Multiple Myeloma Experts, Patients, Advocates and Caregivers Team Up to Hike Through Patagonia – BioSpace
By daniellenierenberg
Since MM4MM began with its first climb in 2016, the program has raised over $2.7 million. All the funds raised go directly to the MMRF to accelerate new treatment options for patients with multiple myeloma.
As a patient founded organization, the MMRF stands together with those who are battling multiple myeloma patients, families, physicians, researchers, and our pharmaceutical partners. This team represents a microcosm of that myeloma community and demonstrates that together, we can collaborate with ever increasing momentum towards a cure, said Paul Giusti, CEO of the Multiple Myeloma Research Foundation. We are thrilled to enter the fifth year of this inspiring program and to have Celgene join us in this effort to raise awareness and critical funds to continue our mission.
The MM4MM team will include four patients living with multiple myeloma:
We are so honored to be a part of yet another hike with the MMRF and Celgene, said Mike Hennessy Jr., president and CEO of MJH Life Sciences, parent company of CURE magazine. This initiative organized by Moving Mountains for Multiple Myeloma not only raises awareness and research funding for multiple myeloma but has brought together the myeloma community to take action and fight for a cure for myeloma patients.
The team will embark on a five-day trek of a lifetime through Patagonia and take on the rewarding and beautiful landscape that includes glaciers, deep valleys and challenging peaks. During this trek, the team will travel through El Chaltn and acclimatize while they experience the mighty range of peaks dominated by Monte Fitz Roy, an 11,020-foot tower with a sheer face of more than 6,000 feet. Next, the team will reach Lago San Martin, where they will traverse the terrain in daily treks, exploring a 10-mile peninsula, climbing to a condor rookery and reaching remote Andean lakes.
Celgene, Cure and the MMRF share an unwavering commitment to improving the lives of patients with multiple myeloma and we are very proud to continue our role in the Moving Mountains for Multiple Myeloma initiative, said Chad Saward, senior director, patient advocacy at Celgene Corp. We are amazed and inspired by all who are participating in this unique awareness program.
To learn more about MM4MM and to donate to multiple myeloma research, click here.
About Moving Mountains for Multiple Myeloma
Moving Mountains for Multiple Myeloma (MM4MM) is a collaboration between CURE Media Group and the Multiple Myeloma Research Foundation (MMRF) to raise awareness and funds for myeloma research. This year, Celgene Corporation and GSK join the effort as sponsors. In addition to Patagonia, the program also led hikes up Mt. Washington and through Iceland in 2019. To date, MM4MM has raised over $2.7 million for myeloma research and included 51 patients with multiple myeloma on 7 climbs. Funds raised go directly to research, supporting the MMRF mission. For more information, visit https://www.themmrf.org/events/.
About Multiple Myeloma
Multiple myeloma (MM) is a cancer of the plasma cell. It is the second most common blood cancer. An estimated 32,110 adults (18,130 men and 13,980 women) in the United States will be diagnosed with MM in 2019 and an estimated 12,960 people are predicted to die from the disease. The five-year survival rate for MM is approximately 50.7%, versus 31% in 1999.
About the Multiple Myeloma Research Foundation
A pioneer in precision medicine, the Multiple Myeloma Research Foundation (MMRF) seeks to find a cure for all multiple myeloma patients by relentlessly pursuing innovations that accelerate the development of precision treatments for cancer. Founded in 1998 by Kathy Giusti, a multiple myeloma patient, and her twin sister Karen Andrews as a 501(c)(3) nonprofit organization, the MMRF has created the business model around cancerfrom data to analytics to the clinic. The MMRF identifies barriers and then finds the solutions to overcome them, bringing in the best partners and aligning incentives in the industry to drive better outcomes for patients. Since its inception, the organization has collected thousands of samples and tissues, opened nearly 100 trials, helped bring 10 FDA-approved therapies to market, and built CoMMpass, the single largest genomic dataset for any cancer. Today, the MMRF is building on its legacy in genomics and is expanding into immune-oncology, as the combination of these two fields will be critical to making precision medicine possible for all patients. The MMRF has raised nearly $500 million and directs nearly 90% of the total funds to research and related programs. To learn more, visit http://www.themmrf.org.
About CURE Media Group
CURE Media Group is the leading resource for cancer updates, research and education. It combines a full suite of media products, including its industry-leading website, CUREtoday.com; innovative video programs, such as CURE Connections; a series of widely attended live events; and CURE magazine, which reaches over 1 million readers, as well as the dynamic website for oncology nurses, OncNursingNews.com, and its companion publication, Oncology Nursing News. CURE Media Group is a brand of MJH Life Sciences, the largest privately held, independent, full-service medical media company in the U.S. dedicated to delivering trusted health care news across multiple channels.
View source version on businesswire.com: https://www.businesswire.com/news/home/20191022006008/en/
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Multiple Myeloma Experts, Patients, Advocates and Caregivers Team Up to Hike Through Patagonia - BioSpace
Turmeric: Uses and benefits of the spice that you must know – Republic World – Republic World
By daniellenierenberg
Turmeric has numerous uses when it comes to health benefits. They are being used in Indian households for a long time.These include several health benefits and medicinal uses. Turmeric is one of the most powerful spices. It has a unique taste with a mix of citrusy bitterness. It is also associated with Ayurvedic practices.
Also read:Indian Food: What Are The Uses Of Turmeric In Indian Dishes?
Turmeric also has some benefits to enhance your beauty. Its anti-inflammatory properties help in removing dead skin cells. It can also be used to wash your fash or apply once in a while. There are several benefits you can receive from turmeric. These are some of the imperative ones.
Also read:Basil Benefits: Top Benefits Of Basil For Your Skin
The anti-inflammatory properties that are found in turmeric are used to soothe osteoarthritis and rheumatoid arthritis. These collectively work in your favour. The antioxidant destroys the free radicals in the body that damage the cells. These can help alleviate and relax your mild joint pains. It cannot be used as a substitute for medication.
There is a compound in turmeric that has not been studied as much as the other compounds like curcumin - aromatic turmerone or ar-turmerone. This compound has reportedly been repairing brain stem cells. It also helps in the recovery from neurodegenerative diseases like stroke and Alzheimer's.
A substance in turmeric Lipopolysaccharide has anti-bacterial, anti-fungal, and anti-viral agents. This also helps to stimulate the immune system. Make sure you consume only a teaspoon in warm water.
Also read:Jackfruit: Delicious Recipes To Make With The Diabetic Friendly Fruit
The anti-inflammatory and antioxidant properties of curcumin help to reduce the onset of Type 2 diabetes. It helps to moderate insulin levels and boosts the effect of medications that treat diabetes. But always remember not to use it as a source of medication.
Turmeric increases the production of vital enzymes that detoxify our blood in the liver by breaking down and reducing the toxins. It also helps with the circulation of blood. Overall, it is known to improve liver health.
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Turmeric: Uses and benefits of the spice that you must know - Republic World - Republic World
Twice-diagnosed leukaemia patient Cameron Patel reveals he has a donor after heartbreaking appeal – Leicestershire Live
By daniellenierenberg
A twice-diagnosed leukaemia patient from Leicester has found a donor after making an emotional plea from his hospital bed.
Cameron Patel was first diagnosed with the illness aged 18 after being rushed to A&E with a dangerously high heart rate.
After months of treatment at Leicester Royal infirmary he was given the all-clear in February and was looking forward to his life getting back to normal.
Despite there being a low chance of Cameron having a relapse in June this year that's exactly what happened.
The leukaemia had returned and this time doctors said he would need a bone marrow transplant.
So the search for the best possible match began.
Due to his dual heritage, the chances of finding a suitable match for him were significantly low so Cameron was told that the search would not be easy.
After celebrating his 20th birthday this month, Cameron from Knighton, Leicester has now revealed that he will be receiving a transplant from his own mother.
"My mum brought me into this world and she's keeping me here," he told LeicestershireLive.
Sarah Patel, Cameron's mum, is only a 50 per cent match for him which is less than a potential match from a stranger would be.
She said: "You support as much as you can but at the end of the day you have to watch him go through it - so to be his donor makes me really happy, even if it is just a half match."
Although every effort was made to find him a match doctors couldn't find a single donor despite looking worldwide.
Now he will have what is called a haploidentical transplant which involves a half-match from a parent.
Sarah said: "Being one of the last resorts made me feel quite worried because even though I'm his mum, a stranger could have been a higher match.
"But he can't keep having chemotherapy forever and we can't wait around too long because he relapsed quite quickly so we know the pattern of his disease now.
"It's been mixed emotions but I'd do anything for him."
In the months leading up to his transplant, which will happen on Thursday 24 October, Cameron and his mother have undergone health checks and and tests to ensure that she is well enough to be his donor.
Any signs of illness or underlying health conditions in Sarah would mean that her stem cells could not be used.
Due to the low percentage match there are risks with the haplo transplant, including graft versus host disease (GvHD) in which the donated bone marrow or stem cells attack the body due to it being foreign.
Cameron will receive conditioning therapy in which chemotherapy will prepare his body for the transplant.
Following the transplant, he will have to remain isolated for 100 days - only his sister and mum will be allowed to see him.
"I've got a few films and games for my recovery period but I can't wait to just get out," he said.
Sarah said that her daughter, Charis has been a "great support for Cameron" and herself.
"They just love each other so much," the 55-year-old said about the siblings.
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The family have coined the day of Cameron's transplant as "day 0" and will count down the days until he can start living a normal life.
"It's been a difficult year or so but I can't really process things - I'm just sort of in this sub-universe where I'm just getting on with it."
"We couldn't do it with out our friends and family and Cameron's friends have been amazing," Sarah said.
Cameron has now moved to Nottingham University Hospital for his transplant, after spending the majority of the last year at Leicester Royal Infirmary.
"To be honest, I've been a bit low about leaving, I miss the nurses and everyone in ward 27 - they're family to me," Cameron said.
"When I relapsed I was in a really bad place and the nurses would come in and watch a film with me or play cards.
"There's doing nurse duties and there's being a friend - I want to thank them for everything."
Throughout his treatment, Cameron has made it his mission to raise awareness of blood disease and how people can help.
"I'm glad that I've been able to get out once in a while to spread the message - it's all good sitting in hospital and doing it from my iPhone but it's nice to go out and see the people you're speaking to," he said.
"Once I'm out of here I want to travel a bit and then carry on spreading awareness to young people," he added.
During his time on the teenage cancer ward Leicester Royal Infirmary, Cameron became friends with Coalville Town's footballer Courtney Wildin, who was also undergoing treatment for leukaemia.
Courtney had a transplant earlier this year and has since stayed in touch with Cameron.
They plan to work together to encourage young people to join the bone marrow donor register.
"He reached out to me while we were both on the ward and we ended up becoming good friends," Courtney said.
"We're going to start off going to colleges and tell people our story."
Without the haploidentical stem cell transplant, Cameron would still be left without a single match.
He wants to help to make sure that there can be a donor for everyone.
He said: "There are a lot of people out there who need a donor - two minutes of your life could save someones entire life."
Patients with ultra-rare bone marrow disease set to benefit from 1.15m grant from LifeArc and The Aplastic Anaemia Trust – PharmiWeb.com
By daniellenierenberg
Grant will support researchers from Kings College London and Kings College Hospital to test a personalised treatment approach for Aplastic Anaemia patients who have not responded to available therapies
21 October 2019 - LifeArc, a UK-based medical research charity, and the Aplastic Anaemia Trust (AAT) have jointly awarded a 1.15m research grant to Kings College London and Kings College Hospital to investigate the potential of a novel type of personalised cellular therapy to reverse the ultra-rare condition aplastic anaemia (AA). The results of this research could give new hope to people living with a severe, life-limiting form of this condition.
The grant will fund a clinical trial to investigate the safety and efficacy of using a patients own T-reg cells to restore the blood-making function of the bone marrow. This follows laboratory-based research from the team of scientists where T-reg cells from a patients own blood were collected, selected for activity and multiplied. In a test tube, these cells prevented the immune system from attacking the patients bone marrow stem cells.[i]
Professor Ghulam Mufti, Department of Haematological Medicine at Kings College London and Kings College Hospital, and lead study investigator said: For patients with this ultra-rare disease, were looking for the first time at a personalised medicine approach where their own immune cells could be used to alter their disease. In AA there is a reduction in the number of T-regs and most of the ones that the AA patients do have are non-functional. Weve seen success in the laboratory by selecting and bolstering the number of functional T-reg cells. Now, with funding from LifeArc and the AAT, we can investigate the potential of this approach in treating AA patients who currently have very limited treatment options. AA is an ultra-rare life-threatening illness caused by the bone marrow failing to make enough of all three types of blood cellsred blood cells, white blood cells and platelets. Only around 100150 people in UK are diagnosed per year, affecting all ages but most commonly people between the ages of 10 to 20 years old and those over the age of 60 years.
People with the illness are at greater risk of infections, bleeding, and can experience extreme fatigue, which leaves them unable to carry out simple daily tasks that most people take for granted. Around one in three patients with severe AA fail to respond to existing drug treatments and the other option a bone marrow transplant is reliant on finding a suitable donor, requires life-long treatment with immunosuppression therapy and is unsuccessful in one in three people. Dr Catriona Crombie, LifeArcs Head of Philanthropic Fund explained why the charity had approved the funding: LifeArc set up the Philanthropic fund to support translational research into rare diseases, where there is less interest from commercial organisations. Patients with AA can have limited treatment options; this opportunity with Kings College London, Kings College Hospital and the AAT has the potential to transform the lives of patients living with a severe form of the disease. The trial at Kings College London and Kings College Hospital will run for a duration of three years and aims to recruit nine patients. A blood sample of the patients T-reg cells will be extracted, purified and grown in the lab before being given back to the patient in a higher concentration. As patients with AA are more susceptible to infection, this personalised treatment approach is more likely to avoid the risk of severe infection and inflammation.
Grazina Berry, CEO of the AAT said: AA can severely impact a persons quality of life. Through AATs close work with Kings College London and Kings College Hospital as a specialist centre of clinical care and research in AA, we identified the project with the most potential to directly benefit patients who are currently at a loss for solutions. We are delighted to have partnered with LifeArc and Kings College London and Kings College Hospital to progress this ground-breaking work, which could potentially enable people living with severe AA to once again lead a normal life.
Red wine-like molecule when added to gene therapy, may enable faster, more effective… – ScienceBlog.com
By daniellenierenberg
Gene therapy has broadened the treatment possibilities for those with immune system deficiencies and blood-based conditions, such as sickle cell anemia and leukemia. These diseases, which once would require a bone marrow transplant, can now be successfully treated by modifying patients own blood stem cells to correct the underlying genetic problem.
But todays standard process for administering gene therapy is expensive and time-consuminga result of the many steps required to deliver the healthy genes into the patients blood stem cells to correct a genetic problem.
In a discovery that appears in the journal Blood, scientists at Scripps Research believe they have found a way to sidestep some of the current difficulties, resulting in a more efficient gene delivery method that would save money and improve treatment outcomes.
If you can repair blood stem cells with a single gene delivery treatment, rather than multiple treatments over the course of many days, you can reduce the clinical time and expense, which removes some of the limitations of this type of approach, says Bruce Torbett, PhD, associate professor in the Department of Immunology and Microbiology, who led the research.
The new finding centers on caraphenol A, a small molecule closely related to resveratrol, which is a natural compound produced by grapes and other plants and found in red wine. Resveratrol is widely known as an antioxidant and anti-inflammatory agent. Similar to resveratrol, caraphenol A is anti-inflammatory, but in this study, it served a different role.
Torbett and his team became interested in the unique chemical properties of resveratrol and similar types of molecules and wondered if they could enable viral vectors, used in gene therapy to deliver genes, to enter blood stem cells more easily. This would be momentous because stem cellsand in particular, self-renewing hemopoietic stem cellshave many barriers of protection against viruses, making them challenging for gene therapy to infiltrate.
This is why gene therapy of hemopoietic stem cells has been hit-or-miss, Torbett says. We saw a way to potentially make the treatment process significantly more efficient.
The gene therapy treatment process currently requires isolating a very small population of hemopoietic stem cells from the blood of patients; these young cells can self-renew and give rise to all other types of blood cells. Therapeutic genes are then delivered to these cells via specially engineered viruses, called lentiviral vectors, which leverage viruses natural knack for inserting new genetic information into living cells.
However, hemopoietic stem cells are highly resilient to viral attacks. They protect themselves with structures known as interferon-induced transmembrane (IFITM) proteins, which intercept lentiviral vectors. Because of this, it can take many attemptsand a large quantity of expensive gene therapy vectorsto successfully delivery genes into hemopoietic stem cells, Torbett says.
