Bone Marrow Protein May Be Target for Improving Stem Cell Transplants – Penn: Office of University Communications
By NEVAGiles23
Bone marrow contains hematopoetic stem cells, the precursors to every blood cell type. These cells spring into action following bone marrow transplants, bone marrow injury and during systemic infection, creating new blood cells, including immune cells, in a process known as hematopoiesis.
A new study led by University of Pennsylvania and Technical University of Dresden scientists has identified an important regulator of this process, a protein called Del-1. Targeting it, the researchers noted, could be an effective way to improve stem cell transplants for both donors and recipients. There may also be ways to modulate levels of Del-1 in patients with certain blood cancers to enhance immune cell production. The findings are reported this week in The Journal of Clinical Investigation.
Because the hematopoetic stem cell niche is so important for the creation of bone marrow and blood cells and because Del-1 is a soluble protein and is easily manipulated, one can see that it could be a target in many potential applications, said George Hajishengallis, the Thomas W. Evans Centennial Professor in the Department of Microbiology in Penns School of Dental Medicine and a senior author on the work.
I think that Del-1 represents a major regulator of the hematopoetic stem cell niche, said Triantafyllos Chavakis, co-senior author on the study and a professor at the Technical University of Dresden. It will be worthwhile to study its expression in the context of hematopoetic malignancy.
For Hajishengallis, the route to studying Del-1 in the bone marrow began in his field of dental medicine. Working with Chavakis, he had identified Del-1 as a potential drug target for gum disease after finding that it prevents inflammatory cells from moving into the gums.
Both scientists and their labs had discovered that Del-1 was also expressed in the bone marrow and began following up to see what its function was there.
In the beginning, I thought it would have a simple function, like regulating the exit of mature leukocytes [white blood cells] from the marrow into the periphery, Hajishengallis said, something analogous to what it was doing in the gingiva. But it turned out it had a much more important and global role than what I had imagined.
The researchers investigations revealed that Del-1 was expressed by at least three cell types in the bone marrow that support hematopoetic stem cells: endothelial cells, CAR cells and osteoblasts. Using mice deficient in Del-1, they found that the protein promotes proliferation and differentiation of hematopoetic stem cells, sending more of these progenitor cells down a path toward becoming myeloid cells, such as macrophages and neutrophils, rather than lymphocytes, such as T cells and B cells.
In bone marrow transplant experiments, the team discovered that the presence of Del-1 in recipient bone marrow is required for the transplanted stem cells to engraft in the recipient and to facilitate the process of myelopoesis, the production of myeloid cells.
When the researchers mimicked a systemic infection in mice, animals deficient in Del-1 were slower to begin making myeloid cells again compared to those with normal Del-1 levels.
We saw roles for Del-1 in both steady state and emergency conditions, Hajishengallis said.
Hajishengallis, Chavakis and their colleagues identified the protein on hematopoetic stem cells with which Del-1 interacts, the 3 integrin, perhaps pointing to a target for therapeutic interventions down the line.
The scientists see potential applications in bone marrow and stem cell transplants, for both donors and recipients. In donors, blocking the interaction between Del-1 and hematopoetic stem cells could enhance the mobilization of those progenitors into the bloodstream. This could be helpful for increasing donor cell numbers for transplantation. Transplant recipients, on the other hand, may need enhanced Del-1 interaction to ensure the transplanted cells engraft and begin making new blood cells more rapidly.
In addition, people undergoing chemotherapy who develop febrile neutropenia, associated with low levels of white blood cells, might benefit from the role of Del-1 in supporting the production of immune-related blood cells such as neutrophils.
Its easy to think of practical applications for these findings, said Hajishengallis. Now we need to find out whether it works in practice, so our studies continue.
Ioannis Mitroulis, Lan-Sun Chen and Rashim Pal Singh of TU-Dresden were co-lead authors on the study, and Ben Wielockx of TU-Dresden was a co-senior author along with Hajishengallis and Chavakis. They were joined by coauthors Tetsuhiro Kajikawa, Kavita Hosur, Tomoki Maekawa and Baomei Wang of Penn Dental Medicine; Ioannis Kourtzelis, Matina Economopoulou, Maria Troullinaki, Athanasios Ziogas, Klara Ruppova, Pallavi Subramanian, Panayotis Verginis, Malte Wobus, Martin Bornhuser and Tatyana Grinenko of TU-Dresden; Torsten Tonn of the German Red Cross Blood Donation Service in Dresden; and Marianna Di Scala and Andrs Hidalgo of the Spanish National Center for Cardiovascular Research.
The study was supported by the Deutsche Forschungsgemeinschaft, European Commission, European Research Council and National Institutes of Health (grants AI068730, DE024153, DE024716, DE0152 54 and DE026152).
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Bone Marrow Protein May Be Target for Improving Stem Cell Transplants - Penn: Office of University Communications
Creative Medical Technology Holdings Achieves 100% Patient Enrollment in CaverstemTM Clinical Trial for Stem Cell … – Markets Insider
By daniellenierenberg
PHOENIX, Aug. 28, 2017 /PRNewswire/ -- Creative Medical Technology Holdings Inc. (OTCQB ticker symbol CELZ) announced today completion of enrollment in the Company's clinical trial assessing safety and efficacy of its CaverstemTM procedure to treat erectile dysfunction in patients who do not respond to currently available treatments.Approximately 30% of the 30,000,000 patients suffering from erectile dysfunction do not respond to drugs like Viagra, Cialis and Levitra, in part due to an underlying degeneration of the biological machinery needed to achieve erections.
"The CaverstemTM procedure, which uses the patient's own bone marrow derived stem cells to induce arterial and venous regeneration, is an outpatient procedure able to be conducted by Urologists in their medical facilities. We are using a patient's own cells and we do not manipulate the stem cells through the use of chemicals, growth factors or expansion and have experienced no procedure-related safety issues," said Dr. Thomas Ichim Co-Founder and Chief Scientific Officer of Creative Medical Technology Holdings, Inc.
The clinical trial covering patients ages 18 to 80 received Institutional Review Board (IRB) approval in December 2016. The trial is sponsored by us based on our patented technology and is conducted by Dr. Jacob Rajfer, Principal Investigator and Los Angeles Biomedical Institute at Harbor UCLA Hospital in Torrance, CA.
