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Axolotls can regenerate their brains – Big Think

By daniellenierenberg

Theaxolotl(Ambystoma mexicanum) is an aquatic salamander renowned for its ability toregenerate its spinal cord, heart and limbs. These amphibians alsoreadily make new neuronsthroughout their lives. In 1964, researchers observed that adult axolotls couldregenerate parts of their brains, even if a large section was completely removed. But one study found that axolotlbrain regenerationhas a limited ability to rebuild original tissue structure.

So how perfectly can axolotls regenerate their brains after injury?

As aresearcher studying regeneration at the cellular level, I and my colleagues in theTreutlein Labat ETH Zurich and theTanaka Labat the Institute of Molecular Pathology in Vienna wondered whether axolotls are able to regenerate all the different cell types in their brain, including the connections linking one brain region to another. In ourrecently published study, we created an atlas of the cells that make up a part of the axolotl brain, shedding light on both the way it regenerates and brain evolution across species.

Differentcell typeshave different functions. They are able to specialize in certain roles because they each express different genes. Understanding what types of cells are in the brain and what they do helps clarify the overall picture of how the brain works. It also allows researchers to make comparisons across evolution and try to find biological trends across species.

One way to understand which cells are expressing which genes is by using a technique calledsingle-cell RNA sequencing (scRNA-seq). This tool allows researchers to count the number of active genes within each cell of a particular sample. This provides a snapshot of the activities each cell was doing when it was collected.

This tool has been instrumental in understanding the types of cells that exist in the brains of animals. Scientists have used scRNA-seq infish,reptiles,miceand evenhumans. But one major piece of the brain evolution puzzle has been missing: amphibians.

Our team decided to focus on thetelencephalonof the axolotl. In humans, the telencephalon is the largest division of the brain and contains a region called theneocortex, which plays a key role in animal behavior and cognition. Throughout recent evolution, the neocortex hasmassively grown in sizecompared with other brain regions. Similarly, the types of cells that make up the telencephalon overall havehighly diversifiedand grown in complexity over time, making this region an intriguing area to study.

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We used scRNA-seq to identify the different types of cells that make up the axolotl telencephalon, including different types ofneuronsandprogenitor cells, or cells that can divide into more of themselves or turn into other cell types. We identified what genes are active whenprogenitor cells become neurons, and found that many pass through an intermediate cell type called neuroblasts previously unknown to exist in axolotls before becoming mature neurons.

We then put axolotl regeneration to the test by removing one section of their telencephalon. Using aspecialized method of scRNA-seq, we were able to capture and sequence all the new cells at different stages of regeneration, from one to 12 weeks after injury. Ultimately, we found that all cell types that were removed had been completely restored.

We observed that brain regeneration happens in three main phases. The first phase starts with a rapid increase in the number of progenitor cells, and a small fraction of these cells activate a wound-healing process. In phase two, progenitor cells begin to differentiate into neuroblasts. Finally, in phase three, the neuroblasts differentiate into the same types of neurons that were originally lost.

Astonishingly, we also observed that the severedneuronal connectionsbetween the removed area and other areas of the brain had been reconnected. This rewiring indicates that the regenerated area had also regained its original function.

Adding amphibians to the evolutionary puzzle allows researchers to infer how the brain and its cell types has changed over time, as well as the mechanisms behind regeneration.

When we compared our axolotl data with other species, we found that cells in their telencephalon show strong similarity to the mammalianhippocampus, the region of the brain involved in memory formation, and theolfactory cortex, the region of the brain involved in the sense of smell. We even found some similarities in one axolotl cell type to the neocortex, the area of the brain known for perception, thought and spatial reasoning in humans. These similarities indicate that these areas of the brain may be evolutionarily conserved, or stayed comparable over the course of evolution, and that the neocortex of mammals may have an ancestor cell type in the telencephalon of amphibians.

While our study sheds light on the process of brain regeneration, including which genes are involved and how cells ultimately become neurons, we still dont know whatexternal signalsinitiate this process. Moreover, we dont know if the processes we identified are still accessible to animals that evolved later in time, such as mice or humans.

But were not solving the brain evolution puzzle alone. TheTosches Labat Columbia University explored the diversity of cell types inanother species of salamander, Pleurodeles waltl, while the Fei lab at the Guangdong Academy of Medical Sciences in China and collaborators at life sciences companyBGIexplored how cell types arespatially arranged in the axolotl forebrain.

Identifying all the cell types in the axolotl brain also helps pave the way for innovative research in regenerative medicine. The brains of mice and humans havelargely lost their capacityto repair or regenerate themselves.Medical interventionsfor severe brain injury currently focus on drug and stem cell therapies to boost or promote repair. Examining the genes and cell types that allow axolotls to accomplish nearly perfect regeneration may be the key to improve treatments for severe injuries and unlock regeneration potential in humans.

This article is republished fromThe Conversationunder a Creative Commons license. Read theoriginalarticle.

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IMAC Holdings, Inc. Announces Completion of Third Cohort of its Phase 1 Clinical Study of Umbilical Cord-Derived Mesenchymal Stem Cells for the…

By daniellenierenberg

IMAC Holdings, Inc.

BRENTWOOD, Tenn., Sept. 09, 2022 (GLOBE NEWSWIRE) -- IMAC Holdings, Inc. (Nasdaq: BACK) (IMAC or the Company), today announces it has completed the third cohort of its Phase 1 clinical trial for its investigational compound utilizing umbilical cord-derived allogenic mesenchymal stem cells for the treatment of bradykinesia due to Parkinsons disease.

The third cohort consists of five patients with bradykinesia due to Parkinsons disease receiving an intravenous infusion of a high concentration stem cell treatment. The third and final cohort of the Phase 1 clinical trial was completed on Tuesday, September 6, 2022.

About IMACs Phase 1 Clinical Trial

The Phase 1 clinical trial, consisting of a 15-patient dose escalation safety and tolerability study, is being conducted at three of IMACs clinical centers in Chesterfield, Missouri, Paducah, Kentucky, and Brentwood, Tennessee. The trial is divided into three groups: 1) five patients with bradykinesia due to Parkinsons disease received a low concentration dose, intravenous infusion of stem cells, 2) five received a medium concentration intravenous dose, 3) and five received a high concentration intravenous dose. All groups will be subsequently tracked for 12 months. IMACs medical doctors and physical therapists at the clinical sites have been trained to administer the treatment and manage the therapy. Ricardo Knight, M.D., M.B.A., who is medical director of the IMAC Regeneration Center of Chicago, is the trials principal investigator.

The Institute of Regenerative and Cellular Medicine serves as the trials independent investigational review board, while Regenerative Outcomes provides management of the study. Further details of the trial can be found at clinicaltrials.gov.

About Bradykinesia Due to Parkinsons Disease

In addition to unusually slow movements and reflexes, bradykinesia may lead to limited ability to lift arms and legs, reduced facial expressions, rigid muscle tone, a shuffling walk, and difficulty with repetitive motion tasks, self-care, and daily activities. Parkinsons disease is the typical culprit of bradykinesia, and as it progresses through its stages, a persons ability to move and respond declines.

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According to Zion Market Research, the global Parkinsons disease therapeutics market was $2.61 billion in 2018 and is expected to grow to $5.28 billion by 2025. The Parkinsons Disease Foundation estimates that nearly 10 million people are suffering from Parkinsons disease, and almost 60,000 new cases are reported annually in the U.S.

About IMAC Holdings, Inc.

IMAC Holdingsowns and manages health and wellness centers that deliver sports medicine, orthopedic care, and restorative joint and tissue therapies for movement restricting pain and neurodegenerative diseases.IMACis comprised of three business segments: outpatient medical centers, The Back Space, and a clinical research division. With treatments to address both young and aging populations,IMAC Holdingsowns or manages outpatient medical clinics that deliver regenerative rehabilitation services as a minimally invasive approach to acute and chronic musculoskeletal and neurological health problems. IMACs The Back Company retail spinal health and wellness treatment centers deliver chiropractic care within Walmart locations. IMACs research division is currently conducting a Phase I clinical trial evaluating a mesenchymal stem cell therapy candidate for bradykinesia due to Parkinsons disease. For more information visitwww.imacholdings.com.

# # #

Safe Harbor Statement

This press release contains forward-looking statements. These forward-looking statements, and terms such as anticipate, expect, believe, may, will, should or other comparable terms, are based largely on IMAC's expectations and are subject to a number of risks and uncertainties, certain of which are beyond IMAC's control. Actual results could differ materially from these forward-looking statements as a result of, among other factors, risks and uncertainties associated with its ability to raise additional funding, its ability to maintain and grow its business, variability of operating results, its ability to maintain and enhance its brand, its development and introduction of new products and services, the successful integration of acquired companies, technologies and assets, marketing and other business development initiatives, competition in the industry, general government regulation, economic conditions, dependence on key personnel, the ability to attract, hire and retain personnel who possess the skills and experience necessary to meet customers requirements, and its ability to protect its intellectual property. IMAC encourages you to review other factors that may affect its future results in its registration statement and in its other filings with the Securities and Exchange Commission. In light of these risks and uncertainties, there can be no assurance that the forward-looking information contained in this press release will in fact occur.

IMAC Press Contact:

Laura Fristoe

lfristoe@imacrc.com

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IMAC Holdings, Inc. Announces Completion of Third Cohort of its Phase 1 Clinical Study of Umbilical Cord-Derived Mesenchymal Stem Cells for the...

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Spinal Muscular Atrophy: Causes and importance of early diagnosis for proactive management – Firstpost

By daniellenierenberg

A person with SMA may find it challenging to stand up, walk, control their head movements, and in some cases, even breathe and swallow

Spine. Image courtesy Pearson Scott Foresman/Wikimedia Commons

Spinal muscular atrophy (SMA) is a severe genetic condition that targets motor neurons in the central nervous system (CNS), resulting in progressive muscle atrophy, weakness, and paralysis. It is a group of genetic disorders in which a person cannot control the movement of their muscles due to a loss of nerve cells in the spinal cord and brain stem. A person with SMA may find it challenging to stand up, walk, control their head movements, and in some cases, even breathe and swallow. Some forms of SMA are present at birth, while others develop over time. Some have an impact on life expectancy.

SMA can be clinically divided into five subtypes. The most severe type is SMA type 0, appearbefore birth, can be fatal before or after birth within the first year of life. Type 1 SMA also called infantile-onset, is the most common type of SMA, accounting for 60% cases, which appears in infants and causes them to die or become dependent on a ventilator by the age of two. Children with SMA type 2 are sitters, while those with type 3 can walk on their own for a while before becoming wheelchair-bound. SMA type 4 develops in adults and causes later-life progressive weakness.

SMA is the most frequent cause of death in the infantile age group, occurring in one in 10,000 live births. However, the SMA carrier frequency was 1 in 38 in a recent Indian study. Children with SMA can currently receive supportive care in India that includes assisted ventilation, feeding, physiotherapy, orthotics, and spine stabilization.

What causes SMA?

SMA is caused by a very specific genetic mutation in a gene called theSMN1 gene. SMN is that protein that play a critical role in the survival of the nerve cells that control muscles. (SMN) protein keeps motor neurons healthy and functioning normally. The loss of motor neurons in the spinal cord caused by SMA patients, and insufficient levels of the SMN protein results in skeletal muscle weakness and wasting.

SMA patients gradually lose their ability to control their muscles movement and strength. The muscles closest to the torso and neck are frequently severely affected by the disease. Some SMA patients never sit, stand, or walk. Other signs of SMA include tongue fasciculation, a bell-shaped chest (caused by muscle weakness), weak cough, difficulty breathing , choking or trouble swallowing, weak sucking and labored breathing during feeding.

How is SMA diagnosed?

The diagnosis of spinal muscular atrophy depends on the type of SMA a person has and age of onset. The path to diagnosis for infants and children with more severe forms of SMA frequently starts when a parent or medical professional notices unusual muscle weakness (hypotonia). People with adult-onset SMA types, such as type 4, might begin the diagnosis process after observing minor symptoms like hand tremors.

Physical exam

A physical examination is required to identify the presence of symptoms like muscle weakness or a lack of reflexes in cases where a new-born is not screened for SMA at birth. A primary care physician or a neurologist could perform this.

