered as baseline body temperature.

The microbiota composition was assessed using 16S rRNA sequencing in N=8 rats/group. Repeated faecal samples were collected on day 0, 4, 7 and 10 and stored at 80C until analysis. Sample preparation (including DNA extraction, PCR amplification, library preparation), quality control, sequencing and analyses were all performed by Novogene (please see supplementary methods for full description).

All data (excluding 16S data) were analysed in GraphPad Prism (v8.0. Repeated measures across multiple groups were assessed by mixed-effect models with appropriate post-hoc analyses. Terminal data analyses were assessed by one-way ANOVA. Statistical analyses are outlined in figure legends and P<0.05 was considered significant.

This Phase IIA trial (AFFECT-1: NCT03233776, 17/6/2017) aimed to i) assess the safety of anakinra in autologous HSCT recipients undergoing conditioning with HDM, and ii) determine the maximum tolerated dose of anakina (100, 200 or 300mg).

This study was approved by the ethical committee Nijmegen-Arnhem (NL59679.091.16; EudraCT 2016-004,419-11) and performed in accordance with (a) theDeclaration of Helsinki (1964, amended October 2013), (b) Medical Research Involving Human Subjects Act and c) Good Clinical Practice guidelines.We enrolled patients from Radboud University Medical Centre who were at least 18years of age and were scheduled to undergo an autologous HSCT after receiving conditioning with HDM (200mg/m2) for multiple myeloma. All participants provided informed consent. Important exclusion criteria were active infections, a history of tuberculosis or positive Quantiferon, glomular filtration rate<40ml/min, and colonization with highly resistant micro-organisms or with gram-negative bacteria resistant to ciprofloxacin.

Patients were involved in the design of the AFFECT trials, through involvement of Hematon, a patient organization for patients with hemato-oncological diseases in the Netherlands. The project plan, including trial materials, have been presented to patient experts from Hematon. They have given their advice on the project, and provided input on the design of the study as well as on patient information. Patients will also be involved in the dissemination of the results of the AFFECT trials. Information on both the design as well as the outcome of the AFFECT trials is and/or will be available on websites specifically aimed at patients, such as the Dutch website kanker.nl.

Conforming with routine clinical practice and care, study participants were admitted at day 3, treated with melphalan 200mg/m2 at day 2, and received their autologous HSCT at day 0. They were treated with IL-1RA anakinra (Kineret, SOBI) intravenously once daily from day 2 up until day+12.

A traditional 3+3 design was used (Fig. S1), in which the first cohort of patients was treated with 100mg, the next cohort with 200mg and the third cohort with 300mg of anakinra. In this study design, the cohort is expanded when dose limiting toxicities (DLTs) occur. The primary study endpoint was safety, using the common toxicity criteria (CTCAE) version 4.050, as well as the maximum tolerated dose of anakinra (MTD; 100, 200 or 300mg). DLTs were defined as the occurrence of (1) an infection due to an opportunistic pathogen (including Pneumocystis jirovecii pneumonia, mycobacterial infections and invasive mould disease), (2) a suspected unexpected serious adverse reaction (SUSAR), (3) severe non-hematological toxicity grade 34 (meaning toxicity that does not commonly occur in the treatment with HDM and HSCT, or that is more severe than is to be expected with standard treatment) and (4) primary graft failure or prolonged neutropenia (neutrophils have not been>0.5109/l on one single day, assessed on day+21, and counting from day 0).

Secondary endpoints included: incidence of fever during neutropenia (defined as a tympanic temperature38.5C and an absolute neutrophil count (ANC)<0.5109/l, or expected to fall below 0.5109/l in the next 48h), CRP levels, intestinal mucositis as measured by (the AUC of) citrulline, clinical mucositis as determined by daily mouth and gut scores, incidence and type of BSI, short term overall survival (100days and 1year after HSCT), length of hospital stay in days and use of systemic antimicrobial agents, analgesic drugs and total parenteral nutrition (incidence and duration).