"I am pleased with the expedience and efficiency at which enrollment was reached. As someone who regularly sees patients suffering from treatment non-responsive erectile dysfunction, I am excited to see the development of a novel approach to treating this condition using the patient's own natural regenerative processes," said Dr. Alexander Gershman, member of the Company's Scientific Advisory Board and Director of Institute of Advanced Urology at the Cedars-Sinai Medical Tower; Director of Urologic Laparoscopy in the Division of Urology, Harbor-UCLA Medical Center."
"We are very fortunate to work with the expert team at Los Angeles Biomedical Institute - UCLA/Harbor Hospital who have done an outstanding job with subject recruitment, screening, treatment and follow-up.We firmly believe that we are on schedule for commercialization of the Caverstem TM procedure through publication and presentation of trial results, marketing, licensing, training and sales in 2018," said Timothy Warbington, President and CEO of Creative Medical Technology Holdings Inc.
About Creative Medical Technology Holdings
Creative Medical Technology Holdings, Inc. is a clinical stage biotechnology company currently trading on the OTCQB under the ticker symbol CELZ. For further information about the company go to http://www.creativemedicaltechnology.com. For more information on our CaverstemTM procedure please go to http://www.caverstem.com.
Forward-Looking Statements
OTC Markets has not reviewed and does not accept responsibility for the adequacy or accuracy of this release. This news release may contain forward-looking statements including but not limited to comments regarding the timing and content of upcoming clinical trials and laboratory results, marketing efforts, funding, etc. Forward-looking statements address future events and conditions and, therefore, involve inherent risks and uncertainties. Actual results may differ materially from those currently anticipated in such statements. See the periodic and other reports filed by Creative Medical Technology Holdings, Inc. with the Securities and Exchange Commission and available on the Commission's website at http://www.sec.gov.
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Creative Medical Technology Holdings Achieves 100% Patient Enrollment in CaverstemTM Clinical Trial for Stem Cell ... - Markets Insider
Struggling with a chronic or life-threatening illness? Your blood can help research cures – Sacramento Bee
By Sykes24Tracey
For anyone diagnosed with cancer, Alzheimers or AIDS, perhaps the best hope for finding cures lies in their own bodies more specifically, in the cells traveling through their blood.
Scientists at major universities and pharmaceutical companies need more of those cells to do their cutting-edge medical research, and Folsoms StemExpress is leading the way nationwide. Company CEO Cate Dyer is trying to get out the word to potential donors that their blood is essential to this work.
StemExpress collects blood, bone marrow, plasma or cord blood at its centers and compensates donors for their time and discomfort. Then it processes their samples into a range of products, including many of the cells on your bodys healing team: white blood cells, stem cells, T cells and others that answer the call when the body confronts a disease or disability.
We really want to get out to people in Sacramento and the region that we need diseased donors at our sites, and thats everyone people who have an early-diagnosed cancer, people in treatment, theyre having radiation post-treatment and remission, from everything like AML, leukemia, lymphoma, all of the major cancer space, said Cate Dyer, the companys founder and CEO. But also, we have AIDS projects going on right now where we need AIDS-positive samples.
Its not just cancer or AIDS, though. Some researchers also use cells from the samples to study chronic diseases such as diabetes and high blood pressure or to study illnesses that have no cures such as Alzheimers or Parkinsons.
Researchers can take many paths when studying cells from different people, at different stages of a disease, said Dr. Michael Chez, a pediatric neurologist with Sutter in the Sacramento region. For example, researchers could develop screenings for early detection of a disease or genetic defect, or duplicate defective tissues to see how to repair what went wrong. Their findings might help to develop drugs or chemicals that will help to reverse or change the course of a disease. Already, scientists have begun harvesting stem cells, turning them into specific tissues and using them for replacement or repair.
To help potential donors understand the impact they can have on research, Dyer highlighted the work that StemExpress started doing seven years ago with San Diego-based Sequenom, a life-sciences company that was attempting to develop a less-invasive way to check for genetic defects in fetuses. At the time, doctors were using a needle, pushing through the wall of the abdomen and into the uterus to collect and test elements of the amniotic fluid to assess genetic abnormalities.
It was a procedure that frightened women not only because of concerns about their unborn babies but also because they feared that they might be one of the small percentage of women who suffered a major complication as a result of the amniocentesis.
Sequenom envisioned a test that, by contrast, would simply examine blood drawn from the expectant mother. To develop the test, Sequenoms researchers would have to isolate and study DNA strands for both expectant moms and their fetuses. By studying DNA from thousands of donors, the life sciences company was able to identify DNA mutations, deletions and alterations and develop a way to check for them in the blood rather than in amniotic fluid.
At the time, when I met (Sequenoms senior director of clinical operations) they were sourcing about 25 (blood) samples a week, just to give you a ballpark, Dyer said, and I asked him, Well, how long is it going to take you to meet all the (Food and Drug Administration) requirements needed, sourcing 25 samples a week? And, he was like, Five to six years to get all our projects together.
Dyer made it her priority to significantly speed up that development timeline by delivering 300 samples a week, a feat she said the company accomplished within 90 days. Along the way, Stem Express became the largest global supplier of maternal blood for research purposes.
If it takes six years for them to source all the samples and another year and a half to get that through the FDA, youre looking at an eight-year turnaround just to get that ... to a patient, Dyer said. If we can shorten that, which we did, to almost a year and a half and get that then to the FDA and back out to patients, weve just massively impacted patient health care.
Chez talks regularly with patients or the parents of patients who are impatient for better treatments or cures, he said, but the availability of donor blood, cells and DNA already has sped up the pace of development of new drugs, screenings or treatments, and that pace should continue to improve as the bank of samples grows.
What also excites Chez is that multiple researchers can benefit from the millions of cells extracted from a blood draw from a single patient. Think of what this means, he said, for orphan diseases those conditions that affect fewer than 200,000 U.S. residents, such as Lou Gehrigs, cystic fibrosis or muscular dystrophy. A physician might run into a patient with one of these conditions once every 10 years, he said, but a few people living with these illnesses now have the power to provide cells to foster research around the world.
Experts then can study how a disease manifests at the cellular level, design methods of treatment and test them on human tissue in the lab, Chez said. There may not be enough patients in any one place to design treatment studies, he said, so human tissues can expand statistical ways to study the safety and efficacy of treatments.