Family medical history

As part of your or your childs physical examination, a thorough review of the patients family history is necessary to determine whether there have ever been any instances of neuromuscular disease in the family. If the physical examination and family history raise suspicion of SMA, genetic testing will likely be the next step.

Genetic testing

Through molecular genetic testing, which requires a blood sample, SMA is identified. A single gene is examined for mutations linked to a genetic disease in molecular genetic testing.

Importance of early diagnosis

A patient with SMA must first undergo a higher level of cognitive evaluation. The clinician should assess the patient for weakness before concentrating solely on SMA. A muscle biopsy could be the next step in the evaluation to more precisely distinguish between muscle weakness and nerve weakness. Finally, the clinician would probably identify this patients SMA based on the results of the combined muscle biopsy and electrode diagnostics.

If a diagnosis is made early, the individual has access to the tools and the resources that medical science has developed over the last number of years to assist optimal functioning.

The standard method for diagnosing SMA is molecular genetic testing. SMA should be given early consideration in any infant with weakness or hypotonia due to the effectiveness of molecular testing and high frequency of SMA in the hypotonic infant. All other infant causes of hypotonic weakness are included in the differential diagnosis of severe forms of SMA.

SMA is inherited in an autosomal recessive manner. Each pregnancy of a couple who have had a child with SMA has an approximately 25 per cent chance of producing an affected child. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the diagnosis of SMA has been confirmed by molecular genetic testing in an affected family member.

Currently, there are several SMA treatments that have received FDA approval including Risdiplam (Evrysdi), Onasemnogene abeparvovec-xioi (Zolgensma) and Nusinersen (Spinraza). These targeted treatments may prevent the development or slow the progression of some features of SMA.

The severity of the disease varies depending on the type of SMA, with more severe subtypes needing more aggressive treatment. Proactive care and treatment decision-making by the multidisciplinary team and family are of paramount importance.

The author is MBBS, DCH, MRCPCH, Fellowship Pediatric Genetics, Consultant Clinical Geneticist, Salem Genetics Centre. Views are personal.

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Increasing Road Accidents and Fall Injuries among Aged Population Primarily Driving Need for Orthopedic Navigation Systems: Fact.MR Analysis – Yahoo…

By daniellenierenberg

FACT.MR

Over the coming years, the orthopedic navigation systems market is expected to experience significant growth due to rapid technological innovations, introduction of new orthopedic navigation products, rising cases of cardiovascular diseases, increased funding in R&D activities to improve orthopedic navigation product effectiveness, and rise in the prevalence of osteoarthritis.

United States, Rockville MD, Sept. 02, 2022 (GLOBE NEWSWIRE) -- Expanding at a high-value CAGR of 17%, the global demand for orthopedic navigation systems is projected to increase to a valuation of US$ 433.8 million by 2027, predicts Fact.MR, a market research and competitive intelligence provider.

By expressing three-dimensional computer images in comparative patient analysis, which is a feature of image-guided surgical systems, the orthopedic navigation system integrates information from pre-operative planning and intra-operative execution. These computer workstations for image-guided surgery include a surgical planning and display monitor, image-processing software, and a digitizing system.

As a result of bone spine damage to the spinal nerves, spinal cord, or neurological injury weakening, spinal injuries are the primary cause of mortality and morbidity. To reduce long-term functional disability, prompt medical and surgical care is essential, thereby driving the need for orthopedic navigation systems.

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Effective Results of Computer-assisted Navigation Systems

Other elements anticipated to influence the industry's revenue include associated benefits of computer-assisted surgeries (CAS), including low blood loss, shorter hospital stays, and simpler recovery.

Accurate implant alignment is made possible by CAS, which also enhances functioning, and quality-adjusted life years, and causes reduced discomfort, tissue damage, and problems.The aforementioned reasons are behind therising demand for minimally-invasive surgeries.

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Another factor that is anticipated to increase orthopedic navigation system demand is the development of technology in orthopedic surgical navigation procedures, as well as the rising prevalence of osteoarthritis, and increased investments in R&D.

Key Takeaways from Market Study

Demand for orthopedic navigation systems is expected to surge at a CAGR of 17% from 2022 to 2027.

Global orthopedic navigation system sales areanticipated to be driven by an increase in the use of minimally-invasive procedures and navigation software by doctors and surgeons due to the availability of affordable orthopedic navigationsolutions and greater awareness.

In terms of technology, optical navigation systems are superior to electromagnetic (EM) systems because they expose users to less radiation and provide greater accuracy during difficult operations, allowing surgeons to move accurately through the anatomy of a patient.

Sales of optical navigation systems are expected to balloon at a CAGR of 19% from 2022 to 2027.

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Winning Strategy

Top manufacturers of orthopedic navigation systems are concentrating on raising knowledge about these systems as well astheiruse and advantages among patients and medical professionals alike. By providing Continual Medical Education (CME) sessions, manufacturers of surgical navigation solutionsin developed nations have started to reach out to local communities.

As a result, more doctors and specialists are aware of the existence and application of orthopedic navigation systems. Furthermore, the 6- to 7-year warranty on commercially available orthopedic navigation devicesmakes the entire product sales cycle 7 years.

The market for orthopedic navigation systems is anticipated to expand rapidly over the forecast period due to increasing demand for technological assistance in orthopedic therapies.

Robotic-assisted surgical navigation robot NaoTrac was given CE mark clearance by Taiwan-based firm Brain Navi Biotechnology in November 2021. The company specialises in cutting-edge navigation robots.

Acuson Freestyle Elite ultrasound system, which can be used in conjunction with Artis angiography devices to provide quick and simple ultrasound guidance during interventional procedures, was introduced by Siemens Healthineers in March 2017.

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Segmentation of Orthopedic Navigation Systems Industry Research

By Technology :

Electromagnetic

Optical

Radiography

Others

By Application :

Knee

Spine

Hip

Joint Replacement

Others

By End User :

By Region :

North America

Latin America

Europe

East Asia

South Asia & Oceania

MEA

More Valuable Insights on Offer

Fact.MR, in its new offering, presents an unbiased analysis of the global orthopedic navigation systems market, presenting historical demand data (2017-2021) and forecast statistics for the period of 2022-2027.

The study divulges essential insights on the market on the basis of technology (electromagnetic, optical, radiography, others), application (knee, spine, hip, joint replacement, others), and end user (hospitals, clinics, ambulatory surgical centers, others), across five major regions of the world (North America, Europe, Asia Pacific, Latin America, and MEA).

Check out more related studies published by Fact.MR Research:

Orthopedic Braces and Support System Market:The global orthopedic braces and support system market was valued at aroundUS$ 3 Bnin 2020, which amounts to around11%share of the overall orthopedic devices market. Sales of orthopedic braces and support systems are slated to accelerate at a CAGR of6%to topUS$ 5.5 Bnby 2031. Demand for knee braces and supports is set to increase at a CAGR of5%across the assessment period of 2021 to 2031.

Orthopedic Power Tools Market:The global orthopedic power tools market is estimated atUSD 2.2 Billionin 2022 and is forecast to surpassUSD 3.5 Billionby 2032, growing at a CAGR of4.8%from 2022 to 2032.North America orthopedic power tools market accounts for the largest market share of24.8%.The escalating online presence of players with a strong distribution network coupled with well-established healthcare infrastructure is one of the key factors fueling the market growth.

Orthopedic Footwear Market:The global orthopedic footwear market is majorly driven by rise in the number of accidents, which is the major cause of orthopedic injury. In addition to this, increase in the availability as well as variability of orthopedic footwear in various applications also promotes the market growth. In context of this, about 6% of the U.S. population has foot injuries, bunions and flat feet or fallen arches each year. About 60% of U.S. population older than 17 are suffering from foot and ankle related injuries, sprains and strains of the ankle.

Bone Biopsy Systems Market:The global bone biopsy systems market is set to enjoy a valuation ofUS$ 227.6 millionin 2022 and expand at aCAGR of 6%to reachUS$ 408.9 millionby the end of 2032.Sales of bone biopsy systems accounted for more than30%of the global bone biopsy market at the end of 2021.Bone biopsy and bone marrow biopsy sampling have been one of the most painful experiences for patients. Efforts towards reducing this pain has led to the development of powered bone biopsy systems with increased efficiency.

Bone Marrow Processing Systems Market:A bone marrow processing system is a functionally closed, sterile system designed for automatically isolating and concentrating stem cells derived from donated bone marrow aspirate. Rising applications of bone marrow transplant procedures and bone marrow donation procedures used in the treatment of bone marrow cancers, such as acute leukemia, multiple myeloma, immune deficiency disorders, aplastic anemia, spinal fusions, lymphomas, non-union fractures, osteonecrosis and other rare genetic diseases of the bone marrow, is the primary driver in the market.

Bone Growth Stimulator Market:Bone growth stimulator market was nearly worthUS$ 1.8Bn in 2020 and is anticipated to expand1.6xover the forecast period, anticipated to reach a valuation ofUS$ 3Bn by 2031. In the short-run, bone growth stimulators revenue is likely to topUS$ 1.9Bn by 2022.The market for bone growth stimulators is dominated by North America. This is mostly due to the region's expanding elderly population and the growing burden of orthopedic illnesses. As of 2031, the U.S is expected to register a CAGR worth 5%.

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Increasing Road Accidents and Fall Injuries among Aged Population Primarily Driving Need for Orthopedic Navigation Systems: Fact.MR Analysis - Yahoo...

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Culture of human nasal olfactory stem cells and their extracellular vesicles as advanced therapy medicinal products – Newswise

By daniellenierenberg

Abstract: The olfactory ecto-mesenchymal stem cell (OE-MSC) are mesenchymal stem cells originating from the lamina propria of the nasal mucosa. They have neurogenic and immune-modulatory properties and showed therapeutic potential in animal models of spinal cord trauma, hearing loss, Parkinsons disease, amnesia, and peripheral nerve injury. In this paper we designed a protocol that meet the requirements set by human health agencies to manufacture these stem cells for clinical applications. Once purified, OE-MSCs can be used per se or expanded in order to get the extracellular vesicles (EV) they secrete. A protocol for the extraction of these vesicles was validated and the EV from the OE-MSC were functionally tested on an in vitro model. Nasal mucosa biopsies from three donors were used to validate the manufacturing process of clinical grade OE-MSC. All stages were performed by expert staff of the cell therapy laboratory according to aseptic handling manipulations, requiring grade A laminar airflow. Enzymatic digestion provides more rapidly a high number of cells and is less likely to be contaminated. Foetal calf serum was replaced with human platelet lysate and allowed stronger cell proliferation, with the optimal percentage of platelet lysate being 10%. Cultivated OE-MSCs are sterile, highly proliferative (percentage of CFU-F progenitors was 15,5%) and their maintenance does not induce chromosomal rearrangement (karyotyping and chromosomal microarray analysis were normal). These cells express the usual phenotypic markers of OE-MSC. Purification of the EVs was performed with ultracentrifugation and size exclusion chromatography. Purified vesicles expressed the recognized markers of EVs (Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines) and promoted cell differentiation and neurite elongation in a model of neuroblastoma Neuro2a cell line. We developed a safer and more efficient manufacturing process for clinical-grade olfactory stem cells, these cells can now be used in humans. A phase I clinical trial will begin soon. An efficient protocol for the purification of the OE-MSC EVs have been validated. These EVs exert neurogenic properties in vitro. More studies are needed to understand the exact mechanisms of action of these EVs and prove their efficacy and safety in animal models.

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Curious kids: what is inside teeth? – The Conversation

By daniellenierenberg

What is inside teeth? Nicholas, age 5, Australian Capital Territory

Great question, Nicholas. It is important for us to know whats inside teeth as they help us eat, and eating gives us the energy to do our daily activities.

Our teeth are not just for chewing, though. We also need teeth for speaking, because different teeth contribute to different sounds. For example, we need upper front teeth to speak words starting with f or v sounds.

The teeth in the upper jaw are called as maxillary or upper teeth, and those on the lower jaw are called as mandibular or lower teeth. Then each jaw has two side-to-side halves. All up, thats four quadrants of teeth.