Patients received standard antimicrobial prophylaxis including ciprofloxacin and valacyclovir, as well as antifungal prophylaxis (fluconazole) on indication; i.e. established mucosal colonization. Upon occurrence of fever during neutropenia, empirical treatment with ceftazidime was started. The use of therapies to prevent or treat mucositis (i.e. oral cryotherapy) was prohibited. Also, treatment with acetaminophen or non-steroidal anti-inflammatory drugs was not allowed during hospital admission. All other supportive care treatments (i.e. morphine, antiemetics, transfusions, TPN) were allowed.

Laboratory analysis was performed three times a week, which included hematological and chemistry panels and plasma collection for citrulline analysis. Blood cultures were drawn daily from day+4 up until day+12, which was halted upon occurrence of fever. Outside this period, conforming to standard of care, blood cultures were drawn twice weekly and in occurrence of fever. Conforming standard of care, surveillance cultures of mucosal barriers were obtained twice weekly.

Plasma was longitudinally collected from participants throughout the study period for the evaluation of cytokines using the Meso Scale Discovery Customised U-Plex 9-analyte panel following manufacturers guidelines (IL-1/, IL-1RA, CXCL1, TNF, IL-10, IL-17, IL-6, GM-CSF). 16S sequencing was performed by Novogene (as per preclinical analysis methodology).

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WIN: A beauty box of dreams valued at R3000

Winters whispers are quickly reaching a crescendo, and that means giving your skin and glam routine a big, warm hug. Finding what products work for you can be a painstaking and expensive task. So, weve put together a fabulous Beauty Box full of goodies just for you.

With the help of expert local beauty Editor, Jade Smith, the Beauty Box has been curated with nothing short of the best products. It contains nine items that, together, are valued at R3 000.

Jade Smith is the beauty brain behind some of South Africas most adored magazines, including Woman&Home, and has over 20 years of experience in the industry. She started her career as a make-up artist and has worked on many international campaigns in London and Europe, including work for iconic brands like Tom Ford and Dove. Every product is personally tried and tested and selected by Jade and only the best makes it into the box.

In sharing a little warmth this winter, Cape {town} Etc is giving away three Beauty Boxes to three lucky winners. Get ready to glow all season long.

1. Afari Overnight Regenerating Cream 50ml

A luxurious overnight skin-repairing cream loaded with potent ingredients to help skin look renewed by morning. It helps to boost natural collagen production and speed up cell turnover for bouncier, smoother skin.

This brand is proudly South African, free from nasties, and cruelty-free.

Explore more onwww.afari.co.zaor@afariskincare

2. SKOON Happy Flora Face Moisturiser 15ml

Join the good bacteria movement and re-balance your skins microbiome. Made with Swiss yoghurt and Quora Noni an active ingredient derived from plant stem cells that help to control bacteria.

This brand is proudly South African, free from nasties, and cruelty-free.

Explore more onwww.skoonskin.comor@skoonskin

3. Gatineau Defi Lift 3D Firming Neck & Dcollet Gel 15ml

A gel formula formulated to help tighten skin and visibly firm the delicate neck and dcollet area thanks to Plant Proteins, encapsulated Hyaluronic Acid and Fixlift technology.

Tip: Use gentle, upward strokes all the way up to the jawline using your hands or your favourite stone roller.

Explore more onwww.gatineau.comor@gatineau_sa

4. Rimmel WonderLuxe Volume Mascara in Black

This mascara promises to give lashes full-bodied volume without looking clumpy or weighing lashes down. It also includes Argan, Maracuja, Marula and Calmellia oils to nourish and protect lashes.

Ophthalmologist tested it, which means its safe for contact lens wearers too.

Explore more onwww.rimmellondon.com/en-zaor@rimmellondonsa

5. Berdoues Azur Riviera 10ml

It can be tricky to find your signature scent, which is why its best to test it first. This one is fresh and clean, perfect for both you and your partner, with marine and aquatic notes softened with Orange Blossom and Jasmine at the heart.