Torbett and his team found that by adding the resveratrol-like compound, caraphenol A, to human hemopoietic stem cells, along with the lentiviral vector mix, the cells let down their natural defenses and allowed vectors to enter more easily. Once the treated stem cells were placed into mice, they divided and produced blood cells containing the new genetic information.
Another key benefit of the approach is time: If gene delivery treatment of blood stem cells can be accomplished in less time, the cells can be re-administered to the patient sooner. This not only makes treatment more convenient for the patient, but it helps to ensure the stem cells dont lose their self-renewing properties, Torbett says. The longer stem cells exist outside of the body and are manipulated, the more likely it is they will lose their ability to self-generate and ultimately correct disease.
Torbett and his team are continuing to study the underlying reasons for stem cells inherent resistance to genetic modification, with the goal of further improving treatment efficiency and reducing cost. Because many of the diseases treatable with gene therapy affect children, Torbett says he feels a special urgency to advance this discovery from the lab into the clinic.
Authors of Resveratrol trimer enhances gene delivery to hematopoietic stem cells by reducing antiviral restriction at endosomes, include Stosh Ozog, Nina D. Timberlake, Kip Hermann, Olivia Garijo, Kevin G. Haworth, Guoli Shi, Christopher M. Glinkerman, Lauren E. Schefter, Saritha DSouza, Elizabeth Simpson, Gabriella Sghia-Hughes, Raymond R. Carillo, Dale L. Boger, Hans-Peter Kiem, Igor Slukvin, Byoung Y. Ryu, Brian P. Sorrentino, Jennifer E. Adair, Scott A. Snyder, Alex A. Compton and Bruce E. Torbett.
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Red wine-like molecule when added to gene therapy, may enable faster, more effective... - ScienceBlog.com
Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Fanconi Hypoplastic Anemia Pipeline Insight Market Research Report 2019: by Trends, Development, Types,…
By daniellenierenberg
Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Pipeline Insight Market Research 2019 report by Mart Research outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Fanconi Anemia (FA) Fanconi Hypoplastic Anemia pipeline landscape is provided which includes the disease overview and Fanconi Anemia (FA) Fanconi Hypoplastic Anemia treatment guidelines. The assessment part of the report embraces, in depth Fanconi Anemia (FA) Fanconi Hypoplastic Anemia commercial assessment and clinical assessment of the pipeline products under development. In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Fanconi Anemia (FA) Fanconi Hypoplastic Anemia collaborations, licensing, mergers and acquisition, funding, designations and other product related details.
Fanconi Anemia Understanding
According to the Cancer and Blood Disorders Center, Fanconi Anemia (Fanconi hypoplastic anemia, Fanconi pancytopenia, Fanconi panmyelopathy) is a rare inherited disease characterized by multiple physical abnormalities, bone marrow failure, and a higher than normal risk of cancer. Researchers have shown that mutations in one of at least 15 different genes can cause FA. The proteins normally produced by these genes form a kind of cellular machine that helps detect and repair damaged DNA in blood stem cells and other cells in the body, in FA this damaged DNA repair is slowed. Therefore, blood stem cells (in the bone marrow) accumulate damaged DNA and do not survive. FA is usually discovered between birth and age 10-15 years; however, there also have been cases identified in adulthood. FA occurs equally in males and females. It has been identified in all ethnic groups. Researchers continue to clone and characterize the genes responsible for FA, which is bringing considerable progress in the diagnosis and understanding of this disease. It is more common in male as compared to female.
Fanconi Anemia Pipeline Development Activities
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The report is built using data and information traced from the researchers proprietary databases, company/university websites, clinical trial registries, conferences, SEC filings, investor presentations and featured press releases from company/university web sites and industry-specific third party sources, etc.
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Companies Covered in Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Pipeline Insight Mart Research:Abeona TherapeuticsRocket PharmaceuticalsCIEMATCellenkosPluristem TherapeuticsBioLineRxForesee PharmaceuticalsGamida CellAmgenNovartis
Drugs Covered in Fanconi Anemia (FA) Fanconi Hypoplastic AnemiaPipeline Insight Market Research:Research programme: rare haematological disorder gene therapiesResearch programme: gene therapiesRP L101RP L102CK 0801PLX R18MotixafortideFP 045OmidubicelRomiplostimEltrombopag
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This report provides an in-depth Commercial Assessment of therapeutic drugs have been included which comprises of collaborations, Licensing, Acquisition Deal Value Trends. The sub-segmentation is described in the report which includes Company-Company Collaborations (Licensing / Partnering), Company-Academia Collaborations, and Acquisition analysis in both Graphical and tabulated form.
Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Clinical Assessment of products
The report comprises of comparative clinical assessment of products by development stage, product type, route of administration, molecule type, and MOA type across this indication.
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Table of Content for Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Pipeline Insight Market Research Report:Chapter One: Report IntroductionChapter Two: Fanconi Anemia (Fanconi hypoplastic anemia, Fanconi pancytopenia, Fanconi panmyelopathy)Chapter Three: Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Current Treatment PatternsChapter Four: Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Mart Researchs Analytical PerspectiveChapter Five: Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Pipeline TherapeuticsChapter Six: Fanconi Anemia (FA) Fanconi Hypoplastic Anemia -Products AnalysisChapter Seven: Recent TechnologiesChapter Eight: Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Key CompaniesChapter Nine: Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Key ProductsChapter Ten: Dormant and Discontinued ProductsChapter Eleven: Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Unmet NeedsChapter Twelve: Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Future Perspectives
List of Tables for Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Pipeline Insight Market Research Report:Table 1. Diagnostic GuidelinesTable 2. Treatment GuidelinesTable 3. Assessment SummaryTable 4. Company-Company Collaborations (Licensing / Partnering) AnalysisTable 5. Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Acquisition AnalysisTable 6. Assessment by Phase of DevelopmentTable 7. Assessment by Product Type (Mono / Combination)Table 8. Assessment by Stage and Product TypeTable 9. Assessment by Route of AdministrationTable 10. Assessment by Stage and Route of AdministrationTable 11. Assessment by Molecule TypeTable 12. Assessment by Stage and Molecule TypeTable 13. Assessment by MOATable 14. Assessment by Stage and MOATable 15. Late Stage Products (Phase-III)Table 16. Mid Stage Products (Phase-II)Table 17. Early Stage Products (Phase-I)Table 18. Pre-clinical and Discovery Stage ProductsTable 19. Inactive ProductsTable 20. Dormant ProductsTable 21. Discontinued Products
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Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Fanconi Hypoplastic Anemia Pipeline Insight Market Research Report 2019: by Trends, Development, Types,...
Healthcare Terms Are Out of Touch, Says Mom Advocate – Medscape
By daniellenierenberg
This transcript has been edited for clarity.
Eric J. Topol, MD: Hello. I'm Eric Topol, editor-in-chief for Medscape. I'm thrilled to speak with Hala Durrah today, who I got to know about through a remarkable essay she wrote for Health Affairs back in March. Hala, welcome to our program.
Hala H. Durrah, MTA: Thank you for having me.
Topol: It's a real pleasure and this an important and critical topic. Your essay was "My Child Is Sick; Don't Call Her a 'Consumer.'"[1] There is so much to learn here for Medscape folks. Can you tell us a little bit about your background and your family?
Durrah: Sure. I am a patient/family engagement consultant by profession, which basically means that I work with healthcare organizations and systems around the concept of patient/family engagement, spanning anywhere from patient-centered measurements to quality improvement, and so on. I came to the work, though, not as part of a plan, but by fate and destiny. My firstborn, whose name is Ayah, was born with a very rare liver disease which we knew would require liver transplantation. She is 16 years old now, but as you can imagine, we've been on quite a journey in the healthcare system. In addition, I have four other children and my husband is an adult medical hospitalist at a major academic center on the East Coast, so healthcare is a big piece of our lives.
I realized a few years into the journey with my daughter that I wanted to become more engaged in improving healthcare and partnering with our care teamthe physicians, nurses, pharmacists, and the larger group of specialists that she was seeing on a regular basis. I had the opportunity to volunteer at a local hospital that was looking for more patient/family involvement in some of their quality improvement work, and I decided that this was definitely something I wanted to pursue further, so I did. But my daughter's healthcare journey continues and I continue to see the good, the not so good, and everything in between.
In addition, I think I have a unique perspective because my husband is a physician and works in the hospital setting. I understand and can empathize with the real challenges facing physicians that are constantly placing pressure on them and demanding their time. I am very cognizant of that, so in my work I really try to balance the voice of the patient or caregiver, and the voice of the physician or nurse, because I can definitely see all of the different perspectives. At the end of the day, I think we all really want these meaningful relationships where we communicate and empathize with one another, and at the same time, we all want the best care for each other. That is my goal and the work I've been doing for the past several years.
Topol: That is terrific. You have a panoramic view of the healthcare landscapethat's for sure.
Topol: You wrote about your daughter; it is a miracle story in so many respects. Her name, Ayah, means "sign of God"is that right?
Durrah: Yes. We named her that before I knew she was going to be born with this illness, and it's pretty remarkable that she fit that name and the meaning of her name since she was born. Her first liver transplant, unfortunately, failed within the first 24 hours. As you all know, a liver does not wait, so we were preparing to say goodbye to her when she was about 5 years old.
Subsequently, by miracle, she got another liver 2 days later. It was from the same hospital where she was at, which was even more amazing because her surgeons were prepared to travel anywhere to get another liver. She was placed number one on the nation live listing after that first transplant failed, and it's remarkable that she got another one.
Topol: After she had these two liver transplants at age 5, she got Burkitt lymphoma.
Durrah: Unfortunately, because of her therapies, and also being Epstein-Barr viruspositive, she developed stage III Burkitt lymphoma 2 years after the liver transplant, which was quite devastating, to say the least.
Topol: It required another type of transplant, a bone marrow transplant.
Durrah: Yes. Unfortunately, she had several months of a pretty intense chemotherapy regimen that ultimately failed, and we had to move to an autologous bone marrow transplant. She was not able to have donor cells because she was already an organ transplant recipient. She sat one day in the hospital with a catheter, and they took her stem cells and then gave them back to her about a month later after some more intense chemotherapy.
In all our experiences, I don't believe that physicians and nurses ever defined my daughter as a consumer.
Obviously, she has been through quite a bit. A lot goes along with being a patient of liver disease or a patient who survived cancer with all of the chemotherapy, so while her health is stable, things are constantly moving in the background that we're watching. I tell people that I sometimes look at it like a radar screen. You kind of see the little red dots bleeping and some of them get brighter and some of them get dimmer. A lot of people are monitoring those lights, but I'm the chief monitor of all of those lights and the coordinator of making sure we stay on top of them.
Topol: You are quite an advocate and it is just an amazing story. I want to get into this message that you have about using the term "consumer," because I have hated that term for years. Why do we use this term when we're talking about patients in the health world? You wrote, "I share our story because I am becoming increasingly troubled by a trend in healthcaretoward thinking of patients as 'consumers' but not actually engaging communities in healthcare improvement and innovation." Tell us a bit about this objection of this term, because I think if anybody has a right to object to the use of that term, it would be you.
Durrah: The term definitely does not resonate with me, and I share your strong feelings against the utilization of this term. Overall, I think it continues to underline and push the business imperative of healthcare versus the humanity imperative in which healthcare was initially built upon. I reject in some ways that this notion of consumerism will improve healthcare because healthcare did not start as a business imperative, nor was the framework built to support such a term.
In all of our experiences, I don't believe that physicians and nurses ever defined my daughter as a consumer. I believe [the term] distances us from one another and does not amplify or support that relationship-based care that we all seek to have and to improve. I also don't think "consumer" empowers us, although I understand why some believe it may, because the framework of healthcare is not set up in such a way where "consumer" denotes choice. A lot of healthcare is dictated to the patient or to the caregivers by their insurance companies or their lack thereof, or the communities in which they live, or by lots of different other parties that are involved in it. I'm not quite sure where the choice comes in, especially because no one chooses to be sick. A consumer has choices, but we don't have that choice.
It does not make sense to use that term. I understand where people come from wanting to empower individuals by changing the terminology [to a less] "passive" role of the patient, but I'm not quite sure that changing the terminology we use makes us equals, gives us any more choices, or improves the care we will receive.
Topol: Words are important. This term is hackneyed, it's pervasive, and I think you made the most eloquent case in the history of the medical literature because your intersection with the healthcare world is extensive.
Durrah: Oh my gosh. I'm humbled by that. I'm not sure if I deserve all that, but I appreciate it.
Topol: You have a master's degree from George Washington and you worked in tourism, and you made some interesting parallels between a consumer of tourism versus a patient. Can you talk to us about that?
Durrah: Sure. My master's is in tourism and administration, with a focus in meeting and event management, and here I am in healthcare advocacy now. But I found that it's been very useful because you do see in healthcare this shift of trying to create a tourism-type experience for healthcare. And generally speaking, tourism is a choice; we all choose to travel or to use a certain hotel or rental car company because we've had experiences. Most of the time, you come back from a vacation with great memories, and when you share those memories with others, they may want to have the same experiences as you.
But I don't believe that we can really equate healthcare to a vacation. I'm not quite sure who would utilize that same experience as a vacation. Things that healthcare has that no other industry has are the trauma, pain, and anguish that go into being either a patient or the caregiver of someone. I think physicians and nurses have a lot of emotions in the healthcare experience that you could never find in tourism. And tourism tries to have a constant feedback loop with their customers or consumers; healthcare does not. Yes, we tout these wonderful surveys that are supposed to increase patient satisfaction, but were any of them co-designed with the communities the health systems serve? The answer is no. Do they allow you to really respond in such a way that will provide meaningful data using stories of your experiences in the system? No. So again, trying to equate the healthcare experience with the lessons learned from tourism is a mismatch.
Topol: Right. Even that term "medical tourism" is about a different concept.
There are many parts of your daughter's story that were really touching and deep, but one of the things that stood out was how her liver doctor would hold your hand, and how that was not about consumerism but, as you say, a choice driven by humanity and compassion. This, I think, speaks to the stark dramatic differences between the terms.
Topol: Another term I'm interested in asking you about is "providers." It's another term I don't care for. Should that term be used?
Durrah: It's interesting, because I believe that in the article I do reference "care providers" at one point. Initially when I started in this work, I always [used the specific terms of] "physicians," "nurses," "pharmacists," and so on. All of a sudden that term "provider" got thrown into the mix, and I adapted it because it seemed that everyone was using it to cover all the members of the care team that might interact or touch a patient. I'm guilty of using that term and I got a lot of response after my article came out, particularly from physicians, about how the term "provider" was not liked. I believe the term came about with this whole business imperative/push in healthcare. Insurance companies use that term and healthcare systems have now adopted that term as well, and it probably is in play because of this whole consumerism push as well.
I did prefer saying "physicians" or "nurses" or "pharmacists" and that we're all part of the "care team." I prefer that terminology, just as I prefer to be called a "partner" in my care versus a "consumer" or a "customer." I think that the term does not fit the role that physicians and nurses play. They are not just a provider. I look at them as part of my team and I'm on their team, so we're all working together. I think "provider" also sounds a little bit like a hierarchy. It does not suggest that notion of that partnership and just reinforces a distance. Consumerism is kind of defined by this transactional relationship, so you would use that term to reinforce that. I see how it has developed and how it's being pushed, and I think it's all related to the business of medicine versus the actual human experience and the humanity of medicine.
We so largely lost the 'care' in 'healthcare.
Topol: These terms got adopted when healthcare was transformed to a business, and now we're relooking at this.
Your work and eloquence and what you continue to do as an advocate in patient care will help us get back on track. It's just one of many things we need to do.
Topol: You also brought up the term "lean principles." It would be interesting for you to just touch on this as well.
Durrah: I've noticed in my work in healthcare thus far that health systems are adopting a lot of frameworks. One of these is becoming "lean" or utilizing "lean principles," which are driven by efficiency and cost savings.
Typically, those who advocate for lean principles within health systems say, "This is going to benefit everyone: physicians, nurses, patients and families, and the communities we serve." But if you really dig down deep, I don't think it has trickled down at all to any cost savings for patients or families. I don't think it's improved quality for communities which the healthcare system serves. And I certainly don't see physicians and nurses not being more burned out or more extended. They get affected by lean principles, where staffing is cut in order for that cost savings to occur. They are being told to do 150 things versus 100 things a day.
When I first learned about "lean" and read about it, I thought it sounded great. But then when I got deeper into this work, I thought, "Wait a minutewho is this benefiting other than the bottom line of healthcare systems?" It's really interesting how healthcare tends to cherry-pick principles or terminology from other industries with the goal of trying to improve healthcare, when it's really not doing that. It's simply putting a Band-Aid on one problem and creating a new one.