We have two sets of teeth. There are 20 teeth in the first set. We commonly call these milk teeth or primary teeth. They start forming while we are in the womb, even before we are born! The first one starts coming out of the gums when we are six months old, and most people have all their milk teeth by the age of three.

We keep our milk teeth until we are six years old, when we start losing them and the adult teeth or permanent teeth start coming in. By 14 or 15 years of age, most of us will have all our adult teeth except the last tooth in each side of the jaws. Some people call these wisdom teeth. There are 32 teeth in an entire adult set, with an equal number of teeth on each side.

We have four different types of teeth:

Read more: Curious Kids: what is brain freeze?

Each tooth can be divided into two parts. The crown is the part of the tooth we can see in the mouth, while the root sits within the gum and bone of the jaw. Some teeth have more than one root.

And each tooth has two layers: enamel and dentine, with pulp at the centre which has nerves and blood. Roots do not have enamel but another layer called cementum.

Enamel is the hardest substance in the body and protects the dentine and pulp, just like a helmet protects your head.

Dentine is the second layer and makes up most of the tooth.

We feel pain in the tooth when the innermost part, pulp, is involved.

Scientists have been working hard to find how special cells called stem cells in pulp could be used to repair other parts of the teeth, gums and even other body parts such as the spinal cord, brain and heart.

Read more: Curious kids: why dont whales have teeth like we do?

Hopefully youve already got into the habit of brushing twice every day with a fluoridated toothpaste for at least two minutes.

Tooth decay is caused by germs that love to feast on sugary or treat food in our mouth. We can stop that happening by saving lollies and sweets for special occasions and cleaning every tooth really well.

When teeth are not well cared for, they can develop tooth decay, which could cause pain when it involves that pulp deep inside your teeth. Its important to visit an oral health professional (such as your family dentist or hygienist) regularly. They can tell you how to take good care of your teeth and treat damaged teeth when required.

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Curious kids: what is inside teeth? - The Conversation

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Human placental mesenchymal stem cells derived exosomes improved functional recovery via attenuating apoptosis and increasing axonal regeneration…

By daniellenierenberg

Abstract: Background Spinal cord injury (SCI) due to lack of restoration of damaged axons is associated with sensorimotor impairment. This study was focused on using the human Placental mesenchymal stem cells- exosome (hPMSCs- exosomes) in an animal model of severe SCI under a new myelogram protocol to confirm lumbar puncture (LP) injection accuracy and evaluate intrathecal space. Methods Mesenchymal stem cells (MSC) were extracted from human placenta tissue and were characterized. HPMSCs- exosomes were isolated by ultracentrifuge. After creating the severe SCI model, LP injection of exosomes was performed in the acute phase. Myelogram was also employed. The improved functional recovery of the animals in the treatment and control groups was followed by recording movement scores for 6 weeks. Hematoxylin-Eosin (H&E) staining was used to evaluate to detect pathological changes and glial scar size. The Immunohistochemistry (IHC) of GFAP and NF200 factors as well as the apoptosis tunnel test was investigated in the tissue samples from the injury site Results The results demonstrated that the use of the myelogram can be a feasible, appropriate and cost-effective method to confirm the accuracy of therapeutic agents LP injection and examine the subarachnoid space in the model of laboratory animals. Furthermore, intrathecal injection of hPMSCs-exosomes in the acute phase of SCI can improve motor function by attenuating apoptosis of neurons at the site of injury, decreased GFAP expression and increased NF200 in the treatment group, reducing glial scarring, and increasing axonal regeneration. Improving functional recovery by not creating bedsores in the treatment group and preventing hematuria were other effects of the exosome Conclusions In conclusion, the effects of hPMSCs-exosome can be considered to be not only in restoring function but also in preventing complications and managing symptoms. Thus, the neuroregenerative and anti-apoptotic potential of hPMSCs-exosome can be considered a therapeutic approach in SCI reconstructive medicine.

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Human placental mesenchymal stem cells derived exosomes improved functional recovery via attenuating apoptosis and increasing axonal regeneration...

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How the Regenerative Properties of Glioblastoma Can Be Terminated – Gilmore Health News

By daniellenierenberg

Glioblastoma multiforme (GBM) or simply glioblastoma, is a type of cancer characterized by the growth of an aggressive neoplasm (tumor) in the brain or spinal cord. This type of cancer often occurs in older adults, although the younger population may also be affected.

Read Also: Targeting Hox Gene Dysregulation a Promising Approach for the Treatment of Glioblastoma Multiforme

Glioblastoma

This cancer type is known to be difficult to treat because of its high tendency to reoccur in patients, even after the combination of the three known procedures to treat cancers: surgery, radiotherapy, and chemotherapy. Glioblastoma has been a thorn in the flesh in the world of medicine amongst all cancer types due to the low survival rate of patients affected by it (average survival of 18 months, with only 5% of patients living up to five years). The following factors make this possible: no specific signs or symptoms are noticed leading to late diagnosis and the ability of the cancer cells to resist treatment procedures (the major factor).

Studies have been ongoing to uncover the mechanism behind this major factor, and it has been revealed that Glioblastoma multiforme contains a functional subset of cells known as glioblastoma stem-like cells (GSCs) which are the brain behind its reoccurrence capacity. The identity of these cells remained hidden until a recent study done by a group of scientists finally uncovered it.

Read Also: Brain Cancer: A Promising New Treatment for Destroying Aggressive Glioblastoma Cell

The team found out that these functional subsets of cells can be identified through singular mitochondrial alternative metabolisms. After intensively studying the metabolic reactions of these cells, they developed a tumor model that possessed the features of the GBM cultured in the lab. This way, they discovered that GSCs use these two metabolic reactions alpha-ketoglutarate reductive carboxylation and pyruvate carboxylation within their cells. They also discovered that these reactions are catalyzed by the enzymes isocitrate dehydrogenase and pyruvate carboxylase respectively.

They were able to uncover that their high rate of survival which facilitated the recurrence of the tumor is linked to the pyruvate carboxylation reaction. This discovery is important as it means that doctors may now be able to tackle the reoccurring ability of the tumor effectively.

It has always been known that treating glioblastoma is difficult due to its high recurring ability. However, with the revelation from this study, it is now possible for physicians to come up with more effective treatment procedures that would result in a reduced recurrence of the tumors, and an increased survival rate of patients.

This study raises the hopes of both physicians and patients as it reveals a way to hinder the recurrence of glioblastoma tumors. More research is still ongoing to hasten the innovation of a more effective treatment technique.

Read Also: Brain Cancer: Researchers Reprogram Immune Cells to Improve the Effectiveness of Treatment

Pyruvate carboxylation identifies Glioblastoma Stem-like Cells opening new metabolic strategy to prevent tumor recurrence

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How the Regenerative Properties of Glioblastoma Can Be Terminated - Gilmore Health News

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New TSXV listing looks to address the $3B spinal cord injury treatment market (NRX.V) – FXStreet

By daniellenierenberg

The company is developing a novel, non-invasive, bio-guided treatment to restore function of patients with acute spinal cord injuries.

Over two hundred and fifty thousand people suffer from spinal cord injuries in the US every year, with patients typically experiencing major, and mostly irreversible, loss of function that requires millions of dollars in lifetime care per patient.

NurExone is developing a revolutionary bio-guided treatment. The technology is based on exosomes, small particles that are created when stem cells proliferate, to deliver therapeutic agents to a specific location in the body. Nurexones proprietary agents, delivered by the exosomes, create an environment may support Nerves regeneration. For spine injuries, the bio-guided treatment is an agent that inhibits the PTEN protein in nerve cells, allowing nerves regeneration to occur.

The company carried out preclinical, animal studies that demonstrated that bio-guided treatment led to significant improvement, sensory recovery, and faster reflex restoration. The study reveals that Nurexones proprietary technology caused new connections in the spinal cord, repairing the damage from injuries, at least in part.

Studies also suggested that Nurexones technology may be useful for other indications including strokes and traumatic brain injuries (TBI).

The company was founded in 2020, based on research by Professor Shulamit Levenberg, Head of the Biomedical Engineering Department at Technion, and by Professor Daniel Offen, Head of the Lab for Neurosciences at the Felsenstein Medical Research Center in Tel Aviv University.

Spine related injuries are expected to increase in the future owing to motor accidents, workplace injuries, stroke, and cancer related motor disabilities. Currently, between 250,000 and 500,000 people become spinal cord injured every year worldwide, and the lifetime costs of treatments range from $1.6 million to nearly $5 million for 25-year-olds, to $1.1 million to nearly $2.7 million for 50-year-olds. The total addressable market for spinal cord trauma injuries is expected to reach $3.04 billion by 2025, with a CAGR of 3.7%.

Stepping back to look solely at exosome technology (not necessarily related to SCI), since 2018, exosomes are an emerging therapeutic field, with hundreds of millions of US dollars invested in exosome technologies by companies including Eli Lilly, Roche, and Takeda.

NurExone has obtained exclusive rights to an advanced exosome manufacturing process developed at the Technion, Israel Institute of Technology, Haifa. NurExone will be responsible for additional exosome research, management of clinical studies and commercialization of the technology for different indications not limited to Central Nerve System (CNS).

NurExones listing on the TSX.V under the symbol NRX was accomplished through an agreed reverse takeover (RTO) of EnerSpar signed on January 3, 2022. EnerSpar will acquire each ordinary share of NurExone in exchange for 17 post-consolidation EnerSpar shares, resulting in a total of 48,383,963 total shares outstanding following completion of the transaction.

Despite limited financial analyses available on the stock, it seems like a potentially unique opportunity given the fact that the market for spinal-cord treatment continues to grow, thus enabling new players in the field to partake in this ever-growing industry. Moreover, any company that delivers therapy that has the potential to unlock the secret of restoring function to patients who have experienced traumatic spinal injury, seems to be worth considering

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New TSXV listing looks to address the $3B spinal cord injury treatment market (NRX.V) - FXStreet

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Human iPSC co-culture model to investigate the interaction between microglia and motor neurons | Scientific Reports – Nature.com

By daniellenierenberg

Ethics statement

All human material (blood RNA, primary microglia RNA, iPSCs) used in this study was derived after signed informed consent: for blood, according to University of Oxford OHS policy document 1/03; all procedures related to the use of the primary microglia followed established institutional (McGill University, Montreal, QC, Canada) and Canadian Institutes of Health Research guidelines for the use of human cells; for iPSC, with approval from the South Central Berkshire Research Ethics Committee, U.K. (REC 10/H0505/71). The blood RNA and primary microglia RNA samples have been published previously26, as have the iPSC lines (see below).

Four healthy control iPSC lines, SFC840-03-03 (female, 67years old,35), SFC841-03-01 (male, 36,18), SFC856-03-04 (female, 78,36), OX3-06 (male, 49,37), generated from skin biopsy fibroblasts and characterized as described before, were used in this study. Additionally, the previously reported26 line AH016-3 Lenti_IP_RFP (male, 80years old), which constitutively expresses Red Fluorescent Protein (RFP) under continuous puromycin selection, was used for some live-imaging experiments.

iPSCs were cultured in mTeSR1 (StemCell Technologies) or OXE8 medium38 on Geltrex (Thermo Fisher)-coated tissue culture plates with daily medium changes. Passaging was done as clumps using EDTA in PBS (0.5mM). Cells were initially expanded at low passage to create a master stock, which was used for all experiments to ensure consistency. Cells were regularly tested negative for mycoplasma using MycoAlert Mycoplasma Detection Kit (Lonza).

iPSCs were differentiated to MNs according to our previously published protocol18,19,27. Briefly, neural induction of iPSC monolayers was performed using DMEM-F12/Neurobasal 50:50 medium supplemented with N2 (1X), B27 (1X), 2-Mercaptoethanol (1X), AntibioticAntimycotic (1X, all ThermoFisher), Ascorbic Acid (0.5M), Compound C (1M, both Merck), and Chir99021 (3M, R&D Systems). After two days in culture, Retinoic Acid (RA, 1M, Merck) and Smoothened Agonist (SAG, 500nM, R&D Systems) were additionally added to the medium. Two days later, Compound C and Chir99021 were removed from the medium. After another 5days in culture, neural precursors were dissociated using accutase (ThermoFisher), and split 1:3 onto Geltrex-coated tissue culture plates in medium supplemented with Y-27632 dihydrochloride (10M, R&D Systems). After one day, Y-27632 dihydrochloride was removed from the medium, and then the cells were cultured for another 8days with medium changes every other day. For terminal maturation, the cells were dissociated on day in vitro (DIV) 18 using accutase and plated onto coverslips or tissue culture plates coated with polyethylenimine (PEI, 0.07%, Merck) and Geltrex or tissue culture dishes coated with PDL (Sigma-Aldrich)/ Laminin (R&D Systems)/ Fibronectin (Corning). For this step, the medium was additionally supplemented with BDNF (10ng/mL), GDNF (10ng/mL), Laminin (0.5g/mL, all ThermoFisher), Y-27632 dihydrochloride (10M), and DAPT (10M, R&D Systems). Three days later, Y-27632 dihydrochloride was removed from the medium. After another three days, DAPT was removed from the medium. Full medium changes were then performed every three days.