Explore more onwww.berdoues.comor@berdouesgrandscrussa

6. BIODERMA Photoderm AKN Mat Sunscreen Cream SPF 30

A mattifying sun protection fluid thats lighter than air and ideal for all skin types. Furthermore, it helps to prevent the appearance of blemishes while protecting against cellular damage, shielding against UVA and UVB, and free radicals.

Explore more onwww.bioderma.co.zaor@biodermasouthafrica

7. Litchi & Titch Mini Aromatherapy Serum

Made with essential oils and botanical extracts of the highest quality, this blend is made with calmness and serenity in mind. Neroli, Grapefruit and Chamomile are heroed, and the formula is suitable for all skin types.

Tip: Apply 5 to 7 drops of the serum and press onto the skin after misting or dampening skin slightly, then cup your hands over your nose and breathe in to set a calming mood.

This brand is proudly South African, free from nasties, and cruelty-free.

Explore more onwww.litchiandtitchnaturals.comor@litchiandtitchnaturals

8. NUXE rve de miel Face & Body Gel 100ml

An ultra-rich cleansing gel using natural active ingredients such as honey, coconut and sunflower. The formula is gentle, yet effective enough to be used on your face and body, and is especially suitable for dry and sensitive skin.

Tip: Thanks to the deliciously rich and creamy texture, it works wonderfully for shaving.

Explore more onwww.nuxe.comor@nuxe_sa

9. Skin Republic Wrinkle Smooth Complex Sheet Mask

A biodegradable sheet mask packed with Adenosine, Green Tea and Plant Stem Cells was chosen for their skin-firming and texture-smoothing powers.

Explore more onwww.theskinrepublic.co.zaor@skinrepublic

To enter, fill in your details and answer the question below:

*Winners will be announced Monday 15 May 2022.

*Hint: All entrants can expect some exciting news on Monday 15 May 2022.

Question: Which item in the Beauty Box are you most excited to try?

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WIN: A beauty box of dreams valued at R3000 - CapeTown ETC

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Worlds 1st Focused Ultrasound Cancer Immunotherapy Center LaunchedUVA Health and the Charlottesville-based Focused Ultrasound Center today announced the launch of theFocused Ultrasound Cancer Immunotherapy Center, the worlds first center dedicated specifically to advancing a focused ultrasound and cancer immunotherapy treatment approach that could revolutionize 21st-century cancer care.

A Study by the Gwangju Institute of Science and Technology Investigates Mercury Contamination in Freshwater Lakes in KoreaDuring the 1950s and 1960s, Minamata Bay in Japan was the site of widespread mercury poisoning caused by the consumption of fish containing methylmercurya toxic form of mercury that is synthesized when bacteria react with mercury released in water.

Researchers identify possible new target to treat newborns suffering from lack of oxygen or blood flow in the brainThe condition, known as hypoxic-ischemic encephalopathy (HIE), can result in severe brain damage, which is why researchers at theCase Western Reserve University School of Medicineand UH Rainbow Babies & Childrens Hospital (UH Rainbow) are studying the condition to evaluate how HIE is treated and develop new, more effective options.

Should You Give Your Child Opioids for Post-Operative Pain Management?Routine head and neck procedures, such as removal of tonsils and adenoids and the placement of ear tubes, may cause moderate to severe pain in pediatric patients.

Two birds with one stone: a refined bioinformatic analysis can estimate gene copy-number variations from epigenetic dataA team led by Dr. Manel Esteller, Director of the Josep Carreras Leukaemia Research Institute, has improved the computational identification of potentially druggable gene amplifications in tumors, from epigenetic data.