Topol: We so largely lost the "care" in "healthcare." You referred to the "care team." You undoubtedly experienced that with your daughter, and we want to bring it back. We should be more precise about language and avoid business terms, and talk about clinicians as doctors, nurses, pharmacists, physical therapists, or whoever. We should be more specific than using this "provider" term which obviously could be a relative or a friend.
Topol: What response did you receive from the essay you wrote in Health Affairs? It clearly resonated, and when I posted it on Twitter, there was quite a bit of response.
Durrah: I got an incredible response from the article, and I appreciate you tweeting and retweeting it because a lot of people saw that and reached out to me and started retweeting as well. A number of people sent me personal emails and messages, and I really was humbled by the response. I was quite nervous to write the article I did because in my work, there is kind of a fine line that you can only push the boundary so far, and then if you push them too far you get a lot of pushback. I sometimes feel like I'm this one little patient advocate voice among all these other voices. The article really resonated with physicians in particular, and they really understood the story which I shared about my daughter's liver doctor.
When we found out that she was diagnosed with cancer, she asked to sit in the meeting with the oncologists. She didn't have to do that, but she wanted to. I said, "Of course you can join us." She sat next to me and held my hand the entire meeting. Every time they said something distressing, she would just squeeze my hand, but she didn't utter a word. I think that encapsulates the relationship that patients and caregivers have with their physician or nurse. It's such a special bond, and the term "consumer" could never define that particular bond; she would never look at this as a transactional relationship. Would "consumer" teach her to do that? No. As you said before, it is the humanity and compassion of medicine, and that is why most everyone who comes into the profession really wants to help humanity and give that empathy and compassion.
We have a lot to learn, and it's going to take many voices to speak up and push back against consumerism because some pretty large organizations and groups are trying to push consumerism and continue this business imperative of healthcare that is motivated by bottom lines. I think we're going to get there. Maybe we're already there. We're at a tipping point. There is so much dissatisfaction, and so many parts of the system are broken. To say that consumerism will give you more choices, shorter wait times, and maybe even price transparency, even though you still have to deal with your insurance provider or lack thereof, makes me giggle because I don't think that is going to be the solution.
The only solution I see is that we have to partner with one another and co-create solutions to improve healthcare as teamsequal voices at the tableand begin this pushback. If we don't, I fear what is ahead because I've already had a glimpse of it. I'm nervous because as my daughter slowly moves into adulthood, and she is almost there, these were the things I hoped we would have conquered before she got to that point. A lot of this is pushing us away from one another and distancing ourselves from one another, and that is not going to change healthcare.
Topol: You said it so well. I've been eager to meet you since I read your work months ago, and I wanted the whole Medscape audience to get to know you and your story. Most of them are not on Twitter and most don't read Health Affairs. Your story is so darn important, and you convey it in a powerful way.
I'm so glad to know that your daughter is okay, having gone through 16 years of rough times, especially in her earlier years. I just want you to carry on. You are an important voice. You may qualify yourself as only one, but it's a powerful one, and very few people have had an experience like yours. You're in a rarified group and can transmit the emotion and the sense of caring. Let's get these words right, and let's zap "consumer" from this story of future healthcare.
Thanks so much for joining us today on Medscape, and we will look forward to following you and learning more from you in the future.
Durrah: Thank you. I look forward to partnering with your audience on improving healthcare.
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Healthcare Terms Are Out of Touch, Says Mom Advocate - Medscape
Best Growth Report On Autologous Stem Cell Based Therapies Market Survey 2019 Industry Outlines, Future Trends, Forecasts And Regional Segmented…
By daniellenierenberg
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Hemostemix Announces Positive Results and Conclusions Reported in Phase II CLI Trial Abstract – GlobeNewswire
By daniellenierenberg
CALGARY, Alberta, Oct. 21, 2019 (GLOBE NEWSWIRE) -- Hemostemix Inc. (Hemostemix or the Company) (TSX VENTURE: HEM; OTCQB: HMTXF), a biotechnology company developing and commercializing blood-derived stem cell therapies for unmet medical conditions, is pleased to provide a summary of the presentation entitled Autologous Stem Cell Treatment for CLI Patients with No Revascularization Options: An Update of the Hemostemix ACP-01 Trial With 4.5 Year Followup. Lead investigator Dr. York Hsiang, Professor of Vascular Surgery, University of British Columbia gave this update at the 41st Annual Canadian Society for Vascular Surgery Meeting on September 14, 2019.
Dr. Hsiang reported on the blinded results from the long-term follow-up of the first cohort of patients enrolled at two trial sites, Vancouver Coastal Health Research Institute (VCHRI) located in Vancouver, BC, led by principal investigator, Dr. York N. Hsiang, MB, ChB, MHSc, FRCSC and University Health Network, Peter Monk Cardiac Centre located in Toronto, Ontario, led by principal investigator Dr. Thomas Lindsay, MDCM, MSc, FRCSC, FACS.
Following is a summary of the results and conclusion:
In addition, the Companys Data Safety Monitoring Board (DSMB) recently met to review patient safety data in the ongoing Phase II clinical trial for CLI. The DSMB did not find safety concerns with ACP-01 and recommended continuing to enroll patients in the trial. The clinical trial is ongoing at 13 clinical sites in the US and Canada, with several additional sites in the process of being initiated. To date, 46 of the planned 95 patients have been enrolled and treated in the study.
We are very pleased with these blinded long term follow up results, and the recommendation of the DSMB, which are consistent with the findings reported in our two previous published studies of ACP-01 in CLI patients, said Dr. Alan Jacobs, President and Chief Medical Officer of Hemostemix. Patients with critical limb ischemia face a high rate of amputation when revascularization treatment options are exhausted, so seeing this level of improvement, and outcomes maintained for up to 4.5 years after treatment, is extremely encouraging.
ABOUT HEMOSTEMIX INC.
Hemostemix is a publicly traded clinical-stage biotechnology company that develops and commercializes innovative blood-derived cell therapies for medical conditions not adequately addressed by current treatments. It is one of the first clinical-stage biotech companies to test a stem-cell therapy in an international, multicenter, Phase II clinical trial for patients with critical limb ischemia (CLI), a severe form of peripheral artery disease (PAD) caused by reduced blood flow to the legs. The Phase II trial targets a participants diseased tissue with proprietary cells grown from his or her blood that can support the formation of new blood vessels. The Companys intellectual property portfolio includes over 50 patents issued or pending throughout the world. Hemostemix has a manufacturing contract with Aspire Health Science, LLC (Aspire), for the production of ACP-01 and for research and development purposes at Aspires Orlando, Florida, facility. Building towards commercialization, Hemostemix has also licensed the use, sale and import of ACP-01 for certain indications to Aspire in certain jurisdictions. The Company is continuing research and development of its lead product, ACP-01 with other applications, including cardiovascular, neurological and vascular indications.
For more information, please visit http://www.hemostemix.comor email office@hemostemix.com.
Contact:
Kyle Makofka, CEOSuite 2150, 300 5th Avenue S.W.Calgary, Alberta T2P 3C4Phone: (403) 506-3373E-Mail: kmakofka@hemostemix.com
Neither the TSX Venture Exchange nor its Regulation Service Provider (as that term is defined under the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.
Forward-Looking Statements
This release may contain forward-looking statements. Forward-looking statements are statements that are not historical facts and are generally, but not always, identified by the words expects, plans, anticipates, believes, intends, estimates, projects, potential, and similar expressions, or that events or conditions will, would, may, could, or should occur. Although Hemostemix believes the expectations expressed in such forward-looking statements are based on reasonable assumptions, such statements are not guarantees of future performance and actual results may differ materially from those in forward-looking statements. Forward-looking statements are based on the beliefs, estimates, and opinions of Hemostemix management on the date such statements were made. By their nature forward-looking statements are subject to known and unknown risks, uncertainties, and other factors which may cause actual results, events or developments to be materially different from any future results, events or developments expressed or implied by such forward-looking statements. Such factors include, but are not limited to, the Companys stage of development, future clinical trial results, long-term capital requirements and future ability to fund operations, future developments in the Companys markets and the markets in which it expects to compete, risks associated with its strategic alliances and the impact of entering new markets on the Companys operations. Each factor should be considered carefully and readers are cautioned not to place undue reliance on such forward-looking statements. Hemostemix expressly disclaims any intention or obligation to update or revise any forward-looking statements whether as a result of new information, future events, or otherwise.
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Hemostemix Announces Positive Results and Conclusions Reported in Phase II CLI Trial Abstract - GlobeNewswire
Bayer Announces Recipients of the Pulmonary Hypertension Accelerated Bayer (PHAB) Awards at CHEST Annual Meeting 2019 – BioSpace
By daniellenierenberg
WHIPPANY, N.J., Oct. 21, 2019 /PRNewswire/ -- Bayer today announced recipients of the inaugural Pulmonary Hypertension Accelerated Bayer (PHAB) Awards, a U.S.-based research grant program created to support clinical research in pulmonary hypertension (PH), with a focus on pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The recipients will receive a combined total of $1 million in grants over a two-year period, making the PHAB Awards one of the largest industry-funded grant programs focused on PAH and CTEPH in the U.S. The eight award recipients were formally announced at a ceremony during the American College of Chest Physicians (CHEST) Annual Meeting in New Orleans on Sunday, October 20, 2019.
"Supporting a new generation of researchers is imperative to ensure we continue the progress that has been made during the past decade in pulmonary hypertension and its related conditions," said Aleksandra Vlajnic, M.D., Senior Vice President & Head Medical Affairs Americas at Bayer. "Our hope is that the PHAB Awards program will encourage researchers to think creatively about solving the significant treatment and patient care challenges that remain, knowing Bayer is committed to providing the support needed to help bring those ideas to fruition. We want to congratulate all of the applicants on their winning proposals."
The recipients are:
The PHAB Awards recipients were selected by an independent Grants Review Committee, consisting of the following eminent PH leaders:
"I would like to thank and recognize the Grants Review Committee for their time and commitment, and the PH community in the U.S. for their overwhelming response to the inaugural PHAB Awards," said Sameer Bansilal, M.D., M.S., Medical Director, U.S. Medical Affairs at Bayer. "We look forward to an even greater response next year and encourage eligible applicants to start thinking about submitting their research proposals."
The PHAB Award eligibility, review and category criteria were modeled after the National Institutes of Health (NIH) system; entries were graded on significance, investigator(s), innovation, approach, and environment.
For more information on the PHAB Awards visit: https://www.phab-awards.com/awards/or e-mail PHAB.awards@bayer.com.
Grants were made on the merits of the research, and research must be posted on ClinicalTrials.gov. Every effort should be made to publish or present study outcomes. If the research is not conducted the grant must be returned.
About Pulmonary Arterial Hypertension (PAH)Pulmonary Arterial Hypertension (PAH, WHO Group 1) is defined by elevated pressure in the arteries going from the right side of the heart to the lungs. Typical symptoms of PAH include shortness of breath on exertion, fatigue, weakness, chest pain and syncope. PAH is caused by abnormalities in the walls of the pulmonary arteries.1,2
About Chronic Thromboembolic Pulmonary Hypertension (CTEPH)Chronic Thromboembolic Pulmonary Hypertension (CTEPH, WHO Group 4) is a progressive type of pulmonary hypertension, in which it is believed that thromboembolic occlusion (organized blood clots) of pulmonary vessels gradually lead to an increased blood pressure in the pulmonary arteries, resulting in an overload of the right heart.3,4 CTEPH may evolve after prior episodes of acute pulmonary embolism, but the pathogenesis is not yet completely understood. The standard and potentially curative treatment for CTEPH is pulmonary thromboendarterectomy (PTE), a surgical procedure in which the blood vessels of the lungs are cleared of clot and scar material.5,6 However, a considerable number of patients with CTEPH (20%-40%) are not operable and in up to 35 percent of patients, the disease persists or reoccurs after PTE.7
About BayerBayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2018, the Group employed around 117,000 people and had sales of 39.6 billion euros. Capital expenditures amounted to 2.6 billion euros, R&D expenses to 5.2 billion euros. For more information, go to http://www.bayer.us.
Our online press service is just a click away: http://www.bayer.us/en/newsroomFollow us on Facebook: http://www.facebook.com/pharma.bayerFollow us on Twitter: https://twitter.com/Bayerus
Media Contact:David Patti, +1-973-452-6793Bayer, U.S. Product Communicationsdavid.patti@bayer.com
Forward-Looking StatementsThis release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer's public reports which are available on the Bayer website at http://www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.
References:1Galie et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart. 2016;37:67119.2American Lung Association. Pulmonary Hypertension. Accessed November 22, 2017. http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/pulmonary-hypertension.3Piazza G and Goldhaber SZ. Chronic thromboembolic pulmonary hypertension. N Engl J Med. 2011; 364: 351-360.4 Simonneau G et al. Updated Clinical Classification of Pulmonary Hypertension. Journal of the American College of Cardiology. 2013; 62(25):5 D'Armini M. Diagnostic advances and opportunities in chronic thromboembolic pulmonary hypertension. Eur Respir Rev. 2015; 24: 253262.6 Kim et al. Chronic thromboembolic pulmonary hypertension. J Am Coll Cardiol. 2013; 62: D92-9.7 Mathai et al. Quality of life in patients with chronic thromboembolic pulmonary hypertension. Eur Respir J. 2016 Aug; 48(2): 526537.
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Bayer Announces Recipients of the Pulmonary Hypertension Accelerated Bayer (PHAB) Awards at CHEST Annual Meeting 2019 - BioSpace
More awareness needed on stem cell donation: expert – The Hindu
By daniellenierenberg
Hematopoietic stem cell transplantation (HSCT), popularly known as bone marrow transplantation (BMT), is a curative modality for a number of benign and malignant blood disorders, said Dr. Murali Krishna Voonna, surgical oncologist and managing director of Mahatma Gandhi Cancer Hospital and Research Institute.
Speaking at an awareness programme on stem cell donation organised here by the hospital, in association with Datri Blood Stem Cell Donor Registry, he said hematopoietic stem cells are immature cells that can develop into all types of blood cellswhite blood cells, red blood cells, and platelets. They are found in the peripheral blood and bone marrow.
A sizeable population are diagnosed to have benign diseases such as thalassemia major, sickle cell anaemia and aplastic anaemia, and the HSCT is among the efficient curative measures. Acute leukaemia and other blood cancers also need this procedure, he said.
Highlighting that stem cell donation and a registry are vital, Dr. Muralikrishna explained for a successful hematopoietic stem cell transplant, the patients genetic typing (HLA typing) needs a close match with that of the donor. Every patient has 25% chance of finding a match within the family, he said.
Dr. Muralikrishna stated that in such cases, finding a donor is a pressing need. There are over 80 donor registries and more than 30 million registered donors across the globe, with a very few Indians being a part of it. This reduces the chances of finding a possible match for patients of Indian origin. Patients are more likely to find a possible match within their ethnicity, which means people sharing the same cultural linguistic and biological traits, he explained.
The problem can be solved if the donors enroll themselves with a registry which will store the stem cell details and the details. Pledging to donate stem cells is easy like swabbing the inner-cheek. The donors are contacted if patients have HLA matching, he said, adding that the stem cell donation was carried out only when a match was found for a patient, not when one pledge to donate.
A blood stem cell collection centre was inaugurated at the hospitals premises on the occasion. Earlier, to avail of such service and for HLA-typing, one has travel to Hyderabad and Chennai, Dr. Muralikrishna said.
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More awareness needed on stem cell donation: expert - The Hindu
Students from over 50 universities across the UK help blood cancer charity – FE News
By daniellenierenberg
150,000 POTENTIAL STEM CELL DONORS ARE GIVING BLOOD CANCER PATIENTS HOPE THANKS TO ONE UNIVERSITY SOCIETY -1 in 4 stem cell donors are now recruited by Marrow university societies
Students from over 50 universities across the UK have helped blood cancer charity Anthony Nolan recruit an incredible 150,000 students to the Anthony Nolan stem cell register, since the first Marrow group was created 21 years ago.
Marrow is the name given to blood cancer charity Anthony Nolans network of student volunteer groups.
The first Marrow society was created at the University of Nottingham, with the aim of recruiting students to the Anthony Nolan stem cell register. For many people with blood cancers or blood disorders, receiving stem cells from a stranger is their best chance of survival.
Research has found that younger donors are more likely to save the lives of patients, so the work done by Marrow is invaluable. Over a quarter of all stem cell donations that have occurred in the last two years were from donors recruited by Marrow. University students across the country are continually giving people with blood cancer and blood disorders a second chance of life.