One patient could help a disease study in multiple places versus just being limited to one researcher at one university, Chez said. If you have multiple people doing the work, it just amplifies how quickly things get done and the statistical power of that type of research. This is exponentially changing the algorithm of how research will be done in disease.
Dyer said she is often asked: Could giving blood pose a health risk for people struggling with cancer or other diseases? Her answer: It depends on the patient. StemExpress puts each donor through health assessments to determine how much blood they can give. Some patients may only be able to give one tablespoon; others, as much as six tablespoons.
Patients receive $25-$50 for blood draws, fees that are set by an independent review board. The company has collection centers at 2210 E. Bidwell St. in Folsom, another in Arlington, Mass., and is working to open another center in San Diego.
Researchers are typically specific about the kinds of diseased blood they need and even the stage or progression, Dyer said, so StemExpress is working to expand its donor database to ensure it has a variety of the cells needed.
Want to support biomedical research?
StemExpress is seeking people willing to give blood, white blood cells and bone marrow. The company accepts donations from patients who are healthy or those struggling with chronic or terminal illnesses.
The company compensates donors, based on the time they spend and the invasiveness of the procedure. People who give blood receive $25-50, for instance, while marrow donors receive $250.
A review board, independent of StemExpress, sets the payments. To learn more or to make an appointment, visit http://www.stemexpressdonors.com or call 1-877-900-7836.
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Struggling with a chronic or life-threatening illness? Your blood can help research cures - Sacramento Bee
Eliminating the need for bone marrow donors – The Hippocratic Post (blog)
By raymumme
Researchers are looking for ways eliminate the need for bone marrow donors altogether and instead use different types of cells derived from the patient in need of a transplant, says Dr Vladislav Sandler.
At the moment, people who develop leukaemia, lymphoma and otherblood diseases often need to undergo a hematopoietic stem cell transplantation (HSCT). This is because initial treatment of the disease (front-line therapy) often fails and the disease comes back.
Hematopoietic stem cells (HSC) are vital because they constantly regenerate the blood system giving rise (differentiating) into all types of blood cells such as red blood cells, white blood cells and platelets. Sometimes,patients get cells for the HSCT from close relatives (related allogeneic transplantation), who happen to be a match or by using donor data bases that can match them with strangers (unrelated allogeneic transplantation). The patients own HSC are wiped out with chemotherapy and replaced with donated blood-forming steam cells which create healthy new blood cells free from disease.
The patients own HSC are wiped out with chemotherapy and replaced with the donated blood-forming stem cells which createhealthy new blood cellsfree from disease.
Often, there is not a perfect match between a donor and a patient but physicians try and find the closest one possible. When a match is not perfect, a risk of rejection of the newly transplanted cells significantly grows. There are several teams of researchers trying to find a way to eliminate the need for bone marrow donors altogether and instead use different types of cells derived from the patient in need of a transplant.
This work, to directly reprogram the patients own cells to create hematopoietic stem cells, (from which all cellular blood components are derived) has been going on for some time and has had some success[1][2][3]. However, it is a very long and cumbersome process to produce HSC cells from a patients own cells and it looks like this may never be a practicable solution to the problem. We simply cant seem to be able to get the newly formed HSC cells to replicate into the sufficient number of cells needed to form a viable HSCT.
What I discovered when I was at Cornell University was that there is a small subset of postnatal hemogenic endothelial cells (Hu-PHEC) which survive in the liver and blood vessels of the umbilical cord and placenta into adulthood. It has been known for quite a while that in the fetus, similar cells produce first definitive HSC. It was accepted as a dogma that they either lose their ability to do this after birth or simply disappear. However, as it often happens in science, this was not entirely correct. Hu-PHEC can be isolated from postnatal tissues and made to generate HSCde-novo.
In animal experiments, we took purified and stimulated Hu-PHEC and transplanted them into immunocompromised mice.
What we found was that the transplanted cells did engraft and created a healthy new human blood system in the recipient mice. What seemed to happen was that by putting them back into circulation within the body reactivated their ability to produce HSC cells as they doin utero.
We dont yet understand the mechanism but we are working on this and we need to work out a way to get enough cells for human transplantation.
Development of Hu-PHEC technology would create an opportunity to get rid of bone marrow/HSC donations. We would no longer have to go to a donor or a family member, but simply harvest some of these special post-natal hemogenic endothelial cells from the patients own body.
Another area of our research has been to develop a conditioning product which helps eliminate the patients diseased HSC with minimal collateral damage to the rest of the body. At the moment, patients undergo a rather terrible process of preparation for a HSCT. It involves chemotherapy and radiation and can seriously harm various unrelated healthy cells. In some cases, patients do not survive the conditioning process. We have developed a type of immune therapy which is a bi-specific antibody that redirects patients own immune cells to only attack and kill HSC. It leaves other cells alone, so does not damage reproductive system. This should mean that men and women undergoing conditioning in advance of a bone marrow transplantion would not need to undergo fertility saving treatment (no need to freeze sperm or eggs). This bi-specific antibody, which is filed for a world-wide patent, is much less dangerous and detrimental to health than current treatment options. We have proved its effectiveness in animal trials, but we are now hoping to move on to Phase 1 clinical trials within the next two years.
[1]Sandler, V. M. et al. Reprogramming human endothelial cells to hematopoietic cells requires vascular induction. Nature 511, 312-318, doi:10.1038/nature13547 (2014).Validated in: Lis, R. et.al. Conversion of adult endothelium to immunocompetent hematopoietic stem cells. Nature Published online 17 May 2017, doi:10.1038/nature22326 (2017).
[2]Sandler V.M et al.Reprogramming of Embryonic Human Fibroblasts into Fetal Hematopoietic Progenitors by Fusion with Human Fetal Liver CD34+ Cells. PLoS ONE 6(4) 2011.
[3] Pereira C.F. et al. Induction of a hemogenic program in mouse fibroblasts. Cell Stem Cell. 2013 Aug 1;13(2):205-18.
Vladislav Sandler is the co-founder of HemoGenyx LLC, a US preclinical stage biotechnology company launching innovative new treatments for blood diseases using blood-forming (hematopoietic) stem cell transplantation (HSCT) techniques.
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Eliminating the need for bone marrow donors - The Hippocratic Post (blog)
MS sufferer gets pioneering stem cell treatment – Gloucestershire Live
By raymumme
Multiple sclerosis sufferer Roy Palmer is about to embark on the next phase of his pioneering treatment.