For MNs differentiated in co-culture medium alone, all steps were performed similarly until three days after the terminal re-plating (D21). MNs were then cultured in co-culture medium as described below.

iPSCs were differentiated to macrophage/microglia precursors as described previously20,21. Briefly, embryoid body (EB) formation was induced by seeding iPSCs into Aggrewell 800 wells (STEMCELL Technologies) in OXE838 or mTeSR1 medium supplemented with Bone Morphogenetic Protein 4 (BMP4, 50ng/mL), Vascular Endothelial Growth Factor (VEGF, 50ng/mL, both Peprotech), and Stem Cell Factor (SCF, 20ng/mL, Miltenyi Biotec). After four days with daily medium changes, EBs were transferred to T175 flasks (~150 EBs each) and differentiated in X-VIVO15 (Lonza), supplemented with Interleukin-3 (IL-3, 25ng/mL, R&D Systems), Macrophage Colony-Stimulating Factor (M-CSF, 100ng/mL), GlutaMAX (1X, both ThermoFisher), and 2-Mercaptoethanol (1X). Fresh medium was added weekly. After approximately one month, precursors emerged into the supernatant and could be harvested weekly. Harvested cells were passed through a cell strainer (40M, Falcon) and either lysed directly for RNA extraction or differentiated to microglia in monoculture or co-culture as described below.

Three days after the final re-plating of differentiating MNs (DIV21), macrophage/microglia precursors were harvested as described above and resuspended in co-culture medium comprised of Advanced DMEM-F12 (ThermoFisher) supplemented with GlutaMAX (1X), N2 (1X), AntibioticAntimycotic (1X), 2-Mercaptoethanol (1X), Interleukin-34 (IL-34, 100ng/mL, Peprotech), BDNF (10ng/mL), GDNF (10ng/mL), and Laminin (0.5g/mL). MNs were quickly rinsed with PBS, and macrophage/microglia precursors re-suspended in co-culture medium were added to each well. Co-cultures were then maintained for at least 14days before assays were conducted as described below. Half medium changes were performed every 23days.

For comparisons between co-cultures and monocultures, MNs and monocultured microglia were also differentiated alone in co-culture medium.

Cells cultured on coverslips were pre-fixed with 2% paraformaldehyde in PBS for 2min and then fixed with 4% paraformaldehyde in PBS for 15min at room temperature (RT). After permeabilization and blocking with 5% donkey/goat serum and 0.2% Triton X-100 in PBS for 1h at RT, the coverslips were incubated with primary antibodies diluted in 1% donkey/goat serum and 0.1% Triton X-100 in PBS at 4C ON. The following primary antibodies were used: rabbit anti-cleaved caspase 3 (1:400, 9661S, Cell Signaling), mouse anti-ISLET1 (1:50, 40.2D6, Developmental Studies Hybridoma Bank), mouse anti-TUJ1 (1:500, 801201, BioLegend), rabbit anti-TUJ1 (1:500, 802001, BioLegend), chicken anti-TUJ1 (1:500, GTX85469, GeneTex), rabbit anti-IBA1 (1:500, 019-19741, FUJIFILM Wako Pure Chemical Corporation), goat anti-IBA1 (1:500, ab5076, abcam), rabbit anti-synaptophysin (1:200, ab14692, abcam), goat anti-ChAT (1:100, ab114P, abcam), rat anti-TREM2 (1:100, MAB17291-100, R&D Systems), rabbit anti-TMEM119 (1:100, ab185337, abcam), rat anti-CD11b (1:100, 101202, BioLegend).

After three washes with PBS-0.1% Triton X-100 for 5min each, coverslips were incubated with corresponding fluorescent secondary antibodies Alexa Fluor 488/568/647 donkey anti-mouse/rabbit/rat/goat, goat anti-chicken (all 1:1000, all ThermoFisher). Coverslips were then washed twice with PBS-0.1% Triton X-100 for 5min each and incubated with 4,6-diamidino-2-phenylindole (DAPI, 1g/mL, Sigma-Aldrich) in PBS for 10min. After an additional 5min-washing step with PBS-0.1% Triton X-100, the coverslips were mounted onto microscopy slides using ProLong Diamond Antifade Mountant (ThermoFisher). Confocal microscopy was then performed using an LSM 710 microscope (Zeiss).

For the analysis of neuronal and MN markers after differentiation, three z-stacks (2m intervals) of randomly selected visual fields (425.1425.1m) were taken for each coverslip at 20magnification. The ratios of TUJ1-positive, ChAT-positive, ISLET1-positive, ChAT-positive/ TUJ1-positive, and ISLET1-positive/ TUJ1-positive cells were then quantified using Fiji in a blinded fashion.

For the analysis of microglial markers in monoculture and co-culture, three z-stacks (1m intervals) of randomly selected visual fields (212.55212.55m) were taken for each coverslip at 40magnification. The expression of CD11b, TMEM119, and TREM2 in IBA1-positive cells in monoculture and co-culture was then quantified using Fiji.

For the analysis of apoptosis in neurons, five z-stacks images of randomly selected visual fields (212.55212.55m) were taken at 40magnification for each coverslip. The ratios of cleaved caspase 3/ TUJ1-positive cells were then quantified for neurons in monoculture and co-culture in a blinded fashion. For the analysis of apoptosis in microglia, three z-stacks images of randomly selected visual fields (212.55212.55m) were taken at 40magnification for each coverslip. The ratios of cleaved caspase 3/ IBA1-positive cells were then quantified for microglia in monoculture and co-culture.

For the analysis of microglial ramifications, five z-stacks images of randomly selected visual fields (212.55212.55m) were taken at 40magnification for each coverslip. To analyze the branching of IBA1-positive microglia in monoculture and co-culture, the average branch length, number of branch points and number of branch endpoints was determined using 3DMorph39, a Matlab-based script for the automated analysis of microglial morphology.

From the same harvest, macrophage precursors (pMacpre) were either lysed directly or differentiated to microglia in monoculture (pMGL) or microglia in co-culture with MNs (co-pMG) for 14days. pMGL were rinsed with PBS and directly lysed in the dish. For both pMacpre and pMGL, RNA was extracted using an RNAeasy Mini Plus kit (Qiagen) according to the manufacturers instructions. Co-cultures were first dissociated by 15min incubation with papain (P4762, Sigma-Aldrich) diluted in accutase (20 U/mL) and gentle trituration based on a previously published protocol40. The cell suspension was then passed through a cell strainer (70m, Falcon) to remove cell clumps. To extract co-pMG, magnetic-activated cell sorting (MACS) was then performed using CD11b-MACS beads (130093-634, Miltenyi Biotec) according to the manufacturers instructions. The panned cell population was lysed for RNA extraction using an RNAeasy Micro kit (Qiagen) according to the manufacturers instructions. In addition, RNA from human fetal microglia and blood monocytes from three different healthy genetic backgrounds wasre-used from our previous study26.

RNA from the four different healthy control lines (listed earlier) per condition (pMacpre, pMGL, co-pMG) was used for RNA sequencing analysis. Material was quantified using RiboGreen (Invitrogen) on the FLUOstar OPTIMA plate reader (BMG Labtech) and the size profile and integrity analysed on the 2200 or 4200 TapeStation (Agilent, RNA ScreenTape). RIN estimates for all samples were between 9.2 and 9.9. Input material was normalised to 100ng prior to library preparation. Polyadenylated transcript enrichment and strand specific library preparation was completed using NEBNext Ultra II mRNA kit (NEB) following manufacturers instructions. Libraries were amplified (14 cycles) on a Tetrad (Bio-Rad) using in-house unique dual indexing primers (based on41). Individual libraries were normalised using Qubit, and the size profile was analysed on the 2200 or 4200 TapeStation. Individual libraries were normalised and pooled together accordingly. The pooled library was diluted to~10nM for storage. The 10nM library was denatured and further diluted prior to loading on the sequencer. Paired end sequencing was performed using a NovaSeq6000 platform (Illumina, NovaSeq 6000 S2/S4 reagent kit, v1.5, 300 cycles), generating a raw read count of a minimum of 34M reads per sample.

Further processing of the raw data was then performed using an in-house pipeline. For comparison, the RNA sequencing data (GSE89189) fromAbud et al.28 and the dataset (GSE85839) fromMuffat et al.29 were downloaded and processed in parallel. Quality control of fastq files was performed using FastQC (https://www.bioinformatics.babraham.ac.uk/projects/fastqc/) and MultiQC42. Paired-end reads were mapped to the human GRCh38.p13 reference genome (https://www.gencodegenes.org) using HISAT2 v2.2.143. Mapping quality control was done using SAMtools44 and Picard (http://broadinstitute.github.io/picard/) metrics. The counts table was obtained using FeatureCounts v2.0.145. Normalization of counts and differential expression analysis for the comparison of pMGL and co-pMG was performed using DESeq2 v1.28.146 in RStudio 1.4.1103, including the biological gender in the model and with the BenjaminiHochberg method for multiple testing correction. Exploratory data analysis was performed following variance-stabilizing transformation of the counts table, using heat maps and hierarchical clustering with the pheatmap 1.0.12 package (https://github.com/raivokolde/pheatmap) and principal component analysis. Log2 fold change (log2 fc) shrinkage for the comparison of pMGL and co-pMG was performed using the ashr package v2.2-4747. Genes with |log2 fc|>2 and adjusted p value<0.01 were defined as differentially expressed and interpreted with annotations from the Gene Ontology database using clusterProfiler v3.16.148 to perform over-representation analyses.

Equal amounts of RNA (30ng) were reverse-transcribed to cDNA using the High-Capacity cDNA Reverse Transcription Kit (ThermoFisher) according to the manufacturers instructions. Quantitative real-time PCR was performed with Fast SYBR Green Master Mix (ThermoFisher) according to the manufacturers instructions using a LightCycler 480 PCR System (Roche). The following primers (ChAT from Eurofins Genomics, all others from ThermoFisher) were used:

Quantification of the relative fold gene expression of samples was performed using the 2Ct method with normalization to the GAPDH reference gene.

AH016-3 Lenti-IP-RFP-microglia were co-cultured with healthy control motor neurons in PEI- and Geltrex-coated glass bottom dishes for confocal microscopy (VWR). The RFP signal was used to identify microglia in co-culture. To visualize microglial movement, images of the RFP signal and brightfield were taken every~30s for 1h (22 stitched images, 20magnification) using a Cell Observer spinning disc confocal microscope (Zeiss) equipped with an incubation system (37C, 5% CO2). To image phagocytic activity, co-cultures were rinsed with Live Cell Imaging Solution (1X, ThermoFisher), and pHrodo Green Zymosan Bioparticles Conjugates (P35365, ThermoFisher) diluted in Live Cell Imaging Solution (50g/mL), which become fluorescent upon phagocytic uptake, were added. The dish was immediately transferred to the spinning disc confocal microscope, and stitched images (33, 20magnification) were acquired every 5min for 2h.