Liam Du Ross, 24, from North Wales is a research chemist and signed up to the Anthony Nolan register in September 2014, while at Bangor University.
Liam said: I was at my university freshers fair and stopped to talk to the volunteers running the Marrow stall. I wanted to help someone in need, and I had already signed up to donate blood at this point, so the Anthony Nolan stem cell register seemed like the next step.
Earlier this year Liam received a call to say that he had been found to be a match for someone in desperate need of a stem cell transplant.
When I found out that I was a match for someone, I felt really lucky. I had absolutely no doubts about going through with the donation at all, the whole experience was a pleasure. The nurses involved in the process were exceptional, and they helped to put me at ease. I donated via PBSC (peripheral blood stem cell collection) so I was able to lie there and catch up on podcasts and TV shows!
I thought about my recipient a lot during my donation and how I would feel if I were in their situation. I would love to meet them one day and I hope they feel the same.
To anyone thinking of signing up to the register, I would say that you should absolutely sign up. If someone you knew was that person who needed a transplant, you'd want to doeverythingin your power to help them.
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Shaswath Ganapathi, 21, is a 4th year medical student at Birmingham University and the secretary of Birmingham Marrow. He decided to volunteer with Marrow after his friend, Rohan, sadly died from leukaemia last year. Shaswath and the other committee members hold events across their university, where they encourage students to sign up to the Anthony Nolan stem cell register, any of whom could go on to donate their stem cells in the future.
Shaswath said: The donors I have spoken to have said that its the most life changing thing they have ever done, and they would never have thought that spending a few minutes signing up at a stand and doing a quick cheek swab could lead to potentially saving someones life.
Aisling Cohn, Youth Programmes Manager at Anthony Nolan, said: Marrow really are the unsung heroes helping Anthony Nolan give hope to patients with blood cancer, by signing up an incredible number of potential donors to the stem cell register. Any one of these people could save the life of someone with blood cancer.
It costs 40 to add each new person to the Anthony Nolan register, any money raised by Marrow will directly help save lives. They really are lifesavers!
If a patient has a condition that affects their bone marrow or blood, then a stem cell transplant may be their best chance of survival. Doctors will give new, healthy stem cells to the patient via their bloodstream, where they begin to grow and create healthy red blood cells, white blood cells and platelets.
Marrow
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Students from over 50 universities across the UK help blood cancer charity - FE News
Stem cell therapy is for animals too – SciTech Europa
By daniellenierenberg
Stem cell therapy for animals has seen breakthroughs
Stem cell therapy is increasingly becoming a more mainstream form of medicine. Usually applied to humans, the use of this regenerative treatment is now also being extended to animals including cats and dogs. Regenerative medicine, particularly stem cell treatment has seen many advancements in recent years with some groundbreaking studies coming to light.
Taking the cells from bone marrow, umbilical cords, blood or fat, stem cells can grow to become any kind of cell and the treatment has seen many successes in animals. The regenerative therapy has been useful particularly for treatment of spinal cord and bone injuries as well as problems with tendons, ligaments and joints.
Expanded Potential Stem Cells (EPSCs) have been obtained from pig embryos for the first time. The cells offer groundbreaking potential for studying embryonic development and producing transnational research in genomics and regenerative medicine, biotechnology and agriculture.
The cells have been efficiently derived from pig preimplantation embryos and a new culture medium developed in Hong Kong and Cambridge enabled researchers from the FLI to establish permanent embryonic stem cell lines. The cells have been discovered in a collaboration between research groups from the Institute of Farm Animal Genetics at the Friedrich-Loeffler-Institut (FLI) in Mariensee, Germany, the Wellcome Trust Sanger Institute in Cambridge, UK and the University of Hong Kong, Li Ka Shing Faculty of Medicine, School of Biomedical Sciences.
Embryonic stem cells (ESC) are derived from the inner cells of very early embryos, the so-called blastocysts. Embryonic stem cells are all-rounders and can develop into various cell types of the body in the culture dish. This characteristic is called pluripotency. Previous attempts to establish pluripotent embryonic stem cell lines from farm animals such as pigs or cattle have resulted in cell lines that have not really fulfilled all properties of pluripotency and were therefore called ES-like.
Dr Monika Nowak-Imialek of the FLI said: Our porcine EPSCs isolated from pig embryos are the first well-characterized cell lines worldwide. EPSCs great potential to develop into any type of cell provides important implications for developmental biology, regenerative medicine, organ transplantation, disease modelling and screening for drugs.
The stem cells can renew themselves meaning they can be kept in culture indefinitely, and also show the typical morphology and gene expression patterns of embryonic stem cells. Somatic cells have a limited lifespan, so these new stem cells are much better suited for long selection processes. It has been shown that these porcine stem cell lines can easily be modified with new genome editing techniques such as CRISPR/Cas, which is particularly interesting for the generation of porcine disease models.
The EPSCs have a high capacity to develop not only into numerous cell types of the organism, but also into extraembryonic tissue, the trophoblasts, making them very unique and lending them their name. This capacity could prove valuable for the future promising organoid technology, where organ-like small cell aggregations are grown in 3D aggregates that can be used for research into early embryo development, various disease models and testing of new drugs in petri dishes. In addition, the authors were able to show that trophoblast stem cells can be generated from their porcine stem cells, offering a unique possibility to investigate functions or diseases of the placenta in vitro.
A major hurdle to using neural stem cells derived from genetically different donors to replace damaged or destroyed tissues, such as in a spinal cord injury, has been the persistent rejection of the introduced material (cells), necessitating the use of complex drugs and techniques to suppress the hosts immune response.
Earlier this year, an international team led by scientists at University of California San Diego School of Medicine successfully grafted induced pluripotent stem cell (iPSC)-derived neural precursor cells back into the spinal cords of genetically identical adult pigs with no immunosuppression efforts. The grafted cells survived long-term, displayed differentiated functionality and caused no tumours.
The researchers also demonstrated that the same cells showed similar long-term survival in adult pigs with different genetic backgrounds after only short course use of immunosuppressive treatment once injected into injured spinal cord.
Senior author of the paper Martin Marsala, MD, professor in the Department of Anesthesiology at UC San Diego School of Medicine said: The promise of iPSCs is huge, but so too have been the challenges. In this study, weve demonstrated an alternate approach.
We took skin cells from an adult pig, an animal species with strong similarities to humans in spinal cord and central nervous system anatomy and function, reprogrammed them back to stem cells, then induced them to become neural precursor cells (NPCs), destined to become nerve cells. Because they are syngeneic genetically identical with the cell-graft recipient pig they are immunologically compatible. They grow and differentiate with no immunosuppression required.
Co-author Samuel Pfaff, PhD, professor and Howard Hughes Medical Institute Investigator at Salk Institute for Biological Studies, said: Using RNA sequencing and innovative bioinformatic methods to deconvolute the RNAs species-of-origin, the research team demonstrated that pig iPSC-derived neural precursors safely acquire the genetic characteristics of mature CNS tissue even after transplantation into rat brains.
NPCs were grafted into the spinal cords of syngeneic non-injured pigs with no immunosuppression finding that the cells survived and differentiated into neurons and supporting glial cells at all observed time points. The grafted neurons were detected functioning seven months after transplantation.
Then researchers grafted NPCs into genetically dissimilar pigs with chronic spinal cord injuries, followed by a transient four-week regimen of immunosuppression drugs again finding long-term cell survival and maturation.
Marsala continued: Our current experiments are focusing on generation and testing of clinical grade human iPSCs, which is the ultimate source of cells to be used in future clinical trials for treatment of spinal cord and central nervous system injuries in a syngeneic or allogeneic setting.
Because long-term post-grafting periods between one and two years are required to achieve a full grafted cells-induced treatment effect, the elimination of immunosuppressive treatment will substantially increase our chances in achieving more robust functional improvement in spinal trauma patients receiving iPSC-derived NPCs.
In our current clinical cell-replacement trials, immunosuppression is required to achieve the survival of allogeneic cell grafts. The elimination of immunosuppression requirement by using syngeneic cell grafts would represent a major step forward said co-author Joseph Ciacci, MD, a neurosurgeon at UC San Diego Health and professor of surgery at UC San Diego School of Medicine.
Other recent advancements include the advancement toward having a long-lasting repair caulk for blood vessels. A new method has been for generating endothelial cells, which make up the lining of blood vessels, from human induced pluripotent stem cells. When endothelial cells are surrounded by a supportive gel and implanted into mice with damaged blood vessels, they become part of the animals blood vessels, surviving for more than 10 months.
The research was carried out by stem cell researchers at Emory University School of Medicine and could form the basis of a treatment for peripheral artery disease, derived from a patients own cells.
Young-sup Yoon, MD, PhD, who led the team, said: We tried several different gels before finding the best one. This is the part that is my dream come true: the endothelial cells are really contributing to endogenous vessels.
When cells are implanted on their own, many of them die quickly, and the main therapeutic benefits are from growth factors they secrete. When these endothelial cells are delivered in a gel, they are protected. It takes several weeks for most of them to migrate to vessels and incorporate into them.
Other groups had done this type of thing before, but the main point is that all of the culture components we used would be compatible with clinical applications.
This research is particularly successful as previous attempts to achieve the same effect elsewhere had implanted cells lasting only a few days to weeks, using mostly adult stem cells, such as mesenchymal stem cells or endothelial progenitor cells. The scientists also designed a gel to mimic the supportive effects of the extracellular matrix. When encapsulated by the gel, cells could survive oxidative stress inflicted by hydrogen peroxide that killed unprotected cells. The gel is biodegradable, disappearing over the course of several weeks.
The scientists tested the effects of the encapsulated cells by injecting them into mice with hindlimb ischemia (restricted blood flow in the leg), a model of peripheral artery disease.
After 4 weeks, the density of blood vessels was highest in mice implanted with gel-encapsulated endothelial cells. The mice were nude, meaning genetically immunodeficient, facilitating acceptance of human cells.
The scientists found that implanted cells produce pro-angiogenic and vasculogenic growth factors. In addition, protection by the gel augmented and prolonged the cells ability to contribute directly to blood vessels. To visualise the implanted cells, they were labelled beforehand with a red dye, while functioning blood vessels were labelled by infusing a green dye into living animals. Implanted cells incorporated into vessels, with the highest degree of incorporation occurring at 10 months.
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Stem cell therapy is for animals too - SciTech Europa
We Have Celeb Facialists on Speed DialThese Are the Retinol Serums They Love – Yahoo Lifestyle
By daniellenierenberg
Confession time: As a beauty editor who chats with industry-leading derms and celebrity estheticians more often than I talk to my parents (sorry, Mom and Dad!), I'm still confused about retinol. How does retinol differ from Retin-A? How and when it should be applied? Who should or shouldn't use it? Is this how Nancy Wheeler felt when she she stepped into the Upside Down for the first time? (I mean, we've all heard retinoid-related horror stories involving irritation, peeling, and the like.)
That said, at 26, I'm the exact age experts say to start using retinol, and considering my complexion is often bogged down with annoying congestion and dullness, adding the ingredient into my nightly lineup has been on my to-do list for a while now. There are tons of amazing formulas out there, and some of the best come in the form of easy-to-use serums. And since I'm lucky enough to have some of the best skin experts in the industry on speed dial, it only made sense to reach out for guidance.
From the basics on retinol to the exact serums the pros use on themselves, we have you covered. Keep scrolling for everything you ever wanted to know about retinol serums, plus the most important shopping picks to get you started.
According to celebrity esthetician Vanessa Hernandez, who has her own skincare practice in Brentwood, California, retinol is a derivative of vitamin A, and is a softer, more gentle version of Retin-A. As for its *many* benefits, it naturally exfoliates the top layer of skin, which in turn exposes a clear, glowing, more youthful complexion.
Oh, and we're not done: She tells us the buzzy ingredient can also help minimize the appearance of pores, soften fine lines, kill acne-causing bacteria, and promote cell turnover, plus it has been clinically proven to be one of the most effective products in the role of anti-aging.
As for how retinol serums are different than other retinoid-containing formulas, they don't require a prescription and are typically more gentle since they're paired with other ingredients to soothe and nourish the skin. They're also approved for daily use since they're less intense.
"Retinol serums are a great option if you are prone to congestion and breakouts since they won't have oils and will likely feel lighter on the skin in comparison to a retinol-containing cream," says Vanessa Lee, RN, founder of L.A. beauty concept bar The Things We Do.
"If you're dry and want something that feels richer on the skin and contains some kind of moisturizing ingredient, a retinol cream (versus a serum) may be a better choice for you," Lee adds. "They both aim for the same result, but the two different carriers of the retinol are suitable for different skin types. It's great to have choices!"
Biossance Squalane + Phyto-Retinol Serum ($72)
"Retinol serums should be used at night after you cleanse and before you moisturize," confirms celebrity esthetician Shani Darden. Since our skin is in repair mode overnight, that's the most beneficial time to use a retinol serum. Plus, retinol can make your skin more sensitive to the sun, so it's best to leave it for nighttime only and make sure you're wearing sunscreen during the day.
If you have extra-sensitive skin, however, heed Lee's advice and apply your retinol OVER your moisturer of choice. "I usually educate patients on putting on treatment serums directly after washing the face, but vitamin A is a strong ingredient, and it can actually penetrate through your moisturizer," she tells us. "If you're extra sensitive, you can also use your favorite facial oil a few minutes after you place your retinol on."
That said, Lee also points out that women who are pregnant or breastfeeding are advised to skip retinol, since what we put on our skin can enter our bloodstreamand, in turn, baby's. But for the most part (and as long as you tread carefully with high-quality formulas!), anyone can use retinol serums.
"Even clients with sensitive skin can benefit from retinol if used less frequently and in lower doses," she explains. "You have the control, so it's all about getting started slowly, and graduating in frequency and/or strength as you continue. I recommend my patients to start using a gentle retinol serum once to twice a week for a few weeks, and using it up to three to four times a week as tolerated."
For best results, it's also imperative to keep an eye on your skin and how it's reacting to your retinol application. They're designed to be exfoliating (that's where the glowy magic comes from!), so if you get slightly dry or irritated while the dead skin cells are being shed from the retinol use, make sure to use a soothing serum or moisturizer, or even hydrocortisone 1% as a spot treatment.
Lee assures us that this is all par for the course when using retinolwith the right T.L.C., you'll still be able to reap all the amazing benefits. Oh, and make sure to wear a good sunscreen every single day! That's non-negotiable.
"I always look to see if retinol is within the first five to seven ingredients listed, which will ensure that retinol's a priority ingredient for the product," Lee advises. "However, because retinolcan go by so many names (retinyl acetate, propionic acid, retinol, etc.), and percentage or retinol disclosure isn't required for OTC products by the FDA, it can be a bit confusing on what to look out for in the ingredients."
Lee recommends choosing a retinol serum from a company you already love and trust, and have experience with as far as products go. Since most trustworthy skincare brands have some kind of retinol formula, she recommends starting your research there, and also discussing your options with a dermatologist or esthetician.
Below, Lee, Hernandez, and Darden share the best retinol serums they use or recommend to their clients. Keep scrolling!
The Things We Do Do Over Advanced Retinol Serum 2.5% ($72)
"This is a botanical retinol serum suitable for all skin tones, and it's 98% natural," Lee shares. "Women of color are more prone to PIH, and most efficacious retinol formulas cause a bit of dryness and irritation before the pretty results of regular use set in. This retinol is strong enough to guarantee results, but is strategically paired with nourishing ingredients like hyaluronic acid, organic jojoba, vitamin E, and gotu kola for gentle delivery and lowered risk of PIH."
Shani Darden Retinol Reform ($95)
"This is a great retinol that combines with fan-favorite, lactic acid, for major brightening and is stabilized at a low PH for even deeper exfoliation," Lee says. "Lactic acid is an alpha-hydroxy acid that helps with brightening the skin as well as preventing acne, so pairing this with retinol is a winning combo."
"Retinol Reform was the first product I ever released," Darden notes. "I created Retinol Reform to provide all of the benefits of a prescription retinol without any of the drawbacks. It features lactic acid to provide immediate brightening benefits and retinol for more long-term results."
Sunday Riley A+ High-Dose Retinol Serum ($85)
"This is retinol serum has a combination of CoQ10, which helps UV exposed skin, and Hawaiian white honey, which is rich in phytonutrients to help protect the skin while exfoliating," Lee tells us.
Chantecaille Retinol Intense+ ($140)
"This retinol serum is a luxe option that combines pure retinol with magnolia bark, vitamin C, and coffee for extra firming and brightening," says Lee. "Chantecaille is known for its pure, botanical-based ingredients in skincare and makeup, and this retinol is not to be skipped."