But it comes with risks he is prepared to take in the hope it will cure the debilitating condition.
The 43-year-old father of two from Quedgeley is determined it will work. He was diagnosed with relapsing remitting MS but now has the secondary progressive form of the disease, which means it gets steadily worse.
He said: I fought for a year to get hematopoietic stem cell transplantation and many people told me I didnt fit the criteria but I didnt let that stop me.
Mr Palmer had a week of injections to draw the stem cells from his bone marrow.
He and his wife Helen travelled to Hammersmith Hospital in London where he was given a day of chemotherapy.
Mr Palmer lost his hair as a result and was left feeling sick and tired.
The stem cells have been frozen and will be reintroduced to his body after another aggressive course of chemotherapy.
It will be fed directly into a main artery in his chest before Mr Palmer spends the next four weeks in isolation.
He will start the treatment on September 18 his 24th wedding anniversary.
Mr Palmer said: Im not someone to sit around and feel sorry for myself.
If the treatment works then, oh my God, I couldnt begin to describe what it would mean to me.
He added: To be able to walk out of my front door would mean the world.
I know Im lucky to be able to get the treatment. Im worried, my immune system will be obliterated, but I have to give this everything. Im a fighter and determined to make this work.
Mr Palmers family back his decision to undergo HSCT treatment, although they worry about the effect it will have.
His 45-year-old wife said: When they give the chemotherapy it brings the body back down to zero.
It will stop any immune system and take some time for the body to start getting back to normal.
When Roys levels are up they will start to reintroduce the stem cells.
The MS Society website says HSCT aims to reset the immune system to stop it attacking the central nervous system.
It uses chemotherapy to remove the harmful immune cells and then rebuilds the immune system using haematopoietic stem cells found in bone marrow.
They can produce all the different cells in the blood.
Mrs Palmer said: Im happy for Roy to take that risk and to support him but it is a lethal dose of chemo.
The treatment can be done abroad and costs around 60,000. In the past we were considering that option but there is no aftercare.
The couples daughter Abi, 12, said: I feel a little scared for dad but okay. I cant remember him walking.
And 20-year-old son Jack said: Dad has been in a chair for about 10 years and to see him walk again would mean everything.
Just standing next to each other would mean the world.
Once the stem cells are back in Mr Palmers body the hope is he will make a full recovery and be free of MS,
He said: It will be great to not have to ask people to do things for me.
I do what I can but I dont like to hang around waiting.
I want people to know there is treatment and it can be a fight but Ive got to do this now.
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MS sufferer gets pioneering stem cell treatment - Gloucestershire Live
What is stem cell donation: How does peripheral blood stem cell collection work? – India.com
By JoanneRUSSELL25
It will take you just a few hours to donate stems cells but it will save someones life as it is usually the last or the only resort for those suffering from blood cancer. Stem cells are undifferentiated biological cells that can grow into specialized cells. There are two types of stems cells, which are embryonic stem cells and adult stem cells. Embryonic stem cells are extracted from theblastocyst, which is a structure that contains cell mass that develops into an embryo. Adult stem cells are the undifferentiated cells that replenish the dying cells or repair the damaged cells. These adult stems cells are donated during the stem cell donation. Stems cells are transferred to the patient, where it differentiates into healthy specialized cells. (ALSO READMajor blood types and who can donate blood to whom).
Stem cell donation is voluntarily donating the stem cells produced by your body. It can be donated in two ways. The first method is called Peripheral blood stem cell (PBSC) donation while the other method is bone marrow donation. Bone marrow donation requires hospitalization. Bone marrow is collected from your pelvis by doctors under general anesthesia using a syringe. You may experience pain and bruise but you will recover within a week.
Peripheral blood stem cell donation is used by 90 percent of the people to donate stem cells. It is an easy and quick process to collect the blood-forming cells found in the circulating blood. This non-surgical process of collecting the stem cells is called apheresis.
You need to register to donate stem cell. Your cell sample from cheek is analyzed for HLA typing and when there is a requirement for stem cell with your HLA type, you will get a notification. A complete health check-up is carried out to ascertain that you are fit to donate the stems cells. Once the check up is done, you will be given an injection called GCSF (Granulocyte Colony Stimulating Factor)to increase the stem cell present in your blood. This injection will be administered for five days and on the fifth day, the stem cells are collected. A tiny tube will be inserted in your arm and this tube is connected to a machine that will collect the stem cells. Your blood will pass through the machine. This procedure usually takes about five hours. You may experience flu like symptoms after donating the stem cells but it will soon subside.
Your cells will be given to those suffering from blood cancer and it could save the life of that person.
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What is stem cell donation: How does peripheral blood stem cell collection work? - India.com
miRNA-221 of exosomes originating from bone marrow mesenchymal stem cells promotes oncogenic activity in gastric … – Dove Medical Press
By Dr. Matthew Watson
Min Ma,1,* Shilin Chen,1,* Zhuo Liu,1 Hailong Xie,2 Hongyu Deng,3 Song Shang,1 Xiaohong Wang,4 Man Xia,5 Chaohui Zuo1
1Department of Gastroduodenal and Pancreatic Surgery, Laboratory of Digestive Oncology, Hunan Cancer Institute, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 2Institute of Cancer Research, South China University, 3Department of Laboratory Medicine, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 4Department of Molecular Medicine, College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, 5Department of Gynecological Oncology, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
*These authors contributed equally to this work
Abstract: Worldwide, gastric cancer (GC) is one of the deadliest malignant tumors of the digestive system. Moreover, microRNAs (miRNAs) of exosomes harbored within cancer cells have been determined to induce inflammatory conditions that accelerate tumor growth and metastasis. Interestingly, the oncogenic role of bone marrow mesenchymal stem cells (BM-MSCs) in the modulation of immunosuppression, tumor invasion, and metastasis was discovered to be partly mediated through the secretion of exosomes. In this article, high expression of miRNA-221 (miR-221) in exosomes of the peripheral blood was determined to be positively correlated with the poor clinical prognosis of GC, especially with respect to tumor, node, and metastases stage. Therefore, the expression of miR-221 in exosomes of the peripheral blood may be an important detection index for GC. Proliferation, migration, invasion, and adhesion to the matrix of GC BGC-823 and SGC-7901 cells were significantly enhanced by exosomes that originated from BM-MSCs that were transfected with miR-221 mimics. In conclusion, extracted exosomes from BM-MSCs transfected with miR-221 oligonucleotides can act as high-efficiency nanocarriers, which can provide sufficient miR-221 oligonucleotides to influence the tumor microenvironment and tumor aggressiveness effectively. Notably, the use of a miR-221 inhibitor with an excellent restraining effect in exosomes provides therapeutic potential for GC in future clinical medicine.