Some Shunts Used After Epilepsy Surgery May Risk Chronic HeadachesSurgeons who observe persistent fluid buildup after disconnecting epileptic and healthy brain areas should think twice before installing low-pressure nonprogrammable drainage shunts, according to a study coauthored by Rutgers pediatric and epilepsy neurosurgeonYasunori Nagahamathat found chronic headaches could result from these procedures.

Re-defining the selection of surgical procedure in sufferers with tuberous sclerosis complicatedBy illustrating a number of instances of tuberous sclerosis in sufferers whove undergone surgical resection with seizure-free outcomes, researchers have recognized components that decide choice of sufferers for profitable surgical procedure.

Scientists study links between obesity, age and body chemistryA team of Clemson University scientists is making inroads in understanding the relationship between certain enzymes that are normally produced in the body and their role in regulating obesity and controlling liver diseases.

Clemson scientists discover new tools to fight potentially deadly protozoa that has pregnant women avoiding cat litter boxesNow, a group of researchers from Clemson University have discovered a promising therapy for those who suffer from toxoplasmosis, a disease caused by the microscopic protozoa Toxoplasma gondii.

Rising income inequality linked to Americans declining healthRising levels of income inequality in the United States may be one reason that the health of Americans has been declining in recent decades, new research suggests.

New research to understand how the brain handles optical illusions and makes predictionsNew research projects are underway at the Allen Institute to address these questions through OpenScope, the shared neuroscience observatory that allows scientists around the world to propose and direct experiments conducted on one of the Institutes high-throughput experimental platforms.

Robotic therapy: A new effective treatment for chronic stroke rehabilitationA study led by Dr. Takashi Takebayashi and published in the journal Stroke suggests continuing therapy for chronic stroke patients is still beneficial while suggesting a radical alternative.

Children with history of maltreatment could undergo an early maturation of the immune systemThe acute psychosocial stress states stimulate the secretion of an antibody type protein which is decisive in the first immune defence against infection, but only after puberty.

Toxoplasmosis: propagation of parasite in host cell stoppedA new method blocks the protein regulation of the parasite Toxoplasma gondii and causes it to die off inside the host cell.

Research shows the role empathy may play in musicCan people who understand the emotions of others better interpret emotions conveyed through music? A new study by an international team of researchers suggests the abilities are linked.

Effects of stress on adolescent brains triple networkA new studyinBiological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier, has used functional magnetic resonance imaging (fMRI) to examine the effects of acute stress and polyvicitimization, or repeated traumas, on three brain networks in adolescents.

Reform to Mental Health Act must prompt change in support for familiesFamily members of people with severe mental health challenges need greater support to navigate the UKs care system following changes announced in yesterdays Queens Speech, say the authors of a new study published in theBritish Journal of Social Work.

New knowledge about airborne virus particles could help hospitalsMeasurements taken by researchers at Lund University in Sweden of airborne virus in hospitals provide new knowledge about how best to adapt healthcare to reduce the risk of spread of infection.

Guidance developed for rare dancing eyes syndromeExperts from Evelina London Childrens Hospital developed the guidance in collaboration with a worldwide panel of experts and families of children with the condition.

Genetic study identifies migraine causes and promising therapeutic targetsQUT genetic researchers have found blood proteins that cause migraine and have a shared link with Alzheimers disease that could potentially be prevented by repurposing existing therapeutics.

How do genomes evolve between species? The key role of 3D structure in male germ cellsA study led by scientists at the UAB and University of Kent uncovers how the genome three-dimensional structure of male germ cells determines how genomes evolve over time.

Novel Supramolecular CRISPRCas9 Carrier Enables More Efficient Genome EditingRecently, a research team from Kumamoto University, Japan, have constructed a highly flexible CRISPR-Cas9 carrier using aminated polyrotaxane (PRX) that can not only bind with the unusual structure of Cas9 and carry it into cells, but can also protect it from intracellular degradation by endosomes.

Obesity, diabetes and high blood pressure increase mortality from COVID-19 especially among young and middle-aged peopleObesity, impaired blood glucose metabolism, and high blood pressure increase the risk of dying from COVID-19 in young and middle-aged people to a level mostly observed in people of advanced age.