Naturopathica Retinol Renewal Concentrate ($38)
"This serum is an option for a gentle retinol that yields the power of argan plant stem cells to aid repair in the skin while retinol is hard at work at increasing cell turnover," Lee notes. "This retinol is encapsulated and is suitable for sensitive skintypes."
Shani Darden Texture Reform Gentle Resurfacing Serum ($95)
"I created Texture Reform for those with more sensitive skin," says Darden. "It features retinyl palmitate to boost cellular turnover, which will improve skin texture, and it works gradually, making it safe for sensitive skin. It also has lactic acid to gently exfoliate, aloe to soothe the skin, and niacinamide to improve skin tone."
Environ Youth Essentia Vita Peptide Eye Gel ($92)
"This eye gel has retinyl palmitate along with vitamins C and E to minimize the appearance of fine lines and boost hydration," Darden explains.
SkinMedica Age Defense Retinol Complex .25 ($62)
"MY FAV BY FAR," Hernandez raves. "This retinol is encapsulated in spheres of hyaluronic acid, making it gentle yet hydrating. It's formulated to time-release over eight hours, meaning it's penetrating more evenly into the skin, thus giving better results."
SkinCeuticals .50 Retinol ($76)
"This retinol is the next step up for someone who's been using a gentle retinol .25 or less and is ready to up their anti-aging game," says Hernandez.
Dr. Frances Prenna Jones Night Work ($175)
"Dr. Jones developedthis serum, and it's referred to as magic in a bottle," Hernandez shares. "It contains retinoic acid, vitamins, antioxidantsit's an essential all-in-one."
Tata Harper Retinoic Nutrient Face Oil With Vitamin A ($48)
"This clean nourishing face oil has 18 highly concentrated performance botanicals, vitamins, and minerals," Hernandez tells us. "It's gentle and restorative."
Paula's Choice Resist Intensive Wrinkle-Repair Retinol Serum ($42)
"I love this retinol serum because it's extremely gentle and packed with antioxidants and vitamin C," Hernandez says.
Next: Retinol Is Truly a Multipurpose IngredientHere's How to Use It
This article originally appeared on Who What Wear
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We Have Celeb Facialists on Speed DialThese Are the Retinol Serums They Love - Yahoo Lifestyle
Synthetic presentation of noncanonical Wnt5a motif promotes mechanosensing-dependent differentiation of stem cells and regeneration – Science Advances
By daniellenierenberg
INTRODUCTION
Human mesenchymal stem cells (hMSCs) have become increasingly popular as a cell source for repairing bone and other musculoskeletal tissues due to their availability, accessibility, and multipotency (1). The lineage commitment of hMSCs has been shown to be regulated by various signals, including mechanical stimuli, soluble factors, and cellextracellular matrix (ECM) interactions, in their natural niche microenvironment (2). Meanwhile, the delayed reunion of fractured bone remains a major clinical complication of surgery despite advances in operative techniques. The direct injection of stem cells into bone defects generally leads to limited stem cell grafting and differentiation due to the lack of necessary biochemical cues in the defect sites (3). Developing osteoinductive biomaterial scaffolds by incorporating developmentally relevant signaling cues to support and guide the differentiation of implanted stem cells in situ will enhance the clinical outcomes of stem cell therapies (4). For instance, scaffolds have been decorated with a wide range of bioactive motifs, including growth factors, bioactive peptides, and small molecules, to boost their osteoinductivity (5, 6). In recent years, biomimetic/bioactive peptides have become increasingly popular as inductive motifs for the biofunctionalization of biomaterials due to their major advantages, including their ease of immobilization onto various biomaterials via bioconjugation, better stability than proteins, and low cost (7). We previously demonstrated that the decoration of a hydrogel scaffold with an N-cadherin mimetic peptide promoted the chondrogenesis or the osteogenesis of hMSCs by emulating the enhanced intercellular interactions (8, 9). Therefore, there is an acute demand for previously unidentified osteoinductive ligands, which can potentially be identified by examining developmentally relevant proteinaceous cues (10).
Wnt signaling pathways have been reported to be essential to many developmental events, especially osteogenesis and bone formation (11, 12). The canonical Wnt signaling pathways generally involve the preservation and nuclear translocation of -catenin, which further triggers the activation of downstream genes to initiate osteogenic differentiation (13). On the other hand, the -cateninindependent noncanonical Wnt signaling cascade is activated by noncanonical Wnt ligands, such as Wnt5a (14). Wnt5a activation has been reported to contribute to the regeneration of multiple tissues, including the articular cartilage, the colonic crypt, and the liver, via paracrine or autocrine regulation (1517). During in vitro osteogenesis, embryonic stem cells express Wnt5a early on, rather than canonical Wnt3a, and cells expressing Wnt5a or treated with exogenous Wnt5a show a substantially enhanced osteogenic yield (18). In trabecular bone and bone marrow, Wnt5a is mainly expressed and secreted by osteoblastic niche cells, including precursor cells, osteoblasts, osteoclasts, and osteocytes (19). Wnt5a has been reported to preserve the proliferation and differentiation potential of stem cells in bone marrow and induce osteoblast maturation (20). Wnt5a signaling is a substantial constituent of bone morphogenetic protein 2mediated osteoblastogenesis (21). Collectively, these findings indicate that Wnt5a is an essential cue for the development of bones.
Wnt5a signaling is mediated through the Disheveled (Dvl) segment polarity proteindependent mechanism, which activates the small guanosine triphosphatase (GTPase) RhoA and its effector ROCKs (Rho-associated protein kinases) (22). RhoA-ROCK signaling plays a major regulatory role in the mechanotransduction signaling of cells by promoting focal adhesion formation (16), stress fiber assembly (23), and actomyosin contractility, and all these cellular events have been shown to enhance the osteogenesis of mesenchymal stem cells (MSCs). However, to the best of our knowledge, no prior studies have capitalized on the osteoinductive potential of noncanonical Wnt ligands to functionalize biomaterials or investigated the efficacy of such a developmental biologyinspired strategy to enhance the osteogenesis of MSCs and associated bone formation.
Recently, a Wnt5a mimetic hexapeptide, Foxy5 (formyl-Met-Asp-Gly-Cys-Glu-Leu), was shown to trigger cytosolic calcium signaling by activating -cateninindependent noncanonical Wnt signaling (24), and Foxy5 has recently been tested in a phase 1 clinical trial for treating cancer (www.clinicalTrials.gov; NCT02020291) (25). Here, we hypothesized that the functionalization of biomaterials with Foxy5 peptide can promote the mechanosensing and osteogenesis of hMSCs by activating noncanonical Wnt signaling (Fig. 1A). Our findings showed that this synthetic presentation of Wnt5a mimetic ligand activated noncanonical Wnt signaling, elevated the intracellular calcium, and promoted the mechanotransduction and osteogenesis of hMSCs, resulting in the enhanced bone regeneration in vivo. These findings emphasize the significance of the biofunctionalization of biomaterial scaffolds with developmentally guiding cues to enhance in situ tissue regeneration via grafted stem cells (26, 27).
(A) Porous, Foxy5 + RGD peptideconjugated MeHA hydrogels were developed by conjugating cysteine-containing functional peptides to MeHA molecules. (B) The porous scaffolds were used to copresent the adhesive ligand (RGD) and noncanonical Wnt5aactivating ligand (Foxy5) to synergistically induce the osteogenic lineage commitment of stem cells both in vitro and in vivo. (C) Rat MSC (rMSC)seeded hydrogels were used to fill calvarial defects for regeneration. (D) Micrographs of the 3D porous hydrogels with 200-m pores. The inset shows the microstructure of the MeHA porous hydrogel; scale bar, 50 m. (E) The Young modulus of the DTT-crosslinked MeHA hydrogels was verified using the Mach-1 mechanical tester. (F) The live/dead staining of the hMSCs seeded in the porous MeHA hydrogels showed the uniform distribution of the cells in the hydrogels. (G) Viable cell metabolic activity in the RGD, Foxy5 + RGD, and Scram + RGD hydrogels on day 7 of culture was characterized by alamarBlue assay. Data are shown as the means SD (n = 3).
To determine the effect of the Wnt5a mimetic peptide (Foxy5) on cellular behaviors, we grafted methacrylated hyaluronic acid (MeHA) with Foxy5 peptide (MDGECL, 1 mM) and arginylglycylaspartic acid (RGD) peptide (GCGYGRGDSPG, 1 mM) via Michael addition between the cysteine thiols of the peptide and the methacrylate groups of the MeHA (Fig. 1A and fig. S1). The peptide-functionalized MeHA (degree of methacryloyl substitution or methacrylation degree = 100 or 30%) (fig. S1) was then cross-linked to fabricate a three-dimensional (3D) porous hydrogel scaffold or a 2D hydrogel substrate for subsequent experiments (Foxy5 + RGD) (Fig. 1, B to D). Control hydrogels were fabricated with either RGD peptide alone (RGD) or the combination of scramble-sequenced Foxy5 peptide and RGD (GEMDCL, 1 mM, Scram + RGD). The RGD peptide was included in all groups to promote cell adhesion. The average Young moduli of the hydrogels from the RGD, Foxy5 + RGD, and Scram + RGD groups were determined to be 11.26, 10.82, and 10.96 kPa, respectively, indicating similar hydrogel stiffness in all groups (Fig. 1E). The storage moduli and loss moduli acquired from the frequency sweep analysis were not significantly different among the RGD, Foxy5 + RGD, and Scram + RGD groups (fig. S2A). Similarly, the surface roughness and the stiffness of 2D ultraviolet (UV)cross-linked hydrogels are not significantly different (fig. S2B). Our previous experience shows that the photocrosslinked MeHA hydrogels are typically stiffer than the dithiothreitol (DTT)cross-linked MeHA hydrogels given the same macromer content and methacrylation degree. This can be due to the semirigid nature of hyaluronic acid (HA) backbone, which may hinder the efficient crosslinking of HA-grafted methacryloyl groups by bifunctional crosslinkers (e.g., DTT). Therefore, by using the MeHA with the lower (30%) methacrylation degree to fabricate 2D hydrogels, the average Young moduli of the photocrosslinked hydrogels with 667 s of UV radiation were not significantly different from those of the DTTcross-linked MeHA hydrogels (100% methacrylation degree) (fig. S2, C and D). We believe that the results acquired from the 2D hydrogel substrates are representative and comparable with the data obtained from the 3D macroporous hydrogels. The 3D porous hydrogels used in this work have large pore sizes of around a few hundred micrometers, which are significantly larger than that of cells. The cells seeded in these 3D hydrogels are essentially still residing on top of the curved surfaces of the pores and are interacting with a more 2D-like rather than 3D microenvironment, and this is similar to the lining of osteoblasts on the surface of porous trabecular bone.
To evaluate the cytocompatibility of the peptide-functionalized hydrogels, we seeded hMSCs into the porous hydrogel constructs and allowed them to adhere for 4 hours, followed by further culture in basal growth media for another 7 days. Live/dead staining after 7 days of culture revealed that the majority of the seeded stem cells were viable and uniformly adhered to the RGD, Foxy5 + RGD, and Scram + RGD porous hydrogels (Fig. 1F). The alamarBlue assay showed that the seeded cells in all groups maintained consistent and robust metabolic activity in the porous hydrogel scaffolds for 7 days (Fig. 1G). These results indicate that the conjugated bioactive Foxy5 peptide was noncytotoxic, consistent with previous reports (24).
To further investigate the molecular events mediated by the noncanonical Wnt5a mimetic Foxy5 peptide, we used immunofluorescence staining to examine the expression levels of integrin V, integrin 1, phosphorylated focal adhesion kinase (p-FAK), and ROCK2 (fig. S3), which are essential elements for mediating mechanotransduction and have been reported to promote the osteogenic differentiation of stem cells. The staining intensities of integrin V and integrin 1 in the hMSCs cultured in the Foxy5 + RGD group appeared slightly higher but were not statistically different compared with that in the RGD and Scram + RGD groups (fig. S3, A and B). The staining intensity of p-FAK in the Foxy5 + RGD group was 92 and 33% higher than those in the RGD and Scram + RGD groups, respectively (fig. S3C). Consistent with the elevated expression of focal adhesion complex components, the Foxy5 + RGD group also showed ROCK2 staining intensity 135 and 34% higher than those in the RGD and Scram + RGD groups, respectively, after 7 days of osteogenic culture (fig. S3D). This enhanced expression of p-FAK and ROCK2 supports our speculation that the Foxy5 peptide presented by the biomaterial facilitates the mechanotransduction of the cells by activating noncanonical Wnt signaling to up-regulate the expression of focal adhesion complex molecules (p-FAK) and mechanotransduction signaling molecules (ROCK2).
We next explored the molecular signaling events by which the presentation of Foxy5 peptide via the hydrogel scaffold increased the mechanotransduction and consequent osteogenic lineage commitment of hMSCs (Fig. 2A). Noncanonical Wnt5a signaling has been shown to regulate the signaling of the Rho family of GTPases, such as RhoA, and studies have shown that RhoA is essential for actin cytoskeletal stability and associated actomyosin contractility via its downstream effectors, including ROCKs (22). Therefore, to examine the contribution of RhoA signaling and actomyosin contractility to the osteogenic effect of Foxy5 peptide presentation, we added Y-27632, an inhibitor of ROCKs, and blebbistatin, an inhibitor of nonmuscle myosin II (NMII), to the media in the Foxy5 + RGD group during the 7 days of osteogenic culture. The inhibition of ROCK with Y-27632 completely abolished the up-regulated osteogenic gene expression in the Foxy5 + RGD hydrogels. Blocking NMII activity also led to significantly down-regulated expression of the osteogenic genes alkaline phosphatase (ALP), type I collagen, and osteopontin (OPN) compared with the corresponding levels in the RGD group (fig. S4). Specifically, after 7 days of osteogenic culture, the expression levels of type I collagen, ALP, RUNX2, and OPN in the Y-27632Foxy5 + RGD group were down-regulated by 80.20, 97.96, 71.10, and 97.70%, respectively, compared with those in the Foxy5 + RGD group. The expression levels of type I collagen, ALP, RUNX2, and OPN in the blebbistatinFoxy5 + RGD group were down-regulated by 86.23, 98.54, 24.24, and 87.48%, respectively, compared with those in the Foxy5 + RGD group. These findings suggest that the pro-osteogenic effect of the Foxy5 peptide presentation can be attributed to the activation of RhoA signaling and associated actomyosin contractility.
(A) Schematic illustration of the seeding of hMSCs on the Foxy5/Scram + RGD peptidefunctionalized 2D hydrogel substrate. (B) Gene expression level of the RhoA signaling cascade (Wnt5a coreceptor Dvl2, RhoA, ROCK), downstream mechano-effector (NMII), and major focal adhesion adaptor protein (vinculin) in hMSCs in 3D porous hydrogels conjugated with RGD peptide alone (RGD), Foxy5 and RGD peptide (Foxy5 + RGD), or scrambled Foxy5 peptide and RGD peptide (Scram + RGD), respectively, after 7 days of osteogenic culture (n = 9). (C) Representative micrographs of fluorescence staining for F-actin (red), nuclei (blue), and RhoA (green) in hMSCs cultured on the 2D RGD, Foxy5 + RGD, and Scram + RGD hydrogels. Quantification showed a significantly higher RhoA staining intensity in the Foxy5 + RGD group than in the RGD and Scram + RGD groups (n = 20). a.u., arbitrary units. (D) Western blot bands and quantification of the expression level of mechano-responsive kinases ROCK2 and p-FAK (phosphorylated at the Ser722 sites) in each group (RGD, Foxy5 + RGD, Scram + RGD). (E) Representative merged fluorescence and bright-field micrographs of intracellular calcium in hMSCs cultured on RGD, Foxy5 + RGD, and Scram + RGD 2D hydrogels (stained with Fura-AM). (F) Quantification showed a significantly higher intracellular calcium level in the Foxy5 + RGD group than in the RGD and Scram + RGD groups. Scale bars, 50 m. Data are shown as the means SD (n = 9). Statistical significance: *P < 0.05, **P < 0.01, and ***P < 0.001.