Keywords: exosomes, miR-221, BM-MSCs, gastric cancer, prognosis, oncogenic activity
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.
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miRNA-221 of exosomes originating from bone marrow mesenchymal stem cells promotes oncogenic activity in gastric ... - Dove Medical Press
Bacterial infection stresses hematopoietic stem cells – Medical Xpress – Medical Xpress
By Sykes24Tracey
Bacterial infection activates hematopoietic stem cells in the bone marrow and significantly reduces the ability to produce blood through induced proliferation. Credit: Professor Hitoshi Takizawa
It has been thought that only immune cells would act as the line of defense during bacterial infection. However, recent research has revealed that hematopoietic stem cells, cells that create all other blood cells throughout an individual's lifetime, are also able to respond to the infection. A collaboration between researchers from Japan and Switzerland found that bacterial infection activates hematopoietic stem cells in the bone marrow and significantly reduces their ability to produce blood by forcibly inducing proliferation. These findings indicate that bacterial infections might trigger dysregulation of blood formation, such as that found in anemia or leukemia. This information is important to consider in the development of prevention methods for blood diseases.
Background: Bacterial Infection and the Associated Immune Reaction
When a person becomes infected with a virus or bacteria, immune cells in the blood or lymph react to the infection. Some of these immune cells use "sensors" on their surfaces, called Toll-like receptors (TLR), to distinguish invading pathogens from molecules that are expressed by the host. By doing so, they can attack and ultimately destroy pathogens thereby protecting the body without attacking host cells.
Bone marrow contains hematopoietic stem cells which create blood cells, such as lymphocytes and erythrocytes, throughout life. When infection occurs, a large number of immune cells are activated and consumed. It therefore becomes necessary to replenish these immune cells by increasing blood production in bone marrow. Recent studies have revealed that immune cells are not the only cells that detect the danger signals associated with infection. Hematopoietic stem cells also identify these signals and use them to adjust blood production. However, little was known about how hematopoietic stem cells respond to bacterial infection or how it affected their function.
Proof: Hematopoietic Stem Cell Response to Bacterial Infection
Researchers from Kumamoto University and the University of Zurich analyzed the role of TLRs in hematopoietic stem cells upon bacterial infection, given that both immune cells and hematopoietic stem cells have TLRs. Lipopolysaccharide (LPS), one of the key molecules found in the outer membrane of gram negative bacteria and known to cause sepsis, was given to laboratory animals to generate a bacterial infection model. Furthermore, researchers analyzed the detailed role of TLRs in hematopoietic stem cell regulation by combining genetically modified animals that do not have TLR and related molecules, or agents that inhibit these molecules.
The results showed that LPSs spread throughout the body with some eventually reaching the bone marrow. This stimulated the TLR of the hematopoietic stem cells and induced them to proliferate. They also discovered that while the stimulus promoted proliferation, it also induced stress on the stem cells at the same time. In other words, although hematopoietic stem cells proliferate temporarily upon TLR stimulation, their ability to successfully self-replicate decreases, resulting in diminished blood production. Similar results were obtained after infection with E. coli bacteria.
Future Work
This study reveals that hematopoietic stem cells, while not in charge of immune reactions, are able to respond to bacterial infections resulting in a reduced ability to produce blood. This suggests that cell division of hematopoietic stem cells forced by bacterial infection induces stress and may further cause dysregulated hematopoiesis like that which occurs in anemia or leukemia. "Fortunately we were able to confirm that this molecular reaction can be inhibited by drugs," said one of the study leaders, Professor Hitoshi Takizawa of Kumamoto University's IRCMS. "The medication maintains the production of blood and immune cells without weakening the immune reaction against pathogenic bacteria. It might be possible to simultaneously prevent blood diseases and many bacterial infections in the future."
This finding was posted online in Cell Stem Cell on 21 July 2017, and an illustration from the research content was chosen as the cover of the issue.
Explore further: Innate reaction of hematopoietic stem cells to severe infections
More information: Hitoshi Takizawa et al, Pathogen-Induced TLR4-TRIF Innate Immune Signaling in Hematopoietic Stem Cells Promotes Proliferation but Reduces Competitive Fitness, Cell Stem Cell (2017). DOI: 10.1016/j.stem.2017.06.013
Journal reference: Cell Stem Cell
Provided by: Kumamoto University
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Bacterial infection stresses hematopoietic stem cells - Medical Xpress - Medical Xpress
Annual ‘Run for Mandi’ hosting bone marrow registry to combat cancer – Saskatoon StarPhoenix
By LizaAVILA
Erica Honoway is scheduled to speak at the annual "Run for Mandi" charity event in Saskatoon, after her son Lincoln was saved by a bone marrow transplant.Michael Bell / Regina Leader-Post
An annual run honouring a late Canadian hockey player is working with a bone marrow and stem cell registry group in hopes of helping more people in her name.
The Run for Mandi is named for Saskatchewan hockey player Mandi Schwartz, who was diagnosed with acute myeloid leukemia in 2008 while she was part of the Yale Bulldogs hockey team. She died in 2011.
The event kicks off Sunday afternoon at River Landing. The five-kilometre run and the one-kilometre family walk will start at two, and for the first time a bone marrow and stem cell registry group will be set up at the run.
Mandis mother, Carol Schwartz, said shes proud of the work being done by the Mandi Schwartz Foundation in her daughters name.
It just makes these events more meaningful lives are being saved, Schwartz said. Theres probably no greater gift than meeting someone who got a successful match.
The OneMatch Stem Cell and Marrow Network, a part of Canadian Blood Services, will accept registrations at Sundays event. Schwartz said theyve handed out information before, but this is the first time OneMatch will swab volunteers at the event to register them in the network.
Bobbylynn Stewart with Breck Construction, the title sponsor for the event, said she has a personal stake in helping organize the run because her mother also died of acute myeloid leukemia. Its a chance for the company and the community to help other families with similar struggles, she said.