To induce pro-inflammatory (M1) or anti-inflammatory (M2) microglial phenotypes, cells were treated with Lipopolysaccharides (LPS, 100ng/mL, Sigma) and Interferon- (IFN-, 100ng/mL, ThermoFisher), or Interleukin-4 (IL-4, 40ng/mL, R&D Systems) and Interleukin-13 (IL-13, 20ng/mL, Peprotech), respectively, for 18h. Vehicle-treated (co-culture medium) cells were used as an unstimulated (M0) control.

To analyze the clustering of microglia upon pro-inflammatory and anti-inflammatory stimulation, RFP-positive microglia were imaged directly before the addition of M1/M2 inducing agents, and at 9h and 18h post-stimulation using the Cell Observer spinning disc confocal microscope (55 stitched images, 10magnification). The number of individual microglial cells and size of microglial clusters was quantified using the analyze particle function in Fiji.

After stimulation with M1/M2-inducing agents, culture supernatants were collected and spun down at 1200g for 10min at 4C. Pooled samples from three different healthy control lines for each cell type were analyzed using the Proteome Profiler Human XL Cytokine Array Kit (R&D Systems) according to the manufacturers instructions. The signal was visualized on a ChemiDoc MP imaging system (Bio-Rad) and analyzed using ImageStudioLite v5.2.5 (LI-COR). Data was then plotted as arbitrary units using the pheatmap 1.0.12 package in RStudio 1.4.1103.

In addition, to confirm the relative expression of Serpin E1 and CHI3L1 in cell culture supernatants, the Human Human Chitinase 3-like 1 Quantikine ELISA Kit (DC3L10) and Human Serpin E1/PAI-1 Quantikine ELISA Kit (DSE100, both R&D Systems) were used according to the manufacturers instructions.

pNeuron, pMGL and co-cultures were plated and maintained in WillCo-dish Glass Bottom Dishes (WillCo Wells) for 14days. Calcium transients were measured using the fluorescent probe Fluo 4-AM according to the manufacturers instructions (ThermoFisher). Cells were incubated with 20M Fluo 4-AM resuspended in 0.2% dimethyl sulfoxide for 30min at RT in Live Imaging Solution (ThermoFisher). After a washing step with Live Imaging Solution, cells were allowed to calibrate at RT for 1520min before imaging. Ca2+ images were taken by fluorescence microscopy at RT. The dye was excited at 488nm and images were taken continuously with a baseline recorded for 30s before stimulation. The stimuli used for calcium release were 50mM KCl (Sigma-Aldrich) for 30s, followed by a washing step for one minute. Microglial calcium release was stimulated by 50M ADP (Merck) under continuous perfusion for 1min, followed by a 1-min wash. Analysis of fluorescence intensity was performed using Fiji. Fluorescence measurements are expressed as a ratio (F/Fo) of the mean change in fluorescence (F) at a pixel relative to the resting fluorescence at that pixel before stimulation (Fo). The responses were analysed in 2040 cells per culture.

MNs on DIV 3345 were maintained in a bath temperature of 25C in a solution containing 167mM NaCl, 2.4mM KCl, 1mM MgCl2, 10mM glucose, 10mM HEPES, and 2mM CaCl2 adjusted to a pH of 7.4 and 300mOsm. Electrodes with tip resistances between 3 and 7M were produced from borosilicate glass (0.86mm inner diameter; 1.5mm outer diameter). The electrode was filled with intracellular solution containing 140mMK-Gluconate, 6mM NaCl, 1mM EGTA, 10mM HEPES, 4mM MgATP, 0.5mM Na3GTP, adjusted to pH 7.3 and 290mOsm. Data acquisition was performed using a Multiclamp 700B amplifier, digidata 1550A and clampEx 6 software (pCLAMP Software suite, Molecular Devices). Data was filtered at 2kHz and digitized at 10kHz. Series resistance (Rs) was continuously monitored and only recordings with stable<50 M and Rs<20% were included in the analysis. Voltage gated channel currents were measured on voltage clamp, neurons were pre-pulsed for 250ms with 140mV and subsequently a 10mV-step voltage was applied from 70 to+70mV. Induced action potentials were recorded on current clamp, neurons were held at 70mV and 8 voltage steps of 10mV, from 10 to 60mV, were applied. Data was analyzed using Clampfit 10.7 (pCLAMP Software suite).

Statistical analyses were conducted using GraphPad Prism 9 (GraphPad Software, San Diego, California USA, http://www.graphpad.com). Comparisons of two groups were performed by two-tailed unpaired t-tests and multiple group comparisons by one-way or two-way analysis of variance (ANOVA) with appropriate post-hoc tests as indicated in the figure legends. The statistical test and number of independent experiments used for each analysis are indicated in each figure legend. Data are presented as single data points and meansSEM. Differences were considered significant when P<0.05 (*P<0.05; **P<0.01; ***P<0.001; ns: not significant). GraphPad Prism 9 or RStudio 1.4.1103 were used to plot data. Final assembly and preparation of all figures was done using Adobe Illustrator 25.4.1.

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Human iPSC co-culture model to investigate the interaction between microglia and motor neurons | Scientific Reports - Nature.com

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Negligence in treatment of diseases like glioblastoma can be fatal, seminar told – The News International

By daniellenierenberg

Glioblastoma (GBM) is a fast-growing type of central nervous system tumour that forms from glial (supportive) tissue of the brain and spinal cord, with cells that look very different from normal ones, said Dr Ata Ul Aleem Bhatti, ex-instructor neurosurgeon, Aga Khan University Medical College, Dar as Salaam, Tanzania, and consultant neurosurgeon at the South City Hospital, Karachi.

Addressing a public awareness seminar on World GBM Day 2022 in collaboration with the Neurospinal & Cancer Care Postgraduate Institute, he said: Like most brain tumors, GBM grow more rapidly than their benign counterparts and affect the brain in many different ways depending on the part of the brain they are located.

Dr Bhatti further explained: Unfortunately, like most cancers in other parts of the body, the exact cause of GBM is unknown. Glioblastoma itself is not the only form of brain cancer, though it is the most common and most aggressive type. Other malignant brain tumours include medulloblastomas, lymphomas and anaplastic astrocytomas, to mention a few.

Various risk factors linked to developing cancer in the brain include over exposure to radiation and some rare inherited conditions. In all of these cases, the exact connection or link remains a mystery, but we do see a pattern of occurrence.

Again, unfortunately, there are no symptoms that will immediately tell someone they are developing a malignant brain tumour, however, there are some common things to look out for, when a person develops a mass or growth in the brain, either benign or malignant. These include a bad headache, but not the type one gets after spending hours in Karachi traffic or a stressful day. This headache is usually worse in the morning and persistent over several weeks. It may be associated with a feeling of wanting to vomit (nausea) or actually vomiting, which tends to make the person feel better.

Unfortunately, according to Dr Bhatti, at the moment there is no cure for brain cancers. While there are many therapies that are being tried and a lot of experimental work going on, we are yet to find a cure.

Malignant brain tumours are usually treated with a combination of surgery, radiotherapy and chemotherapy.

Sometimes, newer options like hormone therapy, immune therapy and others are also used. Which option is offered depends on the type of cancer involved. Surgery remains a main part of any treatment regime for GBM, since it allows for accurate diagnosis and also reduces the amount of tumour the body has to fight against.

In some cases, an attempt is made to remove as much of the tumour as possible to allow the radiotherapy and chemotherapy be more effective.

Dr Adeel Ahmed Memon, consultant clinical & radiation oncologist and assistant professor at the Karachi Institute of Radiotherapy & Nuclear Medicine (KIRAN), gave a radiation oncologist perspective for GBM.

Radiosurgery is a treatment method that uses specialized radiation delivery systems to focus radiation at the site of the tumor, while minimizing the radiation dose to the surrounding brain. Radiosurgery may be used in selective cases for tumor recurrence, often using additional information derived from MRS or PET scans, he said.

Studies have shown that radiation therapy provides most patients with improved outcomes and longer survival rates when given the combination of surgery, radiation and chemotherapy compared with surgery alone. Radiation also may be used as the sole treatment when a glioblastoma tumor is in an area that is not appropriate for surgery.

Guest speaker Dr Reena Kumari, consultant medical oncologist & assistant professor at Dr Ziauddin University Hospital, also shared her views regarding the role of chemotherapy, targeted & immunotherapy and discussed why GBM was difficult to treat brain tumor.

When treating GBM, she explained, what makes treatment challenging is that you have tumor cells that are not active, meaning they are dormant. These cells are known as cancer stem cells and since they are not active they do not die by radiation and chemotherapy.

Unlike other cancers such as breast or lung, brain tumors are extremely genetically heterogeneous means there is a high degree of variation within the same tumor cells that makes each individual glioblastoma molecularly distinct. This can be challenging when predicting prognosis and treatment, if it is in an area which is difficult access, or too close to major blood vessels or other important centers of the brain, it can make surgery tough, tendency of the tumor to come back aggressively is also a great challenge.

A promising targeted treatment is the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab. It has been approved by FDA for several different types of cancer, including. Angiogenesis is a key survival feature of many cancers as tumors rely on nutrients from the vasculature to proliferate

A clinical trial has found that selinexor, the first of a new class of anti-cancer drugs called selective inhibitors of nuclear export (SINE) , is able to shrink tumors in almost a third of patients with recurrent glioblastoma,

Dr Kumari urged people to be careful, saying: Negligence in treatment of diseases like GBM can be fatal. She further said that timely treatment of brain tumor was very important as chances of relapsing increases with the grade of tumor.

Dr Sadia Afsar, in-Charge, Neurosurgery Department, Abbasi Shaheed Hospital , highlighted the problems faced by patients with GBM and other brain tumors as this is ignored by community.

Government needs to realise that these conditions are quite common and provide more facilities for early diagnosis and treatment of GBM & other types of brain tumors like MRI, CT-Scan & PET-CT Scanner must be readily available across the country to enhance diagnosis.

The scarcity of Radiotherapy modalities in the country has already been highlighted by her and said that a huge time is wasted in long queue, additionally. The teaching hospitals need to also be equipped to perform proper neurosurgery department and OT, as this is the first step in any treatment programme for brain tumors, including GMBs.

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Negligence in treatment of diseases like glioblastoma can be fatal, seminar told - The News International

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What lab-grown cerebral organoids are revealing about the brain – New Scientist

By daniellenierenberg

Blobs of human brain cells cultivated in the lab, known as brain organoids or mini-brains, are transforming our understanding of neural development and disease. Now, researchers are working to make them more like the real thing

By Clare Wilson

Neil Webb

A DOZEN tiny, creamy balls are suspended in a dish of clear, pink liquid. Seen with the naked eye, they are amorphous blobs. But under a powerful microscope, and with some clever staining, their internal complexity is revealed: intricate whorls and layers of red, blue and green.

These are human brain cells, complete with branching outgrowths that have connected with one other, sparking electrical impulses. This is the stuff that thoughts are made of. And yet, these collections of cells were made in a laboratory in this case, in the lab of Madeline Lancaster at the University of Cambridge.

The structures, known as brain organoids or sometimes mini-brains, hold immense promise for helping us understand the brain. They have already produced fresh insights into how this most mysterious organ functions, how it differs in people with autism and how it goes awry in conditions such as dementia and motor neurone disease. They have even been made to grow primitive eyes.

To truly fulfill the potential of mini-brains, however, neuroscientists want to make them bigger and more complex. Some are attempting to grow them with blood vessels. Others are fusing two organoids, each mimicking a different part of the brain. Should they succeed, their lab-grown brains could model development and disease in the real thing in greater detail than ever before, paving the way to new insights and treatments.

But as researchers seek to make mini-brains genuinely worthy of the name, they move ever closer to a crucial question: at what point will their creations approach sentience?

The key to developing organoids was the discovery of stem cells,

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Innovative Therapies, Care Equity Highlight 2022 ASCO Annual Meeting – Targeted Oncology

By daniellenierenberg

After a meeting like the 2022 ASCO Annual Meeting, one cannot help but be reinvigorated to continue advancing cancer care and feel optimistic about the future of oncology, says John M. Burke, MD.

After seeing all the amazing presentations at the American Society of Oncology (ASCO) Annual Meeting, I cannot help but reflect on how far our field has come over the course of my 20-year career.