We further investigated the mechanism underlying the enhanced RhoA signaling and actomyosin contractility via Foxy5 peptidemediated noncanonical Wnt signaling. Gene expression analyses revealed the up-regulated expression of Dvl2, RhoA, ROCK2, vinculin, and NMII in the presence of conjugated Foxy5 peptides after 7 days of osteogenic culture (Fig. 2B). Specifically, the Foxy5 + RGD group showed Dvl2, RhoA, ROCK2, vinculin, and NMII expression levels that were increased by 43, 27, 65, 72, and 24%, respectively, compared with those in the RGD group. Meanwhile, the expression of ROCK1, which was speculated to contribute to F-actin instability, was down-regulated by 25% in the Foxy5 + RGD group compared with that in the RGD group. Furthermore, the expression of the canonical Wnt signalingrelated genes (Wnt3a, Frizzled 3, LRP5, LRP6, and -catenin) was significantly up-regulated in the Foxy5 + RGD group compared with that in the control groups (fig. S5), and this is consistent with a previous report showing that the activated noncanonical Wnt signaling up-regulated the expression of canonical Wnt signaling factors during osteoblastogenesis (28). The expression of these mechanotransduction-related genes and canonical Wnt signalingrelated genes in the Scram + RGD group was not significantly different from that in the RGD group (Fig. 2B and fig. S5). We further quantified the expression of RhoA, ROCK2, and p-FAK based on immunofluorescence staining and Western blot analysis. The Foxy5 + RGD hydrogels showed RhoA staining intensity 92 and 134% higher than that in the RGD group and Scram + RGD groups, respectively, after 7 days of osteogenic culture (Fig. 2C). Further analysis showed a significantly increased cytoplasmic distribution of RhoA, consistent with the more prominent F-actin cytoskeleton, in cells cultured on hydrogels conjugated with Foxy5 peptide compared with those cultured on the controls. The Western blotting results showed that the expression levels of ROCK2 and p-FAK, two key mechanotransduction signaling molecules, were significantly up-regulated in the Foxy5 + RGD hydrogels (Fig. 2D) by 83 and 75% compared with those in the RGD hydrogels, respectively, and by 39 and 35% compared with those in the Scram + RGD hydrogels, respectively (Fig. 2E). Together, these data suggest that Foxy5 peptide immobilized on hydrogels is capable of initiating noncanonical Wnt signaling via the up-regulation of Dvl2, which further activates downstream RhoA signaling, leading to enhanced F-actin stability, actomyosin contractility, and cell adhesion structure development. Furthermore, the canonical Wnt signaling has been shown to promote the osteogenesis of hMSCs directly through the up-regulation of -catenin and downstream osteogenic genes including RUNX2, Dlx5, and Osterix (29). The immobilized Foxy5 peptide may indirectly facilitate the canonical Wnt signaling via the up-regulation of Frizzled3, LRP5/6, and -catenin. More thorough examinations on the effect of Wnt5a mimetic ligands on both canonical and noncanonical Wnt signaling are certainly worthy of further investigations in the future.
Our data reveal that the Foxy5 peptidemediated activation of noncanonical Wnt signaling is essential for regulating the expression and localization of critical signaling molecules involved in cell adhesion and mechanotransduction, including YAP, ROCK2, and p-FAK, which are essential for the osteogenesis of MSCs. The subtypes of ROCK, ROCK1, and ROCK2 have been shown to play distinct roles in regulating cytoskeletal tension. ROCK1 is a nonsecreted protein that destabilizes the actin cytoskeleton by regulating myosin light chain phosphorylation and peripheral actomyosin contraction, whereas ROCK2 is required for stabilizing the actin cytoskeleton by regulating cofilin phosphorylation (30). Previous studies have revealed that ROCK2 activity is effectively activated upon Wnt5a ligation to its receptors (22). We observed the up-regulation of ROCK2 expression and the down-regulation of ROCK1 expression, along with a significant increase in the focal adhesion levels in the MSCs presented with hydrogel-conjugated Foxy5 peptide. Therefore, the elevated ROCK2 activity results in enhanced cytoskeletal stability and more robust mechanotransduction signaling, both of which contribute to enhanced osteogenesis. When we inhibited ROCK activity in the Y-27632Foxy5 + RGD group using 10 M Y-27632, the expression of osteogenic genes was greatly reduced, thereby further confirming the important role of ROCK2 in Foxy5 peptideinduced osteogenesis.
Apart from RhoA activation, noncanonical Wnt5a activation has also been reported to lead to the mobilization of free intracellular calcium, which regulates multiple cellular behaviors, including the motility and differentiation of MSCs (31). To test the effect of Foxy5 peptide on the intracellular calcium level, we subjected hMSCs to Furaacetoxymethyl (AM) staining after being seeded on 2D peptide-conjugated MeHA hydrogels and cultured in osteogenic media. After 7 days of osteogenic culture, Fura-AM staining showed that cells on Foxy5 + RGD hydrogels exhibited 122 and 127% higher fluorescence intensity than those on RGD and Scram + RGD hydrogels, respectively (Fig. 2F). This finding suggests that the conjugated Foxy5 peptide is capable of activating noncanonical Wnt signaling to elevate the intracellular calcium level of MSCs, promoting osteogenesis.
Calcium-dependent noncanonical Wnt signaling pathways are known to participate in osteoblast differentiation, maturation, and bone formation (31, 32). Intracellular Ca2+ and calcium-binding/activatable signaling factors (calmodulin, calmodulin kinase II, calcineurin, etc.) are critical to the growth and differentiation of osteoblasts (33). Our biochemistry analysis and histological staining further showed that the amount of bone ECM production by hMSCs was significantly enhanced together with the intracellular calcium concentration in the hydrogels conjugated with the Foxy5 peptide, and this indicates that the elevated intracellular calcium level contributes to the enhanced osteogenesis of MSCs seeded in Foxy5 peptidefunctionalized hydrogels.
The guided lineage commitment of stem cells is a critical prerequisite for successful and efficient tissue regeneration, which is known to be modulated by the concerted actions of multiple microenvironmental signals (34). We next examined whether the hydrogels functionalized with the Wnt5a mimetic peptide could promote the osteogenic differentiation of hMSCs. We cultured hMSCs on 2D hydrogel substrates that were functionalized with RGD alone (RGD) or RGD with either Foxy5 peptide (Foxy5 + RGD) or scrambled Foxy5 peptide (Scram + RGD) in osteogenic induction media. Supplementation of the culture media with nonconjugated soluble Foxy5 peptide was previously reported to affect the chemotaxis of cancer cells (35). To compare the effects of the freely diffusing soluble form and the hydrogel-immobilized form of Foxy5 peptide on hMSCs, we included two control groups in which the osteogenic medium was supplemented with soluble, free, nonconjugated Foxy5 or scrambled Foxy5 peptide (free Foxy5 and free Scram) in the same amounts as those present in the conjugated hydrogels (Foxy5 + RGD and Scram + RGD).
Previous studies have demonstrated the critical role of YAP/TAZ-mediated mechanotransduction signaling in osteogenesis (36). We performed immunofluorescence staining for YAP and RUNX2 after 7 days of osteogenic culture. The hMSCs cultured on Foxy5 + RGD hydrogels consistently exhibited more YAP nuclear localization than those in all other control groups on 2D hydrogels (Fig. 3A). Specifically, quantification of the average nuclear-to-cytoplasmic staining intensity ratio (N/C ratio) of YAP in at least 20 representative cells from each group showed that the YAP nuclear localization in the Foxy5 + RGD group was 134 and 88% higher than that in the RGD and Scram + RGD groups, respectively (Fig. 3, A and D). Moreover, the addition of soluble Foxy5 peptide in the culture media (free Foxy5) failed to significantly increase the YAP nuclear localization as much as the hydrogel-conjugated Foxy5 peptide (only a 53% increase compared with the RGD group), whereas the free, soluble scrambled peptide had no significant effect (Fig. 3, A and C). This finding indicates that the hydrogel-conjugated Foxy5 peptide has significantly higher bioactivity than the unconjugated Wnt5a peptide directly added to the media in terms of promoting mechanosensing and osteogenesis. The immobilization of this ligand on the porous scaffold greatly enhanced the local effective concentration in the microenvironment of hMSCs, thereby facilitating the ligation of Wnt5a ligands to the receptors on the cell membrane. In contrast, the direct supplementation of the ligand resulted in its dilution in the entire volume of the media and therefore reduced the local effective ligand concentration. We also speculated that the immobilized ligands are unlikely to be internalized by cells upon ligation to membranous receptors, whereas the free ligands can be quickly internalized by cells and lose their activation function (37).
(A) Fluorescence micrographs of hMSCs stained for F-actin (red), nuclei (blue), and the mechanosensing marker YAP (green) or the osteogenic marker RUNX2 (green) (B) and ALP (blue in bright-field) (C), cultured on the RGD, Foxy5 + RGD, and Scram + RGD hydrogels. (D) Analysis of the nuclear localization of YAP determined by the nuclear-to-cytoplasmic fluorescence intensity ratio (N/C ratio) (n = 20) and (E) RUNX2 nuclear localization (n = 20) and (F) ALP expression of representative cells cultured on 2D hydrogels in the different experimental groups (n = 9). Scale bars represent 50 m in the fluorescence micrographs and 200 m in the bright-field images. Data are shown as the means SD. Statistical significance: *P < 0.05, **P < 0.01, and ***P < 0.001 significant difference.
To examine the effect of YAP nuclear accumulation on the osteogenesis of hMSCs, we analyzed the early osteogenic lineage commitment by immunofluorescence staining for RUNX2, an essential osteogenic transcription factor, after 7 days of osteoinductive culture. Cells in the Foxy5 + RGD group showed RUNX2 nuclear-to-cytoplasmic ratio 97 and 116% greater than that in the RGD and Scram + RGD groups, consistent with the YAP nuclear localization results (Fig. 3, B and E). In contrast, the expression levels of RUNX2 in the free Foxy5 and free Scram groups were only slightly higher than those in the RGD group. Furthermore, staining for ALP, another key osteogenesis marker, showed that the average percentage of ALP-positive cells in the Foxy5 + RGD group was 55, 52, 94, and 77% higher than that in the RGD, Scram + RGD, free Foxy5, and free Scram groups, respectively (Fig. 3, C and F). These findings indicate that hydrogel-conjugated Foxy5 peptide promotes the mechanosensing-dependent osteogenic differentiation of hMSCs and that the immobilization of Foxy5 peptide on hydrogels is more effective than the continuous supplementation of media with soluble Foxy5 peptide to enhance the osteogenesis of hMSCs. To further examine the effectiveness of the immobilized Foxy5 peptide on the substrates with different stiffness, we analyzed the mechanosensing and the early osteogenic lineage commitment by immunofluorescence staining for YAP and RUNX2 on the 2D MeHA hydrogels with varying stiffness of 2, 5, and 14 kPa (38). Cells in the Foxy5 + RGD group showed significantly higher YAP and RUNX2 nuclear-to-cytoplasmic ratio than that in the RGD and Scram + RGD groups at each of the selected hydrogel stiffness levels (fig. S6). This indicates that the biomaterial-conjugated Foxy5 peptide promotes osteogenesis in a wide range of substrate stiffness, and we found that the pro-osteogenic effect of the conjugated Foxy5 peptide is more significant at low substrate stiffness (2 kPa) (fig. S6).
We next examined the effect of Foxy5 peptide conjugated to 3D porous hydrogels on the osteogenic differentiation of seeded hMSCs from three different donors after 7 days (Fig. 4, A and B, fig. S7A, and tables S1 and S2) and 14 days (fig. S7B) of osteogenic culture. The real-time quantitative polymerase chain reaction (RT-qPCR) data showed that the expression levels of type I collagen, ALP, RUNX2, and OPN in cells seeded in the Foxy5 peptidefunctionalized porous hydrogels (Foxy5 + RGD group) were up-regulated by 33, 57, 35, and 422%, respectively, compared with those in cells seeded in the hydrogels without Foxy5 functionalization (RGD group) (Fig. 4B) after 7 days of osteogenic culture. In contrast, presentation of the nonfunctional scrambled peptide (Scram + RGD group) had no significant influence on the expression levels of these osteogenic genes compared with corresponding levels in the RGD group. The pro-osteogenic effect of the conjugated Foxy5 peptide diminished after 14 days of culture (fig. S7B). The diminishing effect of Foxy5 peptide can be attributed to the decreasing membrane presence of available LRP5/6 in the osteogenically differentiating hMSCs (39, 40). In addition, the increasing extracellular matrix that accumulated around hMSCs over time may have also contributed to the effect of conjugated Foxy5 peptide. It is noteworthy that the declining expression of Wnt receptors and Wnt signaling are essential for the formation of mineralized matrix (39). Therefore, this diminished effect of Foxy5 peptide over time may be beneficial to the osteogenesis of seeded hMSCs and subsequent neobone formation. Consistent with the gene expression data, both Alizarin Red and von Kossa staining revealed more substantial calcification in the Foxy5 + RGD group than in the other control groups. Quantitative analysis showed that the Alizarin Red and von Kossa staining intensities in the Foxy5 + RGD group were 262 and 107% higher than those in the RGD groups after 14 days of culture, respectively (Fig. 4, C and D). Furthermore, we assessed the organic bone matrix synthesis of stem cells by type I collagen staining. The Foxy5 + RGD group exhibited 163 and 179% higher type I collagen staining than the RGD and Scram + RGD groups, respectively (Fig. 4, C and D). These findings suggest that Foxy5 conjugated to the 3D porous hydrogel scaffold significantly promotes the expression of both early- and late-stage osteogenic genes in hMSCs and inorganic/organic bone matrix synthesis.
(A) Schematic illustration of the seeding of hMSCs in the Foxy5/Scram + RGD peptidefunctionalized 3D hydrogel scaffolds. (B) Quantitative gene expression of osteogenic markers (type I collagen, RUNX2, ALP, and OPN) in hMSCs seeded in porous hydrogels conjugated with RGD peptide alone (RGD), Foxy5 and RGD peptides (Foxy5 + RGD), or Scram and RGD peptides (Scram + RGD) in osteogenic culture. (C) von Kossa staining, Alizarin Red S staining, and immunohistochemistry staining of type I collagen and (D) quantification of the staining intensities after 14 days of osteogenic culture. Scale bars, 50 m. Data are shown as the means SD (n = 9). Statistical significance: * P < 0.05, **P < 0.01, and ***P < 0.001.
In mature bone tissues, the unique osteoblastic microenvironment niche provides MSCs with the necessary biological cues, including stromal cellderived factor 1, angiopoietin 1, and OPN, derived from osteoblasts, osteoclasts, osteocytes, and endothelial cells in trabecular bone and bone marrow (19, 41). Many previous studies have reported the regulation of MSC signaling and lineage commitment by systemic hormones or localized growth factors (42). Fu et al. demonstrated that Wnt3a-mediated canonical Wnt signaling activation antagonizes the terminal osteogenic differentiation of MSCs, while Wnt5a-mediated noncanonical Wnt signaling mitigates the inhibitory effect of Wnt3a. In the natural osteoblastic niche, Wnt5a proteins are secreted by the surrounding tissues and bind to the Frizzled/Ror2 surface Wnt receptors of hMSCs via paracrine mechanisms (43). We used porous hydrogels functionalized with Wnt5a mimetic Foxy5 peptide to emulate this pro-osteogenic niche and promote the osteogenesis of hMSCs. In addition to Foxy5 peptide, RGD peptide was also conjugated to all hydrogels to provide adhesive motifs for the hMSCs because Foxy5 peptide alone cannot support effective cell adhesion. The promechanotransduction and pro-osteogenic effects of Foxy5 peptide were therefore not studied in the absence of RGD peptides, which is a limitation of the study. Nevertheless, integrin ligands are important components of the natural osteogenic niche in bones. The potential crosstalk between integrin signaling and Wnt signaling and the associated effects on stem cell differentiation certainly warrant further investigation.