When you have a blood cancer or disorder, often times you are relying on a stem cell match through the network, Stewart said. So growing that network is vital.
Alongside the run will be a charity silent auction and a barbecue. Mandis brothers, professional hockey players Jayden and Rylan Schwartz, are also expected to attend, along with NHL players Ryan Murray and JC Lipton, and AHL player Brandon Gormley.
Erica Honoway, scheduled to speak before the run, said she is haunted by how close her family came to sharing in the Schwartzs tragedy.
Her son Lincoln was diagnosed with aplastic anemia last year, but a bone marrow transplant helped save his life.
In all the registries in the world, they found two matches for Lincoln, Honoway said. Every single person who gets on is another chance for someone to have their life saved.
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Annual 'Run for Mandi' hosting bone marrow registry to combat cancer - Saskatoon StarPhoenix
Bowl-A-Thon For Stem Cell Bone Marrow Transplant Recipients – BlackburnNews.com
By LizaAVILA
Madalayna and Tamara Ducharme, 33 days after Madalayna received her bone marrow transplant. Photo provided by Tamara Ducharme) By Adelle LoiselleAugust 25, 2017 5:10am
Six months ago, Windsor residents came out in droves to help baby Madalayna Ducharme find a bone marrow match.
Saturday, they can help again by taking part in a bowl-a-thon dedicated to supporting the families of those who still need a transplant.
The 12th annual Bowling for Bone Marrow Bowl-a-Thon takes place Saturday at Rose Bowl Lanes on Dougall Ave. in Windsor. Check-in is at noon, and the fundraiser gets underway at 1pm.
It is the Katelyn Bedard Bone Marrow Associations biggest fundraiser of the year, and this year it can count Madalayna among its success stories.
The baby girl, who celebrated her first birthday this week, likes to dance and can stand while holding her parents fingers. Her mother, Tamara Ducharme is grateful for every day.
We were unsure if we were going to make it there, to the first birthday, she says. Were hoping that shell be a healthy little girl.
However, the struggle is not over. Friday, the family is driving up Hwy. 401 for Madalaynas six-month post-transplant appointment at Sick Kids Hospital in Toronto.
Ducharme says her daughter has bi-weekly hospital visits to ensure her medication is up to date. Madalayna still uses a feeding tube, and even months later, there is still the question whether the bone marrow transplant from her brother is working.
Theyll probably do an x-ray, says Ducharme about the upcoming appointment. Shes had a little growth. If her bones show changes that means shes on the track of getting better. Now, if there is no change, I dont know what were going to do.
Life with a young child who has received a transplant can also be very isolating, and Ducharme admits it has not been easy.
Were bubbled. We really go anywhere. We dont really play with other kids, she says. Youve gotta take the proper steps to take care of your child. If she could catch anything and it could be really detrimental.
She says the association has been very good to her family and they are grateful for their, and the communitys support over a challenging chapter in their lives.
Bryan and Joanne Bedard understand the difficulties faced by families of children waiting for a donor. They lost their three-year-old daughter, Katelyn in 2005 at the age of 3 when they were unable to find one.
Since then, they have raised money for donor clinics and awareness of the OneMatch Stem Cell and Marrow Network which now has 6,500 registered donors. The Katelyn Bedard Bone Marrow Association has also donated $115,000 to stem cell and bone marrow transplant research at both the University of Windsor and the Universite de Montreal.
With files from Maureen Revait
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Bowl-A-Thon For Stem Cell Bone Marrow Transplant Recipients - BlackburnNews.com
‘I approached my 50th birthday unable to balance or speak’ – Telegraph.co.uk
By NEVAGiles23
I didnt want it to affect my job as a BBC correspondent covering religious affairs. But in 2015 I went numb down one side of my body for several weeks. A scan showed multiple lesions, and a specialist confirmed I had relapsing-remitting MS. It felt like a life sentence. My family wasnt surprised wed long known it was a possibility. No tears were shed; my parents are of the stiff-upper-lip generation.
The next drug failed to stop another relapse. I wanted to keep reporting for as long as possible, but last September I finally stepped down frommy job, and my bosses helped me find other options involving less travel and with more predictable hours.
My MS seemed to be moving from relapsing-remitting to secondary progressive, as my body became less able to repair the brain damage caused by each relapse. So, after months of research, I decided to take a risk and have an autologous hematopoietic stem cell transplant (HSCT) a chemotherapy treatment that wipes out then regrows your immune system at a private clinic in Mexico.
HSCT has long been used to treat blood cancers, but its use in autoimmune diseases like MS is still undergoing trials. It destroys the malfunctioning cells thought to be responsible for damaging the myelin sheath, while stem cells harvested from your bone marrow are given back to shorten your time without a working immune system.
HSCT holds the most promise for people having regular MS attacks and its now offered to some MS patients at a few NHS hospitals in England under tight criteria. I didnt qualify, but I met several others who had been helped by it.
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'I approached my 50th birthday unable to balance or speak' - Telegraph.co.uk
After treatment for serious illness, NBC-5 anchor Rob Stafford returning to air – Chicago Tribune
By daniellenierenberg
NBC-5 News anchor Rob Stafford will return to the air Monday, after months of grueling treatment for a rare blood disorder that gave him a harrowing look at "my own mortality."
"I thought we'd get this thing nipped in the bud," said Stafford, 58, who took a leave of absence in March after being diagnosed to be in the early stages of amyloidosis.
Instead, Stafford said, he spent much of the last six months too sick to eat, drink or walk while learning that the road back to health from serious illness is a process.
"You learn that everybody reacts to these drugs differently and there is no guarantee of any outcome," he said.
Amyloidosis occurs when abnormal protein called amyloid is produced in bone marrow and can be deposited in tissues and organs. There are more than 40 types of the disorder that affect the heart, kidneys, liver, spleen, nervous system and digestive tract. Stafford's type known as light chain amyloidosis is rare, according to Dr. Ronald Go, Stafford's hematologist at the Mayo Clinic in Rochester, Minn.
Doctors had planned to remove or "harvest" stem cells from Stafford's own bone marrow and freeze millions of healthy ones. After wiping out the unhealthy cells using chemotherapy, Stafford was to have the healthy stem cells transplanted back into his bone marrow, where they were to reproduce themselves, Go said in March.