In 2000, I moved from San Francisco, California, to New York, New York, to begin my fellowship at Memorial Sloan Kettering Cancer Center. My first rotation was on the inpatient myeloma, lymphoma, and autologous stem cell transplant service, where I encountered patients with myeloma and painful bone lesions causing fractures and spinal cord compressions. We treated patients with myeloma with chemotherapy and autologous stem cell transplant. Thalidomide (Thalomid) was starting to make a splash by showing strong efficacy in myeloma trials, and bortezomib (Velcade) emerged during those years, as well.

Nevertheless, the state of the art was exemplified by an article in the New England Journal of Medicine in 2003, describing the results of an Intergroupe Francophone du Mylome (IFM) trial. Myeloma patients were treated with vincristine, doxorubicin, and dexamethasone induction followed by single or double autologous stem cell transplant. The median event-free survival was 2 years and the median overall survival was 4 years, which seem grim by modern standards.

Fast forward about 20 years to the Plenary Session of the 2022 ASCO Annual Meeting, at which we saw the results of modern therapy in the DETERMINATION trial (NCT01208662). Patients treated with the modern standard regimen of lenalidomide (Revlimid), bortezomib, and dexamethasone followed by autologous stem cell transplant achieved a median progression-free survival of 5.5 years. In the IFM trial 20 years ago, approximately 50% of patients were alive at 4 years. In DETERMINATION, 85% of patients were alive at 4 years. Weve come a long way.

DETERMINATION represents only an infinitesimal fraction of the degree of innovation demonstrated at the ASCO meeting: an antibody-drug conjugate besting conventional chemotherapy in patients with low expression of the HER2 target in breast cancer; a KRAS inhibitor demonstrating marked activity in KRAS-mutated nonsmall cell lung cancer; a bispecific antibody redirecting T cells to suppress diffuse large B-cell lymphoma; an antibody-drug conjugate added to chemotherapy, extending survival in Hodgkin lymphoma compared with the decades-old standard-of-care regimen; and a checkpoint inhibitor rendering mismatch repairdeficient rectal cancer completely helpless.

After a meeting like this, one cannot help but be reinvigorated to continue advancing cancer care and feel optimistic about the future of oncology. We have a lot of progress to celebrateand a lot more to accomplish.

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Global Stem Cell Manufacturing Market Value Projected To Reach USD 21.71 Billion By 2029, Registering A CAGR Of 9.1% – Digital Journal

By daniellenierenberg

Global Stem Cell ManufacturingMarket Is Expected To Reach USD 21.71 Billion By 2029 At A CAGR Of 9.1 percent.

Maximize Market Research has published a report on theGlobal Stem Cell Manufacturing Marketthat provides a detailed analysis for the forecast period of 2022 to 2029.

Global Stem Cell ManufacturingMarket Scope:

The report provides comprehensive market insights for industry stakeholders, including an explanation of complicated market data in simple language, the industrys history and present situation, as well as expected market size and trends. The research investigates all industry categories, with an emphasis on key companies such as market leaders, followers, and new entrants. The paper includes a full PESTLE analysis for each country. A thorough picture of the competitive landscape of major competitors in theGlobal Stem Cell Manufacturingmarket by goods and services, revenue, financial situation, portfolio, growth plans, and geographical presence makes the study an investors guide.

Request Free Sample:@https://www.maximizemarketresearch.com/request-sample/73762

Global Stem Cell Manufacturing Market Overview:

Observing stem cells evolve into cells in bones, the circulatory system, nerve cells, and other organs of the body may help scientists understand how illnesses and disorders occur. Stem cells can be programmed to generate particular cells that can be utilized in humans to grow and mend tissues that have been damaged or harmed by sickness. Stem cell therapy may assist people with spinal cord injuries, metabolic disorders, Parkinsons disease, amyotrophic lateral sclerosis, Alzheimers disease, cardiovascular disorders, brain hemorrhage, burns, malignancy, and rheumatoid arthritis. Stem cells can be used to create new tissue for transplant and genetic engineering. Doctors are always learning more about stem cells and how they might be used in transplant and cellular therapies.

Global Stem Cell ManufacturingMarketDynamics:

Stem cells are crucial in illness treatment and specialized research initiatives such as customized therapy and genetic testing. As public and commercial stakeholders throughout the world become more aware of stem cells therapeutic potential and the scarcity of therapeutic approaches for rare illnesses, they are increasingly focusing on the development of stem cell-based technology.

Specialized procedures are required for stem cell separation, refinement, and storage (such as expansion, differentiation, cell culture media preparation, and cryopreservation). Additionally, the production scale-up of stem cell lines and associated items is frequently accompanied by major technological challenges that impede the whole production process and result in large operational expenses. As a result, stem cell products are frequently more expensive than pharmaceutical medications and biopharmaceuticals.

Additionally, the growing popularity of tailored medications is driving the market growth. Scientists are researching novel procurement strategies that can be used to manufacture tailored medications. For example, iPSC treatments are created by taking a little amount of a patients plasma or skin cells and reprogramming them to make new cells and tissue for transplant. As a result, future tailored treatments can be produced using these cells.

Global Stem Cell ManufacturingMarketRegional Insights:

North America (particularly the United States) held the largest market share in 2021, owing to factors such as the availability of significant contenders active in creating stem cell treatments, enhanced medical facilities, significant R&D financial backing available, and favorable initiatives from healthcare organizations, as well as robust reimbursement. Because of government initiatives and serious scientific activity in the country, the United States leads the continentsGlobal Stem Cell Manufacturingmarket.

Healthcare organizations are promoting cellular therapies for rising ailments. Due to higher advancement of stem cell-based treatments, federal actions for creating regenerative medications, the creation of multiple stem cell banks, and the continents increasing clinical studies for genetic manipulation and medical technology, the APACGlobal Stem Cell Manufacturingmarket is expected to grow at the fastest rate during the forecast period.

Global Stem Cell ManufacturingMarketSegmentation:

By Product:

By Application:

By Technology:

By Therapy:

Global Stem Cell ManufacturingMarket Key Competitors:

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Maximize Market Research is a multifaceted market research and consulting company with professionals from several industries. Some of the industries we cover include medical devices, pharmaceutical manufacturers, science and engineering, electronic components, industrial equipment, technology and communication, cars and automobiles, chemical products and substances, general merchandise, beverages, personal care, and automated systems. To mention a few, we provide market-verified industry estimations, technical trend analysis, crucial market research, strategic advice, competition analysis, production and demand analysis, and client impact studies.

Contact Maximize Market Research:

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Stem Cell Therapy Market Is Expected To Reach USD 455.61 Billion By 2027 At A CAGR Of 16 percent By Forecast 2027 Says Maximize Market Research (MMR)…

By daniellenierenberg

Stem Cell Therapy Market Is Expected To Reach USD455.61 Billion By 2027 At A CAGR Of 16 percent.

Maximize Market Research has published a report on theStem Cell Therapy Marketthat provides a detailed analysis for the forecast period of 2022 to 2027.

Stem Cell Therapy Market Scope:

The report provides comprehensive market insights for industry stakeholders, including an explanation of complicated market data in simple language, the industrys history and present situation, as well as expected market size and trends. The research investigates all industry categories, with an emphasis on key companies such as market leaders, followers, and new entrants. The paper includes a full PESTLE analysis for each country. A thorough picture of the competitive landscape of major competitors in the Stem Cell Therapy market by goods and services, revenue, financial situation, portfolio, growth plans, and geographical presence makes the study an investors guide.

To Get A Copy Of The Sample of the Stem Cell Therapy Market, Click Here:https://www.maximizemarketresearch.com/request-sample/522

Stem Cell Therapy Market Overview:

Stem cells, which are the most important in the body, exist in both humans and animals. Stem cells, which may multiply and grow into almost any cell type in the body, are employed in surgery and medicine. There are two types of stem cells: adult stem cells and embryonic stem cells. Embryonic stem cells are stem cells derived from human embryos (ESCs). They are pluripotent, which means they can develop into practically any type of cell in the body. Regenerative medicine or cornerstone treatment are other terms for stem cell therapy. Regenerative medicines can restore cells and replace those that have been damaged or killed.

Mesenchymal stem cells may penetrate and integrate into different organs, heal cardiovascular, lung, and spinal cord injuries, and ameliorate the condition of autoimmune illnesses, liver disorders, and bone and cartilage diseases. Stem cells are an effective therapy option for infections induced by inflammation, immune system failure, or tissue degradation.

Stem Cell Therapy MarketDynamics:

The use of stem cells in regenerative medicine, notably in dermatology, is likely to drive significant growth in the global Stem Cell Therapy Market during the forecasted period. Additionally, increased oncology use, as a result of a large number of pipeline medications under development for the treatment of tumors or malignancies, would move the market ahead. The stem cell business is expected to flourish in the future as the number of regenerative medicine clinics increases. Moreover, the rising prevalence of chronic diseases has assisted the growth of the stem cell treatment sector.

Long work hours, a lack of physical activity, and unhealthy eating and drinking habits all lead to the development of chronic diseases and need stem cell therapy. Moreover, the growing death rate from chronic diseases throughout the world is expected to propel the worldwide Stem Cell Therapy Market ahead. Additionally, the growing popularity of personalized pharmaceuticals is driving the worldwide Stem Cell Therapy Market. Researchers have identified new procurement strategies that can be used to generate personalized pharmaceuticals.

Because stem cells are generated by killing human embryos, they raise several ethical concerns. Human embryos are recognized as potential life, and eliminating them, even if they can save a human life, is considered immoral. Concerns about using embryonic stem cells to develop stem cell therapies are restricting the global market growth.

To get more Report Details, Click here:https://www.maximizemarketresearch.com/market-report/stem-cell-therapy-market/522/

Stem Cell Therapy MarketRegional Insights:

The market for stem cell treatment was dominated by North America, Asia Pacific, and Europe. This geographical segments significant share of the stem cell therapy market can be attributed to increased public-private financing and research grants for producing safe and effective stem cell treatment products, as well as the growing number of clinical trials, as well as North Americas major share of the stem cell therapy market with increased sales of stem cell therapy.

Stem Cell Therapy MarketSegmentation:

By Treatment:

By Therapeutic Application:

By Cell Source:

By End users:

Stem Cell Therapy Market Key Competitors:

About Maximize Market Research:

Maximize Market Research is a multifaceted market research and consulting company with professionals from several industries. Some of the industries we cover include medical devices, pharmaceutical manufacturers, science and engineering, electronic components, industrial equipment, technology and communication, cars and automobiles, chemical products and substances, general merchandise, beverages, personal care, and automated systems. To mention a few, we provide market-verified industry estimations, technical trend analysis, crucial market research, strategic advice, competition analysis, production and demand analysis, and client impact studies.

Contact Maximize Market Research:

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+91 96071 95908, +91 9607365656

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This startup wants you to have a personal stem cell stash – Freethink

By daniellenierenberg

Salvatore Viscomi always wanted to be involved in a science fiction project and he found one.

Viscomi is the chief medical officer of GoodCell, a Massachusetts-based startup where people can bank their own white blood cells with a simple blood draw. Labs can then tweak those cells to become what are called induced pluripotent stem cells (iPSCs).

Already sounds like the premise of a novella, right? Well those iPSCs are where things get really fantastical: those cells can become any type of cell in the human body.

There lies in the therapy, Viscomi, who initially was involved in GoodCell as an investor and advisor before becoming CMO, tells Freethink.

Specific white blood cells can be turned into induced pluripotent stem cells (iPSCs) cells which can become any type of cell in the body.

The new stem cells could be made into pancreatic cells to treat diabetes, blood cells to replace those ravaged by leukemia, or neurons to treat brain disorders, according to UCLAs Broad Stem Cell Research Center.

While the white blood cells that can become iPSCs called peripheral blood mononuclear cells, or PBMCs can come from donors or the patients own bone marrow, both have drawbacks.

Donor cells, like any transplant, may require immunosuppression to prevent rejection, which can leave recipients vulnerable to infections. (A particularly acute issue now, with the invisible war with pathogens going hot all around us.)

And extracting cells from the bone marrow involves anesthesia and long needles nothing near as simple as a blood draw.

Now, we dont have to make that difficult decision, Viscomi says.