We further evaluated the efficacy of the Foxy5 peptide conjugated to the hydrogel in assisting in vivo bone regeneration in rat calvarial defects. Rat MSCs (rMSCs) with trilineage differentiation potential (4446) were first seeded in porous hydrogels functionalized with RGD, Foxy5 + RGD, or Scram + RGD peptides and cultured in osteogenic media for 7 days prior to transplantation into the defects (Fig. 5A). The RT-qPCR data showed that the expression levels of type I collagen, ALP, RUNX2, OPN, Dvl2, RhoA, and vinculin in rMSCs of the Foxy5 + RGD group were all significantly higher compared with those in the control groups (RGD group, Scram + RGD) after 7 days of osteogenic culture (fig. S8, A and B). Eight weeks after transplantation, both hematoxylin and eosin (H&E) staining and immunohistochemical staining for osteocalcin and type I collagen revealed enhanced osteoblastic marker expression and bone matrix formation in the Foxy5 + RGD group compared with the RGD, Scram + RGD, and blank groups (Fig. 5B). The average staining intensity for osteocalcin was 124, 114, and 240% higher and that of type I collagen was 105, 104, and 144% higher in the Foxy5 + RGD group than in the blank, RGD, and Scram + RGD groups, respectively (Fig. 5D). The average staining intensity for osteocalcin and type I collagen in the Foxy5 + RGD group was still around 30% lower than that in the native calvarial tissue (Fig. 5D). Furthermore, the microcomputed tomography (micro-CT) reconstruction data revealed considerably more new bone formation in the defects treated with hydrogels conjugated with Foxy5 and RGD peptides (Foxy5 + RGD group) than in those treated with the control hydrogels (blank, RGD, and Scram + RGD groups) (Fig. 5C). Quantitative analysis showed that the bone volumetototal tissue volume (BV/TV) ratio in the Foxy5 + RGD group was 107, 57, and 198% higher than that in the RGD, Scram + RGD, and sham blank groups, respectively. Notably, the average BV/TV ratio of healthy calvarial bone was determined to be 35.25% due to other skeletal components, such as fibrous connective tissues. The average BV/TV ratio in the Foxy5 + RGD group was 25.19%, suggesting a substantial recovery of approximately 71.49% of the healthy calvarial bone volume. These findings demonstrate that the functionalization of biomaterial scaffolds with this Wnt5a mimetic peptide can substantially enhance bone regeneration in vivo. No significant abnormalities in tissue structure or morphology were observed around the implantation site. We believe that the restricted bioactivity of the mimetic peptide (compared with that of the parent protein) and the immobilization of this Wnt5a ligand on the biomaterial for local implantation will limit potential undesired nonspecific actions that may arise due to peptide transportation to other off-target sites (47).
(A) Schematic illustration of the implantation of rMSC-seeded and peptide-functionalized porous hydrogels in rat calvarial defects. (B) H&E staining and immunohistochemical staining of the native healthy bone tissue and the calvarial defects treated with the RGD hydrogels, Foxy5 + RGD hydrogels, Scram + RGD hydrogels, and no hydrogels (blank) 8 weeks after implantation (n = 3). High-magnification images showing the defect/native bone boundaries highlighted in yellow and red boxes and defect center areas in blue boxes in the low-magnification images of H&E-stained sections. The dotted lines indicate the boundary between the defect and native bone. The newly formed bone was seamlessly integrated with the neighboring native bone in the Foxy5 + RGD group. Scale bars, 50 m. (C) Top view of 3D micro-CT images showing calvarial bone defects after 8 weeks in all groups (n = 3). (D) Bone volume (normalized to total tissue volume, BV/TV) in the calvarial defects in all groups after 8 weeks (n = 3). The bone volume of healthy rat calvarial bone is shown as the benchmark. Quantification of the immunohistochemical staining intensity of the osteogenic markers, including osteocalcin and type I collagen, showing the higher intensity in the Foxy5 + RGD group compared with those of the RGD and Scram + RGD control groups. Data are shown as the means SD (n = 9). Statistical significance: *P < 0.05, **P < 0.01, and ***P < 0.001 significant difference.
MeHA macromolecules were synthesized from sodium hyaluronate powder (molecular weight, ~74 kDa; Lifecore, Chaska, Minnesota, USA), as previously reported (8). Briefly, 100 ml of 1% (w/v) sodium hyaluronate solution was reacted for 24 hours with 4 or 1.5 ml of methacrylic anhydride at pH 9.5, adjusted with 2 M NaOH solution. After complete dialysis and lyophilization, 100% methacrylation or 30% methacrylation was confirmed using proton nuclear magnetic resonance (1H NMR). The RGD peptide (GCGYGRGDSPG) and Foxy5 peptide (MDGCEL) (GenScript, Nanjing, Jiangsu, China) with a cysteine amino acid at the C-terminal end were conjugated to the MeHA backbone with a Michael addition reaction between the methacrylate groups and the thiol groups of each peptide in basic phosphate buffer (pH 8.0) containing 10 M tris(2-carboxyethyl)phosphine at 37C. The molar ratio of methacrylate to each peptide thiol was 100:3. RGD-functionalized, Foxy5-conjugated porous MeHA hydrogels were fabricated from 50 l of the peptide-conjugated MeHA solution (3% w/v, 100% methacrylation) after 2 hours, with 1.51 mol of DTT as the cross-linker to consume all residual methacrylic groups, in round polyvinyl chloride molds fully packed with a poly(methyl methacrylate) (PMMA) microsphere porogen ( 200 m). The constructs generated were immersed in acetone and shaken at 90 rpm to dissolve the PMMA porogen, sterilized with 75% ethanol for 1 day, and rinsed three times with sterile phosphate-buffered saline (PBS). In the directly Foxy5 peptidesupplemented MeHA (free Foxy5) group and the directly scrambled peptidesupplemented MeHA (free Scram) group, we only used the same Foxy5 + RGDfunctionalized MeHA solution or Scram + RGDfunctionalized MeHA solution (3% w/v, 100% methacrylation) to fabricate the porous hydrogels, respectively.
We used MeHA with 30% methacrylation supplemented with 0.05% (w/v) photoinitiator I2959 (Sigma-Aldrich, MO, USA) to make Foxy5 + RGDfunctionalized MeHA solution, Scram + RGDfunctionalized MeHA solution, or RGD-functionalized MeHA solution (3% w/v, 30% methacrylation) and to fabricate 2D hydrogels with different stiffness in polyvinyl chloride molds under 367, 467, 667, or 1067 seconds of UV exposure. All 2D hydrogels were sterilized before cell culture. The surface roughness and modulus were determined by atomic force microscopy (Bruker, MA, USA).
2D-biofunctionalized substrates were fabricated by polymerizing peptide-conjugated MeHA precursor solutions (3% w/v, 30% methacrylation) under UV light (wavelength, 365 nm; intensity, 7 mW/cm2) on methacrylated glass coverslips. The porous MeHA hydrogel constructs (height, ~1.5 mm; 1 mm) were polymerized in molds filled with 200-m PMMA microbeads to form an interconnected porous structure for in vitro experiments and for in vivo calvarial defect regeneration (Fig. 1, B and C) (9). Homogenous, interconnected spherical structures within the hydrogels were characterized through bright-field images captured using a fluorescence microscope (Nikon, Japan) (Fig. 1D). The Young moduli of the hydrogels were determined using a mechanical tester (Mach-1, Biomomentum Inc., Suite, Canada), and the strain-controlled frequency sweep mechanical tests were performed using a rheometer (Malvern Inc., Malvern, Britain).
Passage-4 hMSCs (Lonza, Walkersville, Maryland, USA) were expanded in basal growth medium [-minimal essential medium (MEM) supplemented with 16.7% (v/v) fetal bovine serum (FBS), penicillin-streptomycin (P/S; 100 U ml1), and 2 mM l-glutamine]. Growth medium (50 l) containing 5 105 hMSCs (108 cells ml1) was injected into one semidry, porous MeHA-RGD hydrogel, which was incubated at 37C for 4 hours to allow cell attachment to the hydrogels. Then, 1 ml of osteogenic medium [-MEM, 16.67% FBS, 1% P/S, 2 mM l-glutamine, 10 mM -glycerophosphate disodium, l-ascorbic acid 2-phosphate (50 mg ml1), and 100 nM dexamethasone] was added to all the hydrogels, and the medium was changed every 2 days. In the control group, Foxy5 peptide or scrambled peptide solution was added directly to the hydrogels at the beginning of osteogenic culture. Samples were collected on days 7 and 14 to evaluate the degree of osteogenesis by traditional qPCR and immunofluorescence staining. Cell viability was determined by alamarBlue assay (Invitrogen, Carlsbad, California, USA) after 7 days in osteogenic culture. Live/dead staining was performed by adding 3 M calcein AM and 3 M propidium iodide (Thermo Fisher Scientific, Waltham, Massachusetts, USA) to the hydrogels. After incubation for 30 min at 37C, the hydrogels were washed three times with PBS, and fluorescence images were captured using a confocal microscope (Nikon C2, Tokyo, Japan). The quantification of immunofluorescence staining results was conducted by using the ImageJ software [National Institutes of Health (NIH), Baltimore, Maryland, USA]. First, we adjusted the color images of the immunofluorescence staining to the 8-bit grayscale images, and then we selected the region of cells that best represent the overall staining intensity of the samples in the immunofluorescence staining results. The average grayscale values of the region of interest taken from at least 20 cells in each group were determined and compared to get the quantification results. The reported data of biochemical assays are the pooled results from three experiments.
All samples were homogenized in 1 ml of TRIzol reagent (Invitrogen), and total RNA was extracted according to the manufacturers protocol. The RNA concentration was measured using a NanoDrop One spectrophotometer (NanoDrop Technologies, Waltham, Massachusetts, USA). Total RNA (1 g) was reverse transcribed into cDNA using the RevertAid First Strand cDNA Synthesis Kit (Thermo Fisher Scientific). qPCR was performed on an Applied Biosystems StepOnePlus Real-Time PCR System with TaqMan primers and probes (Applied Biosciences, Waltham, Massachusetts, USA) specific for glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and other osteogenic genes, including those encoding RUNX2, ALP, and type I collagen. The sequences of the TaqMan primers and probes used are listed in table S2. The osteogenic gene expression levels were normalized to that of GAPDH, and the relative expression levels were calculated with the 2Ct method.
Hydrogel samples were fixed overnight in 4% paraformaldehyde at 4C, dehydrated in a graded series of ethanol, crystalized in a graded series of xylene, and embedded in paraffin. Histological sections (7 m) were stained for type I collagen using the VECTASTAIN ABC Kit and the DAB Substrate Kit (Vector Laboratories, Burlingame, California, USA). Briefly, hyaluronidase (0.5 g liter1) was applied to the rehydrated samples to predigest them at 37C for 30 min. The samples were then incubated with 0.5 N acetic acid for 4 hours at 4C to induce swelling, followed by incubation at 4C overnight with a primary antibody directed against type I collagen (antitype I collagen, diluted 1:200; sc-59772, Santa Cruz Biotechnology). Immunofluorescence staining for the osteogenic-related proteins (YAP and RUNX2) and cellular contractionrelated proteins (RhoA) was conducted as previously reported (9). The calcification of phosphates and calcium ions was identified with von Kossa staining and Alizarin Red S staining, respectively. Briefly, von Kossa stain was applied to the rehydrated sections, as previously reported. To stain with Alizarin Red S, 1 ml of 0.5% (w/v) Alizarin Red S solution (Sigma) was applied to each hydrogel sample; the samples were then incubated for 5 min at room temperature before being washed, dehydrated, cleared, and sealed. Images were captured using a bright-field microscope (Nikon). The quantification was conducted by using the ImageJ software (NIH). First, we adjusted the color images of immunohistochemistry (IHC) staining to the 8-bit grayscale images, and then we selected regions of interests of identical size that best represent the overall staining intensity of the samples in the IHC staining results. The average grayscale values of the region of interest taken from three parallel samples in each group were determined and compared to get the quantification results. The reported data of biochemical assays are pooled results from three experiments.
Strictly following the guidelines of the Institutional Animal Care and Use Committee at The Chinese University of Hong Kong, 12-week-old male Sprague-Dawley rats were randomly divided into four groups, shaved, and prepped for aseptic surgery. A midline skin flap was raised over the parietal bones and reflected caudally to expose the midsagittal and transverse sutures. The periosteum was incised along the midsagittal suture and the right or left transverse suture and removed to expose the parietal bone. A 5-mm-diameter defect was created using a trephine with normal saline irrigation during processing, and a section of the bone was removed to expose the dura mater. 3D porous peptidefunctionalized HA hydrogels (n = 3 per group) 5 mm in diameter and 1 mm thick were seeded with 1 million rMSCs with trilineage differentiation potential (46). After 7 days of in vitro osteogenic induction in the incubator, the hydrogels were implanted into the calvarial defects. All experimental animals were maintained until 8 weeks from the day of defect creation. After the rats were euthanized, the parietal bones were harvested and decalcified with 10% EDTA solution. The subsequent H&E staining and histological analysis were performed as described in previous publications (9).
All data are presented as the means SD. Statistica (Statsoft, Tulsa, Oklahoma, USA) was used to perform the statistical analyses using two-way analysis variance (ANOVA) and Tukeys honest significant difference post hoc test of the means; the culture period and experimental groups were used as independent variables.
Acknowledgments: We are grateful for the technical support from J. Lai, S. Wong, and A. Cheung from the School of Biomedical Sciences (The Chinese University of Hong Kong). We thank M. Zhu and K. Zhang for proofreading the manuscript. We sincerely thank M. Wong, N. So, K. Wei, M. Zhu, B. Yang, H. Chen, K. Zou, K. Zhang, Y. Jing, D. Siu Hong Wong, X. Xu, E. Yingrui Deng, X. Chen, and W. Li for the valuable discussions, support, and love. Funding: Project 31570979 is supported by the National Natural Science Foundation of China. The work described in this paper is supported by a General Research Fund grant from the Research Grants Council of Hong Kong (project nos. 14202215 and 14220716). This research is also supported by project BME-p3-15 of the Shun Hing Institute of Advanced Engineering (The Chinese University of Hong Kong). This work is supported by the Health and Medical Research Fund, the Food and Health Bureau, the Government of the Hong Kong Special Administrative Region (reference no. 04152836). This research is supported by the Chow Yuk Ho Technology Centre for Innovative Medicine (The Chinese University of Hong Kong). The work was partially supported by the Hong Kong Research Grants Council Theme-based Research Scheme (reference no. T13-402/17-N, Functional Bone Regeneration in Challenging Bone Disorders and Defects, 1 November 2017 to 31 October 2022). Author contributions: S.L. contributed to the animal experiments and analysis. M.Z. and J.X. contributed to the peptide synthesis and porous gel fabrication. Y.D. contributed to the cell culture and qPCR assay. X.C. contributed to the polymer synthesis and NMR characterization. K.W. contributed to the macromer synthesis and proofreading of the manuscript. R.L. contributed to the rest of the experiments and the manuscript. G.L. led the in vivo study of the project. L.B. led the project as the supervisor. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.
Stem Cell Banking Market was valued at $1986 million in 2016 – Markets Gazette
By daniellenierenberg
A fresh report titled Stem Cell Banking Market has been presented by KD market insights. It evaluates the key market trends, advantages, and factors that are pushing the overall growth of the market. The report also analyzes the different segments along with major geographies that have more demand for Stem Cell Banking Market. The competition analysis is also a major part of the report.
The global stem cell banking market was valued at $1,986 million in 2016, and is estimated to reach $6,956 million by 2023, registering a CAGR of 19.5% from 2017 to 2023. Stem cell banking is a process where the stem cell care isolated from different sources such as umbilical cord and bone marrow that is stored and preserved for future use. These cells can be cryo-frozen and stored for decades. Private and public banks are different types of banks available to store stem cells.
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Increase in R&D activities in regards with applications of stem cells and increase in prevalence of fatal chronic diseases majorly drive the growth of the global stem cell banking market. Moreover, the large number of births occurring globally and growth in GDP & disposable income help increase the number of stem cell units stored, which would help fuel the market growth. However, legal and ethical issues related to stem cell collections and high processing & storage cost are projected to hamper the market growth. The initiative taken by organizations and companies to spread awareness in regards with the benefits of stem cells and untapped market in the developing regions help to open new avenues for the growth of stem cell banking market in the near future.
The global stem cell banking market is segmented based on cell type, bank type, service type, utilization, and region. Based on cell type, the market is classified into umbilical cord stem cells, adult stem cells, and embryonic stem cells. Depending on bank type, it is bifurcated into public and private. By service type, it is categorized into collection & transportation, processing, analysis, and storage. By utilization, it is classified into used and unused. Based on region, it is analyzed across North America, Europe, Asia-Pacific, and LAMEA.
KEY MARKET BENEFITS
This report offers a detailed quantitative analysis of the current market trends from 2016 to 2023 to identify the prevailing opportunities.
The market estimations provided in this report are based on comprehensive analysis of the key developments in the industry.
In-depth analysis based on geography facilitates in analyzing the regional market to assist in strategic business planning.
The development strategies adopted by key manufacturers are enlisted in the report to understand the competitive scenario of the market.
KEY MARKET SEGMENTS
By Cell Type
Umbilical Cord Stem Cell
Cord Blood
Cord Tissue
Placenta
Adult Stem Cell
Embryonic Stem Cell
By Bank Type
Public
Private
By Service Type
Collection & Transportation
Processing
Analysis
Storage
By Utilization
Used
Unused
By Region
North America
U.S.