Zbigniew Bzdak/Chicago Tribune
Rob Stafford, shown Aug. 24, 2017, is planning to return to the anchor desk at NBC-5 News on Aug. 28 after months battling amyloidosis.
Rob Stafford, shown Aug. 24, 2017, is planning to return to the anchor desk at NBC-5 News on Aug. 28 after months battling amyloidosis. (Zbigniew Bzdak/Chicago Tribune)
But Stafford ran into several complications immediately after the transplant process began that forced him to remain hospitalized for most of March.
"There were times in the hospital when I thought he might not make it," said his wife, Lisa Stafford, who would jog around the Rochester area to alleviate her stress.
"On the runs, I would stop at every church to pray and light a candle."
Stafford returned to his home in Hinsdale in early April, too weak sometimes to walk across the room, drink a milkshake or even stay awake for the news, he said.
In June, test results showed the bone marrow transplant did not work as they had planned, and Stafford would need a new course of action to fight the disease, he said.
It was a terrifying place to be, Stafford said.
"You think, 'What if nothing works?'" he said. "I have clearly thought about my own mortality."
Doctors at Rush University Medical Center started Stafford on a new regimen of weekly chemotherapy, which dramatically improved his health. While he has not yet reached the low amyloid measurements that define remission, doctors are optimistic about his recovery and have cleared Stafford to return to work, he said.
Stafford will return to the 10 p.m. news. Dick Johnson and Patrick Fazio will share anchoring duties with Allison Rosati at 5 p.m. and 6 p.m. until Stafford is ready to return to those newscasts, said Frank Whittaker, station manager and vice president of news for NBC Chicago.
"We are eagerly looking forward to Rob's return on Monday night," Whittaker said in an email. "He has inspired all of us with his courage and determination over the past six months. It will be great to have him back in our newsroom."
Stafford said he remains grateful for the support he and Lisa felt from viewers, who sent him a steady stream of Facebook messages, cards and personal stories.
"It's like running a marathon, and there are all these people along the side cheering you on," Stafford said. "It helps you get through it."
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After treatment for serious illness, NBC-5 anchor Rob Stafford returning to air - Chicago Tribune
Family of Mandi Schwartz connecting donors with stem cell network – Globalnews.ca
By Dr. Matthew Watson
The parents of a Saskatchewan-born Yale University hockey player are trying to connect more people with a bone marrow and stem cell network that could save lives.
Rick and Carol Schwartz will be in Saskatoon on Sunday for the sixth annual Run for Mandi named after their daughter Mandi Schwartz, who was diagnosed with acute myeloid leukemia in December 2008 and died in April 2011.
READ MORE: Could you save his life? Edmonton boy needs to find stem cell match
Officials from the OneMatch Stem Cell and Marrow Network, part of Canadian Blood Services, will take swabs from volunteers in hopes of connecting donors with patients who need stem cell transplants.
Its the first time the event will have on-site registration for the network.
Fewer than 25 per cent of people find a stem cell donor in their family and only 50 per cent find a match in the international network of donors, according to Blood Services.
Mandi never found one.
It was frustrating to know that. Its almost like we let her down, Rick Schwartz said.
In 2010, his daughter penned a letter, stating her hope that doctors would find her a life-saving match. She also hoped to increase the donor registry to help others.
If someone else in Mandis family needed a stem cell transplant, she wouldve been the first person to help out, her mother said.
I just know she would be front and centre in leading a drive if she were with us today, Carol Schwartz said.
Another registration drive in Mandis name happens annually at Yale University. So far, more than 6,000 people have registered and 37 have resulted in stem cell matches.
Ideal candidates are between the ages of 17 and 35 and meet certain health criteria.
If a person registers and matches with a person in need, its usually as easy taking blood, according to Run for Mandi co-organizer Bobbylynn Stewart.
Fifteen per cent of the time, they do require your bone marrow, said Stewart, who lost her mother to acute myeloid leukemia.
They go in through your hip and draw it through there, so its under anesthesia. Its about an hour-long process.
READ MORE: Run for Mandi raises over $20K for memorial bursary funds
Sundays event lasts from 1 p.m. to 4 p.m. and running isnt required.
Lincoln Honoway, who was three when he was admitted to Regina General Hospital last year with dangerously low blood counts, will be in attendance.
After finding a stem cell transplant, Lincolns blood cell counts have started to rise and stabilize.
The run is planned for River Landing, with pro hockey players Ryan Murray, JC Lipon and Brandon Gormley expected to be there.
Mandis brother, Jaden Schwartz of the St. Louis Blues, will attend as well.
2017Global News, a division of Corus Entertainment Inc.
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Family of Mandi Schwartz connecting donors with stem cell network - Globalnews.ca
Buckeye Be The Match set for Saturday – Piqua Daily Call
By daniellenierenberg
TROY The second annual Buckeye Be The Match will build on its opening year by adding bikes to the event while raising awareness for bloodborne cancers this Saturday.
The Buckeye Be The Match will begin at 8 a.m. Aug. 26, at Treasure Island Park. New this year is a 15-mile and 50-mile bike route in addition to the 5K and 1K Fun Run in the park.
The event added the 15-mile family bike ride north to Piqua and back to Treasure Island as well as a more challenging 50-mile ride throughout the county to expand the use of the nearby bike paths to include cyclists of all levels. Bikers may begin to ride as early as 7:30 a.m. Saturday.
Online registration ends on Thursday, but registration in person will continue through 8 a.m. Saturday at the park. Opening events kick off at 9 a.m. All proceeds benefit the Be The Match organization, which helps build a national registry to find potential donors through a simple cheek swab.
The funding goes to Be The Match, which is dedicated to finding the bone marrow matches or stem cell matches for those with blood born cancers. It is very vital, said city council member Tom Kendall. If you dont want to run or be part of the bike ride, you do have the opportunity to save a life also. They will be taking swabs of those who would like to be put on the registry to be a potential donor for a person in need.
Kendall said Rum River Blend will provide entertainment as well as family-friendly activities through noon. There also will be a ceremony featuring the Be The Hero award, which nominates someone who has helped a survivor during their treatment and will be given out at the event.
Kendalls daughter, Lisa, was diagnosed at 28 with acute myeloid leukemia in 2011. She received a stem cell transplant that saved her life. Shes been a coordinator of the event and advocate for the Be The Match organization since it moved to Troy last year from Columbus.