Are most ORR electrocatalysts promising nanocatalytic medicines for tumor therapy?The current searches for medical catalysts mainly rely on trial-and-error protocols, due to the lack of theoretical guidance.

The combination makes the difference: New therapeutic approach against breast cancerResearchers at the University of Basel have now discovered an approach that involves a toxic combination with a second target gene in order to kill the abnormal cells.

Glatiramer acetate compatible with breastfeedingA study conducted by the neurology department of Ruhr-Universitt Bochum (RUB) at St. Josef Hospital on the drug glatiramer acetate can relieve mothers of this concern during the breastfeeding period.

A*STAR, NHCS, NUS And Novo Nordisk To Collaborate On Cardiovascular Disease ResearchThe Agency for Science, Technology and Researchs (A*STAR) Genome Institute of Singapore (GIS) and Bioinformatics Institute (BII), as well as the National Heart Centre Singapore (NHCS), National University of Singapore (NUS), and pharmaceutical company Novo Nordisk have signed an agreement to study the mechanisms underlying cardiovascular disease progressionespecially the condition called heart failure with preserved ejection fraction (HFpEF).

Taking ownership of your healthA study published this month inAge and Ageing by The Japan Collaborate Cohort (JACC) Study group at Osaka University assessed the impact of modifying lifestyle behaviors on life expectancy from middle age onwards.

Experimental evolution illustrates gene bypass process for mitosisResearchers from Nagoya University demonstrated gene bypass events for mitosis using evolutionary repair experiments.

Temporomandibular Disorder-Induced Pain Likely to Worsen in Late Menopause TransitionNew study evaluates the influence of menopause symptoms on the intensity of temporomandibular disorder-induced pain throughout the full menopause transition.

Breathtaking solution for a breathless problemA drop in oxygen levels, even when temporary, can be critical to brain cells. This explains why the brain is equipped with oxygen sensors. Researchers from Japan and the United States report finding a new oxygen sensor in the mouse brain.

How calming our spinal cords could provide relief from muscle spasmsAn Edith Cowan University (ECU) studyinvestigating motoneurons in the spine has revealed two methods can make our spinal cords less excitable and could potentially be usedto treat muscle spasms.

Analysis Finds Government Websites Downplay PFAS Health RisksState and federal public health agencies often understate the scientific evidence surrounding the toxicity of per- and polyfluoroalkyl substances (PFAS) in their public communications, according toan analysispublished today in the journalEnvironmental Health.

Multiple diagnoses are the norm with mental illness; new genetic study explains whyThe study, published this weekin the journalNature Genetics, found that while there is no gene or set of genes underlying risk for all of them, subsets of disordersincluding bipolar disorder and schizophrenia; anorexia nervosa and obsessive-compulsive disorder; and major depression and anxietydo share a common genetic architecture.

Drinkers sex plus brewing method may be key to coffees link to raised cholesterolThe sex of the drinker as well as the brewing method may be key to coffees link with raised cholesterol, a known risk factor for heart disease, suggests research published in the open access journalOpen Heart.

Artificial cell membrane channels composed of DNA can be opened and locked with a keyIn new research, Arizona State University professorHao Yan, along with ASU colleagues and international collaborators from University College London describe the design and construction of artificial membrane channels, engineered using short segments of DNA.

Single cell RNA sequencing uncovers new mechanisms of heart diseaseResearchers at the Hubrecht Institute have now successfully applied a new revolutionary technology (scRNA-seq) to uncover underlying disease mechanisms, including specifically those causing the swelling.