Canada
Mexico
Europe
Germany
UK
France
Spain
Italy
Rest of Europe
Asia-Pacific
Japan
China
Singapore
India
South Korea
Rest of Asia-Pacific
LAMEA
Brazil
Saudi Arabia
South Africa
Rest of LAMEA
KEY PLAYERS PROFILED
Cord Blood Registry
ViaCord
Cryo-Cell
China Cord Blood Corporation
Cryo-Save
New York Cord Blood Program
CordVida
Americord
CryoHoldco
Vita34
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Table of Content
CHAPTER 1: INTRODUCTION
1.1. Report description1.2. Key benefits for stakeholders1.3. Key market segments1.4. Research methodology
1.4.1. Secondary research1.4.2. Primary research1.4.3. Analyst tools and models
CHAPTER 2: EXECUTIVE SUMMARY
2.1. CXO perspective
CHAPTER 3: MARKET OVERVIEW
3.1. Market definition and scope3.2. Key findings
3.2.1. Top investment pockets3.2.2. Top winning strategies
3.3. Porters five forces analysis3.4. Top Player Positioning3.5. Market dynamics
3.5.1. Drivers
3.5.1.1. Large number of newborns3.5.1.2. Increase in R&D activities for application of stem cells3.5.1.3. Increase in prevalence of fatal chronic diseases3.5.1.4. Growth in GDP and disposable income
3.5.2. Restraints
3.5.2.1. Legal and ethical issues during collection of stem cells3.5.2.2. High processing and storage cost3.5.2.3. Lack of acceptance and awareness
3.5.3. Opportunities
3.5.3.1. Initiatives to spread awareness3.5.3.2. Untapped market in developing regions
CHAPTER 4: STEM CELL BANKING MARKET, BY CELL TYPE
4.1. Overview
4.1.1. Market size and forecast
4.2. Umbilical Cord Stem Cells
4.2.1. Key market trends and growth opportunities4.2.2. Market size and forecast4.2.3. Market analysis, by country4.2.4. Cord Blood
4.2.4.1. Market size and forecast
4.2.5. Cord Tissue
4.2.5.1. Market size and forecast
4.2.6. Placenta
4.2.6.1. Market size and forecast
4.3. Adult stem cells
4.3.1. Key market trends and growth opportunities4.3.2. Market size and forecast4.3.3. Market analysis, by country
4.4. Embryonic stem cells
4.4.1. Key market trends and opportunities4.4.2. Market size and forecast4.4.3. Market analysis, by country
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KD Market Insights offers a comprehensive database of syndicated research studies, customized reports, and consulting services. These reports are created to help in making smart, instant and crucial decisions based on extensive and in-depth quantitative information, supported by extensive analysis and industry insights.
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Stem Cell Banking Market was valued at $1986 million in 2016 - Markets Gazette
How Young India is fuelling the future of stem cell therapy and signing up to save lives – YourStory
By daniellenierenberg
Eighteen-year-old Aisha Choudhary was just like any other adolescent eyes filled with dreams and a heart brimming with energy. The only difference was she was battling a rare genetic disease, Severe Combined Immune Deficiency (SCID). Diagnosed when she was six months old and undergoing medical treatment for years, she was iron-willed in playing the cards she was dealt.
Since one of the most effective cures for SCID is a stem cell transplant (grafting of the parent cells from which all blood cells develop), Aishas parents, Niren and Aditi, decided to opt for that treatment mode. But their cells were not a complete match with their daughters, and they had to look at external donors. However, due to a low number of voluntary, registered stem cell donors, Aisha could not get a compatible donor whose genetic markers were a close enough match to hers. With no other alternative treatment available, Aisha had a bone marrow transplant. But, it came with a side-effect that cost her life Pulmonary Fibrosis, a disease known to damage the lung tissues.
Aishas Choudhary's role has been played by Zaira Wasim in The Sky is Pink.
Aishas journey has been captured in The Sky is Pink, a recent Bollywood movie starring Priyanka Chopra, Farhan Akhtar, Zaira Wasim, and Rohit Saraf.
The 18-year-olds life story is mirrored in the experiences of many who await stem cell donation as treatment for blood-related illnesses likeleukemia, lymphoma, and sickle cell anemia every year. With very few individuals signing up as donors and the probability of finding a match being a dismal 0.0008 percent in India (against a lean 16 percent abroad), fatalities are mounting year on year.
However, in recent times, there has been one small break in the clouds a number of youngsters, non-governmental organisations, and medical professionals have come forward and are working to spread awareness about stem cell donation and motivate a larger number of people to register as donors.
The stem cells in a human body mainly comprise red blood cells, platelets, and white blood cells. These are found in the umbilical cord of newborns and in the peripheral or circulating blood and bone marrow.
A stem cell donation is as simple and painless as a blood donation.
Certain diseases like blood cancer and leukemia tend to destroy the bone marrow or affect its functioning.For these, treatments like chemotherapy and radiotherapy are tried initially. However, in some cases, they do not prove effective for a cure. The only recourse then is replacing the patients stem cells with those of a healthy person.
One of the main criteria for a successful transplant is a good match between the stem cells of the donor and those of the patient. Therefore, a donor registry will administer a cheek swab test (tissue samples extracted from the cheek) on all potential donors to match cell characteristics. This procedure of pairing generic markers is called Human Leukocyte Antigen (HLA) in medical terms.
A cheek swab test in progress.
Each potential donors tissue is entered in the registry and given an identification number after the test is done. If the registry finds a match at any point in time, the donor is contacted to initiate the transplant.
There are many organisations today that are leading the charge in saving the lives of people suffering from serious blood disorders like cancer, thalassemia, and anaemia.
For instance, Datri, an Ahmedabad-based NGO, is working to create a wide and diverse database of potential stem cell donors by organising donation drives. Founded in 2009 by two doctors and an engineer, the organisation focuses on conducting awareness campaigns and helping individuals sign up on its registry as a committed and voluntary benefactor.
The team of the NGO Datri.
The idea for Datri was initially born in the minds of doctors Nezih Cereb and Soo Young Yang, who run a laboratory, Histogenetics, for determining tissue matches between patients and donors. Since pairing tissue types is imperative for any stem cell transplant, and confronting a severe shortage of donors, the doctor duo would run from pillar to post to meet hospitals requirements. Working with a number of the hospitals in India, they realised just how acute the shortfall was in people willing to donate stem cells. They recognised the immediate need to create a donor registry here.
Soon after, Raghu Rajagopal, an engineer from BITS Pilani and Director of ready-to-eat venture Millets and More, connected with them and they decided to start Datri.
Today, the functioning of the registry, its maintenance, and even the substantial costs involved in conducting the HLA matching are taken care of by the lab. In the last 10 years, Datri has gotten over four lakh people to register as donors and has saved around 600 lives through successful transplantation.
Every day, about 40 people are diagnosed with blood disorders in India. Though these can be cured through a stem cell transplant from a genetically matched donor, there is only a 25 percent chance of finding a match from within the family. Others have no option but to rely on unrelated donors. But the chances of getting a match is anywhere between one in 10,000 and one in two million. There is an urgent need to rope in as many potential donors as possible, which is precisely what Datri is trying to do, Raghu explains.
Another organisation that is dedicated to fighting blood disorders with stem cell treatment is DKMS-BMST. It was formed through a joint venture between two renowned NGOs DKMS, which is one of the largest international blood stem cell donor centres globally, and the Bangalore Medical Services Trust (BMST).
The team of DKMS-BMST.
DKMS was founded in Germany in 1991 by businessman Dr Peter Harf, after he lost his wife to leukemia. BMST was born in 1984 from the vision of Dr Latha Jagannathan, a medical director and managing trustee. Since both organisations had a common goal to find a matching donor for every patient with a blood disorder, they decided to come together to achieve it.
A group of youngsters registering to be stem cell donors.
So far, more than 37,000 people in India have registered as potential donors after attending DKMS-BMSTs donor drives.
In highly populous countries like India, thousands of people are in need of stem cell transplants every year to survive. Though donating stem cells is a painless and non-invasive process, it remains a lesser-known medical concept in India, with only 3.6 lakh people willing to play a part in it. Besides, the chances of stem cells of people of the same ethnicity matching are higher than those of individuals from different ethnic backgrounds. But, it is due to sheer lack of awareness that India lags severely in stem cell donations, say experts.
Students taking a cheek swab test at one of the colleges in Bengaluru.
Dr Govind Eriat, a reputed hematologist and bone marrow transplant specialist, says,
With a major hurdle to stem cell donation in India proving to be the myths surrounding the subject, the youth are coming forward to deconstruct common misconceptions.
For instance, 21-year-old Tejaswini Patel, a student of Information Science at New Horizon College of Engineering, Bengaluru, has been busting the false ideas on stem cell donation, starting among her family and friends. She says,
She adds, with a notable sense of pride, In the last two years alone, around 400 students from my college have registered themselves as donors.
(Edited by Athirupa Geetha Manichandar)
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How Young India is fuelling the future of stem cell therapy and signing up to save lives - YourStory
ARMI summit: With synthetic meat within grasp, why not synthetic liver? – The Union Leader
By daniellenierenberg
MANCHESTER Now that the world has the Impossible Whopper, will the impossible liver be far behind?
Such possibilities are being broached this week as inventor Dean Kamen, founder of the Advanced Regenerative Manufacturing Institute, hosts the fourth semi-annual summit since launching ARMI in July 2017.
The three-day conference started Tuesday with a members-only day for BioFab USA and ARMI. It included a dinner at Kamens Bedford home.
Two public days of speeches and workshops are scheduled through Thursday. A total of 150 have signed up for the event.
Guests listen to a speaker at the Meeting in the Millyard at ARMI in Manchester on Wednesday, Oct. 16, 2019.
The keynote speaker on Wednesday was Jason Kelly, co-founder and chief-executive of Ginkgo Bioworks, a synthetic biology company that programs cells for customers in the chemical, pharmaceutical, food and energy industries.
We program cells because they run on digital code in the form of DNA, Kelly told a crowd of scientists, entrepreneurs and regulators.
Much of ARMIs work has focused on the use of stem cells to generate replacements for human tissue, bones and organs. For example, one of ARMIs biggest accomplishments to date has been the Tissue Foundry; its first production was bone-ligament tissue grown together from bone-marrow stem cells.
But Kamen, who prides himself on introducing new technologies to a field, had Kelly speak about a different kind of cells synthetic cells.
Ginkgo Bioworks has partnered with Bayer to develop self-fertilizing crops, with Roche to develop antibiotics, and with Motif to produce animal-free protein ingredients. Kelly said synthetic cell production played a role in the Impossible Whopper, the plant-based patty that Burger King claims tastes like beef.
(According to the website of Impossible Food, the company that makes the patty, the company extracts DNA from soy plants and inserts it into genetically engineered yeast, which ferments to produce heme, the molecule that gives meat its taste.)
Ginkgo has made CNBCs Disruptor 50 List in the last three years and recently raised more than $430 million in venture capital. In doing so, Ginkgo has achieved what Kamen wants for ARMI to move from theoretical design and laboratory work to mass production.
Theyve learned how to scale it, Kamen said in his introduction. Kamen said he expects ARMI-linked production to start relatively quickly.
(Finding) talent is not the problem. Capital is the problem, Kelly said about tech startups. Many venture capitalists arent experts in the science-heavy world of what he calls tough tech. So they are wary about investing in something they cant grasp.
He advised startups to seek government grants Ginkgo would not have succeeded without them hustle the non-specialist investor and find third-party validation from agencies such as the FDA or the Standards Coordinating Body, a voluntary organization that sets standards for the regenerative medicine industry.
Kelly said the time is now for tough tech. He noted the work of SpaceX and Tesla, and he said Silicon Valley is embracing biotech.
People have run out of things to invent that end up as a square on your phone, he said.
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ARMI summit: With synthetic meat within grasp, why not synthetic liver? - The Union Leader
The Week That Wasn’t: Viagra BMTs, Pregnancy Stress, Breast Cancer Vaccine – Medscape
By daniellenierenberg
Stories of using the little blue pill for bone marrow transplants, how pregnancy stress is related to the baby's sex, and a vaccine for breast cancer proliferated on the Internet this week. Here's why you didn't read about them on Medscape.
Researchers at the University of California, Santa Cruz, seem to think Viagra has more to offer in medicine. In a recent study of mice, they tested whether the vasodilator couldspeed up the migration of hematopoietic stem cells and progenitor stem cells from the bone to the blood, where the cells could be harvested noninvasively.
The standard protocol for preparing bone marrow donors for the harvesting procedure, a 5-day regimen of granulocyte-colony stimulating factor (G-CSF),is "complex, costly, unsuccessful in a significant proportion of donors," the study authors write, and typically results in fatigue, nausea, and bone pain. Using a two-drug strategy, oral Viagra and a single injection of the CXCR4 antagonist AMD3100 (plerixafor), elicited the same mobilization of stem cells in 2 hours.
We didn't cover the study because it's still too early to say whether this strategy might be effective in people. After this mouse study, the next step is testing the approach in larger animals before human clinical trials.
A study of 187 healthy pregnant women age 18 to 45 years suggests that preterm mental and physical stress may be related to the baby's sex and increase the risk for preterm birth. In the study, 16% of women were physically stressed, as measured by higher blood pressure and calorie intake; and 17% were mentally stressed with high levels of depressionand anxiety; 66% of the women were in the healthy (nonstressed) group.
Women who were stressed during pregnancy were more likely to give birth to a girl. Typically, 105 males are born for every 100 females, but the study authors found that the male-to-female ratio decreased to 2:3 in psychologically stressed patients and 4:9 in physically stressed patients. Physically stressed mothers also gave birth an average of 1.5 weeks earlier than mothers in the healthy group, with 22% giving birth preterm compared with 5% in the healthy group.
The study authors say the findings demonstrate the importance of maternal mental health. Medscape has covered the consequences of maternal stress extensively, including preterm birth, neurobehavioral risks, and potential links to hyperactivity during the offspring's teen years. However, the sample size in this study was small: the mentally and physically stressed groups combined only included about 60 women. That's not sufficient to inform clinical practice in counseling women who want to get pregnant about how stress may affect the sex of their baby, so we didn't cover it.
News spread this week that Floridian Lee Mercker became the first woman to "beat" breast cancer with the help of a new vaccine. The vaccine, which stimulates the immune system to fight off early-stage breast cancer, was developed and administered by researchers at the Mayo Clinic in Jacksonville, Florida. The vaccine is currently in an early trial.
Reports of Mercker's success raise hopes, but she's reportedly the first participant in the trial. The news report also says she underwent a double mastectomy after her diagnosis in March, so it's unclear what evidence of the vaccine's efficacy the researchers measured. Before this experimental vaccine is relevant to Medscape readers, we need to see additional detailed data from more patients in the clinical trial published in a peer-reviewed journal.
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The Week That Wasn't: Viagra BMTs, Pregnancy Stress, Breast Cancer Vaccine - Medscape
Bone marrow recipient comes face-to-face with CT donor for the first time – WTNH.com
By daniellenierenberg
BRIDGEPORT, Conn. (WTNH) The Gift of Life Marrow Registry organized the meeting Thursday between a bone marrow donor from Connecticut and the recipient whose life was saved by the donation.
Jennie Bunce, 25, of Redding donated her marrow. According to a representative for Gift of Life, Bunce was studying physical therapy and joined Gift of Life through a sorority event at North Carolinas High Point University in 2016.
I never win or get picked for anything, but it just felt like the right thing to do, Bunce told Gift of Life. Im just incredibly happy and grateful to be part of something so special. Its similar to holding the door open for someone or helping a friend in a time of need.
Across the country in Mesa, Arizona, father-of-6, Mark Roser, 33, was battling Acute Lymphoblastic Leukemia. He found out about the diagnosis after he broke a hip in 2018 and had continued weakness. Roser was told he needed a bone marrow transplant to survive.
The hardest part was knowing, no matter how hard I worked, that what I did would not be a deciding factor in my ability to receive this gift, said Roser.
The match was made by Gift of Life in about six months, and the transplant took place in Phoenix.
She is a hero to all the people in my life, said Roser.
She gave me life, she gave my children a future with their dad, she gave my wife a chance to hold her husband, to have someone hold her back. She allowed me to go to work, to play, to see things from a different perspective. I am grateful for every moment I have, and its because of her.
According to Gift a Life, medical privacy laws dictate that recipients and donors must remain anonymous and wait at least a year before meeting.
The two came face-to-face for the first time Thursday in Bridgeport at the Boca Oyster Bar.
Since its start in 1991, the Gift of Life Registry 349,000 individuals who have donated blood stem cells or bone marrow to save a life. The program has facilitated 16,800 matches and over 3,500 transplants.
To learn more about the organization and/or how to donate: https://www.giftoflife.org/.
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Bone marrow recipient comes face-to-face with CT donor for the first time - WTNH.com