Finding your potential: Human iPSCs were first created in Japan in 2007. Kyoto University researcher Shinya Yamanaka received a Nobel Prize for his work with University of Cambridges John B. Gurdon, which discovered how to turn adult cells back into stem cells.

According to a recent article by Yamanaka, as of September 2020, clinical trials of iPSC therapies are currently in the works for Parkinsons, heart failure, spinal cord injury, macular degeneration a very common vision disorder in those over 50 and cancer immunotherapy, among sundry others.

There are, however, challenges to be overcome before iPSCs can find their way to patients.

As of September 2020, clinical trials of iPSC therapies are currently in the works for Parkinsons, heart failure, and spinal cord injury, among sundry others.

There is the potential that the stem cells will proliferate beyond what we want them to, leading to tumors. The body may reject even its own stem cells, with conflicting experiments in mice finding possible evidence of rejection, possibly due to abnormal expression of genes in the new cells.

Theres another challenge as well: the ability to crank out enough iPSCs needed for therapies to be practical.

Despite all of that, however, pluripotent stem cells like iPSCs provide unprecedented opportunities for cell therapies against intractable diseases and injuries, Yamanaka wrote.

Banking on yourself: Banking your cells ahead of time can help ensure the cells are as young and healthy as possible, as they do deteriorate with age, Viscomi says.

To bank your own cells, GoodCell requires a 40cc blood draw, the minimum amount required for producing enough iPSCs. Customers receive a draw kit from GoodCell, which they can take to a lab their current partner is Quest or have a phlebotomist do it at home.

That sample is sent to GoodCells laboratory, where the white blood cells that can become iPSCs are isolated, extracted, and slowly frozen (to avoid damaging them).

Theyre stored at really super cold temperatures, Viscomi says. Its a slow freezing process, really kind of a proprietary way of storing them in the best way we know today in terms of keeping them viable.

GoodCell stores the white blood cells for potential use in future stem cell therapies.

If members request it, the company can also run genetic tests for heritable conditions on the material in the sample, which they will test for actionable conditions only, Viscomi says. Tests for non-heritable genetic changes are currently being developed.

Were taking a really comprehensive look at personalized medicine, Viscomi says.

Because of the potentially sensitive nature of the samples, all uses of the patients data must be opted in to, Viscomi says, while the stem cells banks themselves are hardened, bunkers outfitted with cameras, backup power supplies, and designed to resist natural disasters. The privacy systems were tested across a two year beta period.

GoodCell officially began offering personal stem cell banking services on June 6.

Wed love to hear from you! If you have a comment about this article or if you have a tip for a future Freethink story, please email us at tips@freethink.com.

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Parents of 12-Year-Old Boy Praying for a Miracle, Appealing UK Judge’s Decision to Remove Life Support – CBN.com

By daniellenierenberg

The parents of a 12-year-old boy who's on life support are appealing the decision of the UK Royal Courts of Justice to remove his oxygen and other life-sustaining treatment. They're taking their case to a Court of Appeal hearing in London on Wednesday.

As CBN News reported earlier this month, Family Division of the High Court Judge Emma Arbuthnot ruled "on the balance of probabilities" Archie Battersbee had already died after doctors told the court "it was highly likely" he was "brain stem dead."

Archie's mother and father, Holly Dance and Paul Battersbee are trying to give their son every chance at life after he was found unconscious on April 7 with a cord around his neck. He reportedly had participated in what is believed to be an online blackout challenge, according to watchdog Christian Concern.

The boy has remained on life support at the Royal London Hospital and has not regained consciousness.

Judge Arbuthnot ordered, "Medical professionals at the Royal London Hospital (1) to cease to ventilate mechanically Archie Battersbee; (2) to extubate Archie Battersbee; (3) to cease the administration of medication to Archie Battersbee, and (4) not to attempt any cardio or pulmonary resuscitation on Archie Battersbee when cardiac output ceases or respiratory effort ceases."

"The steps I have set out above are lawful," the judge contended. But she also gave Archie's mother and father, Holly Dance and Paul Battersbee permission to appeal her ruling.

Arbuthnot said there was a "compelling reason" why appeal judges should consider the case, according to ITV News.

According to Christian Concern, this is believed to be the first time that someone in the UK has been declared 'likely' to be dead based on an MRI test.

At a High Court hearing about Archie's case on June 20, Christian Legal Centre attorney Edward Devereux QC argued that evidence should instead show 'beyond reasonable doubt', as in criminal proceedings, that Archie is dead, rather than using a balance of probabilities test.

Archie's parents have been fighting a legal battle to give their son more time and to allow him to have more medical tests to assess whether his condition improves before making the decision about withdrawing his life support.

In a statement, Archie's mother, Hollie, and sister-in-law, Ella Carter, asked: "If Archie can be pronounced dead via an MRI, which is outside the bounds of the law, then what's going to be next?"

They also thanked everyone for the support the family has received from around the world.

"Archie's words, if he was sitting next to me right now, would be 'it melts my heart' and I'll use those words now, because everyone's support does melt my heart. So, thank you and please continue to support us in this fight," the statement said.

Proof of Life?

Archie's parents say a video of him gripping his mother's fingers is proof that he's still alive and his brain is functioning.

But his doctors believe there's no hope for the boy to recover since they believe his brain stem is dead. Scans reportedly show blood is not flowing to the area, according to Sky News. The stem lies at the base of the brain above the spinal cord. It is responsible for regulating most of the body's automatic functions essential for life. Doctors previously said Archie's stem is 50% damaged and that 10% to 20% of the stem is in necrosis where cells have died and/or are decaying.

***Please sign up forCBN Newslettersand download theCBN News appto ensure you keep receiving the latest news from a distinctly Christian perspective.***

Lawyers for the Barts Health NHS Trust said that doctors have repeatedly recreated the moment of the boy holding a clinician's hand, but the hospital workers said it was just "friction" not a grip, which the doctors say is consistent with muscle stiffness.

Eminent Pediatric Neurologist Testified About Cases of Persons Diagnosed as 'Brain Dead' Who Later Recovered

Dr. D. Alan Shewmon, M.D., professor emeritus of Neurology and Pediatrics at the University of California, gave expert testimony about numerous documented cases where persons diagnosed as 'brain dead' subsequently recovered.

When asked whether there was sufficient evidence for a reliable diagnosis of death in Archie's case, Shewmon replied, "Absolutely not."

An online petition to the hospital's chief executive officer has been created to ask that legal action be withdrawn in Archie's case. So far, more than 89,000 people have signed it.

A GoFundMe page has also been set up on the boy's behalf. So far, the account has raised 29,042 GBP (or approximately $35,479 in U.S. dollars).

Archie's mom told Christian Concern earlier this month that the judge's ruling that he's "likely" to be dead is not good enough.

"Basing this judgment on an MRI test and that he is 'likely' to be dead, is not good enough. This is believed to be the first time that someone has been declared 'likely' to be dead based on an MRI test," she explained.

"The medical expert opinion presented in Court was clear in that the whole concept of 'brain death' is now discredited, and in any event, Archie cannot be reliably diagnosed as brain-dead," Dance continued.

She reiterated that she does not believe her son has been given enough time to heal.

"I do not believe Archie has been given enough time. From the beginning, I have always thought 'why the rush?' His heart is still beating, he has gripped my hand, and as his mother, I know he is still in there," she noted.

"Until it's God's way, I won't accept he should go. I know of miracles when people have come back from being brain dead," Dance said.

Andrea Williams, chief executive of the Christian Legal Centre, said in a statement that Archie's case has raised "significant moral, legal and medical questions as to when a person is dead."

"Archie's parents believe that the time and manner of his death should be determined by God and claim a right to pray for a miracle until and unless that happens. That belief must be respected. The ideology of 'dignity in death', meaning a planned time of death as fixed and carried out by the doctors, should not be brutally imposed on families who do not believe in it," Williams said.

"We will continue to stand with the family as they appeal the ruling and continue to pray for a miracle," she concluded.

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The end of Roe v. Wade affects more than just abortion – Vox.com

By daniellenierenberg

The end of Roe v. Wade will not only jeopardize access to abortion in many states, it could have wide-ranging and unpredictable consequences for medical care, including fertility treatment, contraception, and cancer care.

This post-Roe world will be, in many ways, a new era for medical care in the United States, one that could transform medical services for conditions that range far beyond pregnancy, either by making them illegal or by putting their legality in question.

The consequences are unpredictable. Michelle Banker, director of reproductive rights and health litigation at the National Womens Law Center, told me in an interview before Fridays decision that the effect on other types of health care will depend upon the answers to open and untested questions in US courts. Some of it will rest on how judges will interpret new state abortion bans. States could also be emboldened by the Supreme Courts ruling to pass new legislation that restricts other medical services.

History would suggest places that outlaw abortion tend to have less access to other reproductive care as well. In Ireland, which only recently legalized abortion, there is still less access to in vitro fertilization and certain contraceptives than in the rest of Europe, even after abortion became legal. In the US, a health system that is already fractured will become even more so, limiting access to medical care particularly for marginalized patients. Whether you can get certain health care services may be predicated on where you live (or whether you can afford to travel).

The breadth of the potential health care consequences is so broad, Banker said. The first place to start is this is going to result in the death of pregnant people.

The United States has the highest maternal mortality rates among wealthy nations; Black Americans have a significantly higher mortality rate than anywhere else in the developed world. The risk of death from carrying a pregnancy to term is much higher than the risk of death from undergoing an abortion. One estimate puts the number of forced birth in the first year after Roe is overturned at 75,000; the maternal mortality rate in the US is about 1 in 10,000.

The impact the end of Roe could have on pregnancy care could reach much further. As the Atlantics Sarah Zhang wrote, pregnant women undergo genetic and other tests throughout their pregnancy, meant to assess the health of the fetus and identify any anomalies that could be fatal or life-altering. In some cases, parents who learn about these anomalies choose abortion. But that may no longer be so simple if abortion is now outlawed or severely limited. Decisions about whether to get genetic testing and when could be affected.

By the same token, most abortion bans would carve out exceptions if the health of the mother were in jeopardy. But whether a complication represents a life-threatening risk to the mothers health is in part a judgment call on the part of her doctor and the possibility of legal consequences could make the cost of mistakes much higher.

At the very least, there may well be a chilling effect due to providers and patients uncertainty as to whether treatment could expose them to civil or criminal liability, Banker said.

Fetal personhood laws that convey constitutional protections to unborn fetuses would further limit a pregnant persons choices in medical care. Several states have attempted to pass such a law, but they have thus far been held up by the courts. This new post-Roe jurisprudence could embolden those states and others to put such measures into place. Law enforcement or private citizens, depending on the state law, could bring complaints. The recently signed Texas law, for example, deputizes private citizens by creating a financial incentive for them to take civil action against people who seek or provide abortions.

Or, in a less extreme example, what happens if a pregnant person is also receiving cancer treatment or taking mental health medication that could affect the health of their fetus? If they stop receiving that medical care, their health could be in danger. But if they continue to receive it, the fetus could be affected. What are they and their doctor supposed to do?

The laws that criminalize abortion are going to impact medical decision-making, and thats terrifying, Banker said.

Supporters of abortion rights fear that, unchained by the Supreme Court, states could push deeper and deeper into the lives of pregnant women and the decisions they make about how to conduct themselves.

People have been arrested for substance use during pregnancy, based on reasoning that they are harming the growth of the pregnancy. Tennessee passed the first law permitting the prosecution of pregnant women who use drugs. That alone is objectionable to people who oppose a criminalized approach to substance use. But they also worry that such laws are just the tip of the iceberg in a post-Roe reality. Could a pregnant woman be charged with a crime if she drinks a glass of wine? Or if she goes on a hiking trip that a complainant thinks would imperil the health of her fetus?

These questions will be answered by the specifics of state laws and the discretion of prosecutors in different places. But they are questions that were unfathomable just a few months ago.

How far down this path could states go? said Elizabeth Nash, who tracks state policy at the Guttmacher Institute, in an interview before Fridays Supreme Court ruling. That might sound a bit far-fetched to people but we have seen states take drastic actions in relation for some pregnant people.