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Other Notable Health Studies & Research From May 11, 2022 - Study Finds

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The new multi-organ chip has the size of a glass microscope slide and allows the culture of up to four human engineered tissues, whose location and number can be tailored to the question being asked. These tissues are connected by vascular flow, but the presence of a selectively permeable endothelial barrier maintains their tissue-specific niche. Credit: Kacey Ronaldson-Bouchard/Columbia Engineering

Major advance from Columbia Engineering team demonstrates the first multi-organ chip made of engineered human tissues linked by vascular flow for improved modeling of systemic diseases like cancer.

Engineered tissues have become an essential component for modeling diseases and testing the efficacy and safety of drugs in a human context. A key hurdle for researchers has been figuring how to model body functions and systemic diseases with multiple engineered tissues that can physiologically communicate just like they do in the body. However, it is essential to provide each engineered tissue with its own environment so that the specific tissue phenotypes can be maintained for weeks to months, as required for biological and biomedical studies. Making the challenge even more complex is the necessity of linking the tissue modules together to facilitate their physiological communication, which is required for modeling conditions that involve more than one organ system, without sacrificing the individual engineered tissue environments.

Up to now, no one has been able to meet both conditions. Today, a team of researchers from Columbia Engineering and Columbia University Irving Medical Center reports that they have developed a model of human physiology in the form of a multi-organ chip consisting of engineered human heart, bone, liver, and skin that are linked by vascular flow with circulating immune cells, to allow recapitulation of interdependent organ functions. The researchers have essentially created a plug-and-play multi-organ chip, which is the size of a microscope slide, that can be customized to the patient. Because disease progression and responses to treatment vary greatly from one person to another, such a chip will eventually enable personalized optimization of therapy for each patient. The study is the cover story of the April 2022 issue of the journal Nature Biomedical Engineering.

In our study, we cultured liver, heart, bone, and skin, connected by vascular flow for four weeks. These tissues can be generated from a single human induced pluripotent stem cell, generating a patient-specific chip, a great model for individualized studies of human disease and drug testing. Credit: Keith Yeager/Columbia Engineering

This is a huge achievement for usweve spent ten years running hundreds of experiments, exploring innumerable great ideas, and building many prototypes, and now at last weve developed this platform that successfully captures the biology of organ interactions in the body, said the project leader Gordana Vunjak-Novakovic, University Professor and the Mikati Foundation Professor of Biomedical Engineering, Medical Sciences, and Dental Medicine.

Taking inspiration from how the human body works, the team has built a human tissue-chip system in which they linked matured heart, liver, bone, and skin tissue modules by recirculating vascular flow, allowing for interdependent organs to communicate just as they do in the human body. The researchers chose these tissues because they have distinctly different embryonic origins, structural and functional properties, and are adversely affected by cancer treatment drugs, presenting a rigorous test of the proposed approach.

The tissues cultured in the multi-organ chip (skin, heart, bone, liver, and endothelial barrier from left to right) maintained their tissue-specific structure and function after being linked by vascular flow. Credit: Kacey Ronaldson-Bouchard/Columbia Engineering

Providing communication between tissues while preserving their individual phenotypes has been a major challenge, said Kacey Ronaldson-Bouchard, the studys lead author and an associate research scientist in Vunjak-Novakovics Laboratory for Stem Cells and Tissue Engineering. Because we focus on using patient-derived tissue models we must individually mature each tissue so that it functions in a way that mimics responses you would see in the patient, and we dont want to sacrifice this advanced functionality when connecting multiple tissues. In the body, each organ maintains its own environment, while interacting with other organs by vascular flow carrying circulating cells and bioactive factors. So we chose to connect the tissues by vascular circulation, while preserving each individual tissue niche that is necessary to maintain its biological fidelity, mimicking the way that our organs are connected within the body.

The group created tissue modules, each within its optimized environment and separated them from the common vascular flow by a selectively permeable endothelial barrier. The individual tissue environments were able to communicate across the endothelial barriers and via vascular circulation. The researchers also introduced into the vascular circulation the monocytes giving rise to macrophages, because of their important roles in directing tissue responses to injury, disease, and therapeutic outcomes.

All tissues were derived from the same line of human induced pluripotent stem cells (iPSC), obtained from a small sample of blood, in order to demonstrate the ability for individualized, patient-specific studies. And, to prove the model can be used for long-term studies, the team maintained the tissues, which had already been grown and matured for four to six weeks, for an additional four weeks, after they were linked by vascular perfusion.

The researchers also wanted to demonstrate how the model could be used for studies of an important systemic condition in a human context and chose to examine the adverse effects of anticancer drugs. They investigated the effects of doxorubicin a broadly used anticancer drug on heart, liver, bone, skin, and vasculature. They showed that the measured effects recapitulated those reported from clinical studies of cancer therapy using the same drug.

The team developed in parallel a novel computational model of the multi-organ chip for mathematical simulations of drugs absorption, distribution, metabolism, and secretion. This model correctly predicted doxorubicins metabolism into doxorubicinol and its diffusion into the chip. The combination of the multi-organ chip with computational methodology in future studies of pharmacokinetics and pharmacodynamics of other drugs provides an improved basis for preclinical to clinical extrapolation, with improvements in the drug development pipeline.

While doing that, we were also able to identify some early molecular markers of cardiotoxicity, the main side-effect that limits the broad use of the drug. Most notably, the multi-organ chip predicted precisely the cardiotoxicity and cardiomyopathy that often require clinicians to decrease therapeutic dosages of doxorubicin or even to stop the therapy, said Vunjak-Novakovic.

The development of the multi-organ chip began from a platform with the heart, liver, and vasculature, nicknamed the HeLiVa platform. As is always the case with Vunjak-Novakovics biomedical research, collaborations were critical for completing the work. These include the collective talent of her laboratory, Andrea Califano and his systems biology team (Columbia University), Christopher S. Chen (Boston University) and Karen K. Hirschi (University of Virginia) with their expertise in vascular biology and engineering, Angela M. Christiano and her skin research team (Columbia University), Rajesh K. Soni of the Proteomics Core at Columbia University, and the computational modeling support of the team at CFD Research Corporation.

The research team is currently using variations of this chip to study, all in individualized patient-specific contexts: breast cancer metastasis; prostate cancer metastasis; leukemia; effects of radiation on human tissues; the effects of SARS-CoV-2 on heart, lung, and vasculature; the effects of ischemia on the heart and brain; and the safety and effectiveness of drugs. The group is also developing a user-friendly standardized chip for both academic and clinical laboratories, to help utilize its full potential for advancing biological and medical studies.

Vunjak-Novakovic added, After ten years of research on organs-on-chips, we still find it amazing that we can model a patients physiology by connecting millimeter sized tissues the beating heart muscle, the metabolizing liver, and the functioning skin and bone that are grown from the patients cells. We are excited about the potential of this approach. Its uniquely designed for studies of systemic conditions associated with injury or disease, and will enable us to maintain the biological properties of engineered human tissues along with their communication. One patient at a time, from inflammation to cancer!

Reference: A multi-organ chip with matured tissue niches linked by vascular flow by Kacey Ronaldson-Bouchard, Diogo Teles, Keith Yeager, Daniel Naveed Tavakol, Yimu Zhao, Alan Chramiec, Somnath Tagore, Max Summers, Sophia Stylianos, Manuel Tamargo, Busub Marcus Lee, Susan P. Halligan, Erbil Hasan Abaci, Zongyou Guo, Joanna Jackw, Alberto Pappalardo, Jerry Shih, Rajesh K. Soni, Shivam Sonar, Carrie German, Angela M. Christiano, Andrea Califano, Karen K. Hirschi, Christopher S. Chen, Andrzej Przekwas and Gordana Vunjak-Novakovic, 27 April 2022, Nature Biomedical Engineering.DOI: 10.1038/s41551-022-00882-6

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Plug-and-Play Human Organ-on-a-Chip Can Be Customized to the Patient - SciTechDaily

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