Beyond medical care during pregnancy, the end of Roe could usher in a wave of new restrictions on access to contraception and fertility treatment.

The right to contraception is currently upheld by two previous Supreme Court decisions: Griswold v. Connecticut enshrined the right for married people and Eisenstadt v. Baird did the same for unmarried people.

But the current Court is clearly not bound by those precedents if they are willing to overturn Roe v. Wade. And some prominent Republicans, such as Sen. Marsha Blackburn (R-TN), have referred to those prior court decisions as constitutionally unsound in the days since the Alito draft leaked.

That puts case law in jeopardy because it relies on this idea that rights not specifically named in the Constitution are only entitled to special protection if they are deeply rooted in the nations traditions, Banker said.

Other experts I spoke to agreed. The stage is very much set for state legislators to ban contraception if they want to, Sean Tipton, who works on policy issues at the American Society for Reproductive Medicine, told me before the Supreme Court ruled.

Would state legislators want to ban condoms or even birth control pills? Maybe not. But new laws or even state abortion bans could target other kinds of birth control.

Many of these states want to define the beginning of life as early as possible in the biological process. Oklahoma, for one, passed a law that recognized an unborn childs life as beginning at fertilization. Other states describe the moment of conception. But, as Tipton pointed out, the early stages of pregnancy are, medically speaking, a process. There is not a single moment of conception.

But if states define life in such a way, then contraceptives that could prevent a fertilized egg from becoming implanted could be under threat.

IUDs and the morning-after pill would be threatened under such a legal regime. In the vast majority of cases, IUDs work by preventing fertilization: the sperm and the egg never meet in the first place. But they also might prevent implantation under certain circumstances. There is also some controversy about whether Plan B, the morning-after pill, prevents fertilization in the first place or whether it blocks the implantation of a fertilized egg. The latter could arguably be illegal in states that recognize life at fertilization. Lawmakers in Idaho, for example, announced hearings on whether to ban emergency contraceptives and possibly IUDs before the Supreme Court had even issued its final ruling.

Then there are fertility treatments particularly in vitro fertilization that depend on fostering a larger number of eggs but typically only use a small number of them. If an embryo is conferred the same rights as a toddler, are those procedures suddenly illegal?

As Tipton put it to me, what if a doctor puts 199 embryos in a freezer for IVF treatment, and 198 of them come out of the freezer okay? Does that mean a homicide has been committed? he said.

Experts imagine other possible restrictions on procedures like IVF, particularly in states that define life as beginning at conception or fertilization. That alone could put IVF in legal jeopardy. States could also institute new restrictions on those procedures, now that the right to privacy has been redefined. Maybe the number of embryos could be limited. Maybe state legislators restrict which people are allowed to avail themselves of those services to only straight married couples, for example.

And while there is a tension between ostensibly pro-life politicians restricting access to fertility care, there is an expectation that anti-abortion advocates would be willing to let these medical services be collateral damage in order to achieve the goal of outlawing abortion.

Most right-to-life proponents are not interested in doing anything to hurt fertility patients, Tipton said. But theyre very willing to throw those patients under the bus to end abortion.

The new jurisprudence could also affect access to health care that has nothing to do with pregnancy or reproduction, experts say.

Medical care for people undergoing a gender transition would be one possible casualty. The decision in particular puts gender-affirming care in its crosshairs, Banker said.

In the opinion, Alito cited a 1974 decision, Geduldig v. Aiello, that takes what Banker calls a very narrow and cramped view of what constitutes sex discrimination. For Alitos purposes, that narrow view of sex discrimination supports the argument that banning abortion would not constitute discrimination against pregnant people on the basis of sex.

But Banker says the same logic could be applied to gender-affirming health care such as surgery or hormonal treatments. If the Supreme Courts definition of sex discrimination is now much narrower than it used to be, then opponents of those services could argue that denying a person gender-affirming medical care is not actually discriminatory.

Those arguments are easily refuted under modern precedent, Banker told me. But the drafts language and citation to Geduldig raises concerns that we may see those arguments gain more traction.

Old battles over medical research or treatment could also resurface, Tipton said. Modern science has developed treatments for spinal cord injuries, myelofibrosis, and even certain cancers by relying on stem cells. More treatments are in clinical trials right now. But their prospects could be compromised if access to those materials is limited. Some stem cells are collected from adult body tissue, but others come from embryos.

Much of this will depend on how aggressive anti-abortion advocates decide to be, and on the success of abortion rights advocates in mounting a political and legal response to a ruling overturning Roe.

But it will undoubtedly be a new era for health care in the United States, with potentially devastating consequences for patients with a wide array of medical needs.

Originally posted here:
The end of Roe v. Wade affects more than just abortion - Vox.com

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Horizon Therapeutics plc Submits Regulatory Filing for UPLIZNA (inebilizumab) in Brazil – Business Wire

By daniellenierenberg

DUBLIN--(BUSINESS WIRE)--Horizon Therapeutics plc (Nasdaq: HZNP) today announced that it has submitted a regulatory filing to the Brazil National Health Surveillance Agency (ANVISA) for UPLIZNA for the treatment of adult patients with anti-aquaporin-4 immunoglobulin G seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD).

This regulatory submission is an important milestone as we continue to expand our commitment to NMOSD patients around the world, said Vikram Karnani, executive vice president and president, international operations, Horizon. NMOSD is a devastating disease with unpredictable attacks, which can result in potential loss of vision and motor function. We are hopeful that we can bring a potential new treatment option to the estimated ten thousand people living with NMOSD in Brazil.

In the N-MOmentum Phase 3 clinical trial, the largest NMOSD trial to date, UPLIZNA demonstrated a significant reduction in the risk of an NMOSD attack with only two infusions per year, following the initial two loading doses. Additionally, 89% of patients in the AQP4-IgG+ group remained attack-free during the six-month period post-treatment and 83% of patients on treatment remained attack-free for at least four years.1,2

UPLIZNA was approved by the U.S. Food and Drug Administration (FDA) in June 2020, by the Japanese Ministry of Health, Labor and Welfare in March 2021 and by the European Commission (EC) in April 2022. Mitsubishi Tanabe Pharma Corporation has the rights to develop and commercialize UPLIZNA in Japan, Thailand, South Korea, Indonesia, Vietnam, Malaysia, the Philippines, Singapore and Taiwan. Hansoh Pharmaceutical Group Company Limited, another strategic partner to Horizon, has also recently received manufacturing and marketing approval from the National Medical Products Administration of the Peoples Republic of China for UPLIZNA.

About Neuromyelitis Optica Spectrum Disorder (NMOSD)

NMOSD is a unifying term for neuromyelitis optica (NMO) and related syndromes. NMOSD is a rare, severe, relapsing, neuroinflammatory autoimmune disease that attacks the optic nerve, spinal cord, brain and brain stem.3-4 Approximately 80% of all patients with NMOSD test positive for anti-AQP4 antibodies.5 AQP4-IgG binds primarily to astrocytes in the central nervous system and triggers an escalating immune response that results in lesion formation and astrocyte death.6

Anti-AQP4 autoantibodies are produced by plasmablasts and plasma cells. These B-cell populations are central to NMOSD disease pathogenesis, and a large proportion of these cells express CD19.7 Depletion of these CD19 B cells is thought to remove an important contributor to inflammation, lesion formation and astrocyte damage. Clinically, this damage presents as an NMOSD attack, which can involve the optic nerve, spinal cord and brain.6-8 Loss of vision, paralysis, loss of sensation, bladder and bowel dysfunction, nerve pain and respiratory failure can all be manifestations of the disease.9 Each NMOSD attack can lead to further cumulative damage and disability.10,11 NMOSD occurs more commonly in women and may be more common in individuals of African and Asian descent.12,13

About UPLIZNA (inebilizumab-cdon)

INDICATION

UPLIZNA is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

IMPORTANT SAFETY INFORMATION

UPLIZNA is contraindicated in patients with:

WARNINGS AND PRECAUTIONS

Infusion Reactions: UPLIZNA can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash or other symptoms. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions. Administer pre-medication with a corticosteroid, an antihistamine and an anti-pyretic.

Infections: The most common infections reported by UPLIZNA-treated patients in the randomized and open-label periods included urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%) and influenza (7%). Delay UPLIZNA administration in patients with an active infection until the infection is resolved.

Increased immunosuppressive effects are possible if combining UPLIZNA with another immunosuppressive therapy.

The risk of Hepatitis B Virus (HBV) reactivation has been observed with other B-cell-depleting antibodies. Perform HBV screening in all patients before initiation of treatment with UPLIZNA. Do not administer to patients with active hepatitis.

Although no confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) were identified in UPLIZNA clinical trials, JC virus infection resulting in PML has been observed in patients treated with other B-cell-depleting antibodies and other therapies that affect immune competence. At the first sign or symptom suggestive of PML, withhold UPLIZNA and perform an appropriate diagnostic evaluation.

Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNA.

Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation, until B-cell repletion.

Reduction in Immunoglobulins: There may be a progressive and prolonged hypogammaglobulinemia or decline in the levels of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued UPLIZNA treatment. Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with UPLIZNA until B-cell repletion especially in patients with opportunistic or recurrent infections.

Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping UPLIZNA.

Adverse Reactions: The most common adverse reactions (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infection and arthralgia.

For additional information on UPLIZNA, please see the Full Prescribing Information at http://www.UPLIZNA.com.

About Horizon

Horizon is a global biotechnology company focused on the discovery, development and commercialization of medicines that address critical needs for people impacted by rare, autoimmune and severe inflammatory diseases. Our pipeline is purposeful: We apply scientific expertise and courage to bring clinically meaningful therapies to patients. We believe science and compassion must work together to transform lives. For more information on how we go to incredible lengths to impact lives, visit http://www.horizontherapeutics.com and follow us on Twitter, LinkedIn, Instagram and Facebook.

Forward-Looking Statements

This press release contains forward-looking statements, including, but not limited to, statements related to potential regulatory approval of UPLIZNA in Brazil and the potential benefits of UPLIZNA to patients in Brazil. These forward-looking statements are based on management expectations and assumptions as of the date of this press release, and actual results may differ materially from those in these forward-looking statements as a result of various factors. These factors include the risk that UPLIZNA does not receive regulatory approval in Brazil, whether, if regulatory approval is received, UPLIZNA will be successfully commercialized in Brazil, and those risks detailed from time-to-time under the caption "Risk Factors" and elsewhere in Horizons filings and reports with the SEC. Horizon undertakes no duty or obligation to update any forward-looking statements contained in this press release as a result of new information.

References

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Horizon Therapeutics plc Submits Regulatory Filing for UPLIZNA (inebilizumab) in Brazil - Business Wire

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Effect of Electrical Stimulation on Spinal Cord Injury: In Vitro and In Vivo Analysis – Newswise

By daniellenierenberg

Abstract: Electrical stimulation influences neural stem cell neurogenesis. We analyzed the effects of electrical stimulation on neurogenesis in rodent spinal cord-derived neural stem cells (SC-NSCs) in vitro and in vivo and evaluated functional recovery and neural circuitry improvements with electrical stimulation using a rodent spinal cord injury (SCI) model. Rats (20 rats/group) were assigned to a sham (Group 1), SCI only (Group 2), SCI + electrode implant without stimulation (Group 3), and SCI + electrode with stimulation (Group 4) groups to count total SC-NSCs and differentiated neurons and evaluate morphological changes in differentiated neurons. Further, the Basso, Beattie, and Bresnahan scores were analyzed, and the motor and somatosensory evoked potentials in all rats were monitored. In vitro, biphasic electrical currents increased SC-NSC proliferation and neuronal differentiation and caused qualitative morphological changes in differentiated neurons. Electrical stimulation promoted SC-NSC proliferation and neuronal differentiation and improved functional outcomes and neural circuitry in SCI models. Increased Wnt3, Wnt7, and -catenin protein levels were also observed after electrical stimulation. In conclusion, our study proved the beneficial effects of electrical stimulation on SCI. We believe that Wnt/-catenin pathway activation may be associated with this relationship between electrical stimulation and neuronal regeneration after SCI.

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Effect of Electrical Stimulation on Spinal Cord Injury: In Vitro and In Vivo Analysis - Newswise

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