Kendall said previous the Buckeye Be The Match raised more than $11,000 last year, exceeding its goal of $10,000.
For more information, visit http://www.bethematchfoundation.org.
Event to raise funds and awareness for bone marrow registry
Follow Melanie Yingst on Twitter @Troydailynews
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Buckeye Be The Match set for Saturday - Piqua Daily Call
Archbishop Derderian Leads Prayers for ABMDR Patients at Diocese Churches – Asbarez Armenian News
By daniellenierenberg
The ABMDR team at the meeting with Archbishop Hovnan Derderian (center) and the Very Rev. Fr. Dajad Yardemian.
LOS ANGELESOn Sunday, August 20, during Holy Mass at St. Leon Cathedral in Burbank, Archbishop Hovnan Derderian, Primate of the Western Diocese, offered special prayers for patients of the Armenian Bone Marrow Donor Registry (ABMDR). In his sermon, the Archbishop praised the life-saving mission of ABMDR, and called on congregants to continue to support its work.
To raise public awareness of the ABMDR mission and encourage grassroots involvement in the organizations activities, the Western Diocese has observed a special Prayer Day in honor of ABMDR patients for the past several years. The Prayer Day is marked at St. Leon Cathedral as well as Armenian churches across Southern California.
In the course of his sermon on August 20, Archbishop Derderian stated that participating in the work of ABMDR is tantamount to praying and accomplishing a Godly mission. The Archbishop pledged the continuous support of the Diocese and appealed to all parishes to embrace the work of ABMDR, by joining its ranks as potential bone marrow stem cell donors, signing up as volunteers, and attending its public-benefit events such as the upcoming Match for Life, the ABMDRs 18th annual Gala, which will be held on Sunday, August 27, in Los Angeles.
The ABMDR team outside St. Leon Cathedral
Archbishop Derderian, who is one of ABMDRs most avid and longtime supporters, exemplifies the type of leadership that works tirelessly for the well-being of our community, said ABMDR president Dr. Frieda Jordan. We are honored and grateful for the Primates ongoing guidance and support.
Following the church service, numerous parishioners had the opportunity to become more familiar with the activities of ABMDR, as a team of Board members and volunteers from the organization answered questions and handed out information about becoming donors.
Subsequently Archbishop Derderian, along with the Very Rev. Fr. Dajad Yardemian, met with the ABMDR team at the Diocese. The discussion centered on ABMDRs most recent achievements as well as its plans for the immediate future. At the conclusion of the meeting, Archbishop Derderian presented scarves from Holy Echmiadzin to all members of the ABMDR team, as tokens of his appreciation.
Established in 1999, ABMDR, a nonprofit organization, helps Armenians and non-Armenians worldwide survive life-threatening blood-related illnesses by recruiting and matching donors to those requiring bone marrow stem cell transplants. To date, the registry has recruited over 29,000 donors in 42 countries across four continents, identified over 4,190 patients, and facilitated 30 bone marrow transplants. For more information, call (323) 663-3609 or visit abmdr.am.
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Archbishop Derderian Leads Prayers for ABMDR Patients at Diocese Churches - Asbarez Armenian News
Vitamin C May Help Slay Blood Cancer Stem Cells – Anti Aging News
By LizaAVILA
Vitamin C may prompt faulty stem cells in bone marrow to die off, rather than multiplying to spur blood cancers.
A new study has found that vitamin C may communicate to faulty stem cells within bone marrow that they should mature and perish in a normal manner rather than multiplying to spur blood cancers. This is the insight gleaned from a study spearheaded by NYU Langone Health Perlmutter Cancer Center researchers. Study details were recently published in Cell.
About the Findings
The authors of the study state specific genetic alterations are known to decrease the ability of an enzyme referred to as tet methylcytosine dioxygenase 2 (TET2) to promote stem cell maturation and death in patients who have specific types of leukemia. They determined vitamin C activates TET2 functionality in mice designed to lack the enzyme. It is possible that vitamin C will prove to be a safe and effective treatment for diseases spurred by leukemia stem cells deficient in TET2. It is likely that vitamin C will be used in combination with other targeted therapies.
Study Details
The researchers used genetically altered mice in which TET2 was turned off. These mice endured abnormal stem cell activity. Such changes were reversed when a genetic trick restored TET2 expression. Providing high doses of vitamin C functioned similarly to restoring TET2 functionality on a genetic level. Vitamin C's promotion of DNA demethylation caused stem cells to mature and limited the advancement of leukemia cancer stem cells from humans that were implanted in mice. Vitamin C treatment affected leukemic stem cells similar to damaged DNA. Vitamin C was used in combination with a PARP inhibitor to produce an enhanced effect on such stem cells, sending them from self-renewal to maturity and subsequent death.
TET2 and Cancer
Alterations in the genetic code that decrease TET2 functionality are found in 10% of those who have acute myeloid leukemia (AML). About one-third of patients with a form of preleukemia known as myelodysplastic syndrome and upwards of half of those with chronic myelomonocytic leukemia have such genetic code mutations. These cancers spur anemia, bleeding and infection risk as abnormal stem cells multiply within bone marrow until they block the production of blood cells. Recent tests show about 2.5% of cancer patients living in the United States might develop TET2 alterations. This includes some patients with solid tumors and lymphomas.
About Cell Death Switch
The results of the study center on the relationship between cytosine and TET2. Cytosine is one of the several letters of nucleic acidthat make up genes' DNA code. Each cell type has thesame genes yet each receives unique instructions to turn on only those required in a specific cellular context. Examples of such epigenetic mechanisms include DNA methylation. This is an attachment of a diminutive molecule to cytosine bases to put a halt to the action of a gene containing them. Gene expression within stem cells is fine-tuned when methyl groups are attached and removed. Stem cellexpressions can then mature and multiplyto form muscle, nerve, bone and other types of cells. The bone marrow holds stem cell pools as adulthood is reached until they can become replacement cells. Inpatients with leukemia, signals that typically tell blood stem cells to mature end up malfunctioning. This allows for endless multiplication and a self-renewing rather than the generation of regular white blood cells required to combat infection.
TET2 empowers an alteration in the molecular structure of methyl groups required for their removal from cytosines. Such demethylation activates genes that direct stem cells to mature and commence a countdown to self-destruction as a component of regular turnover. This functions as a means of combating cancer yet it is disrupted in blood cancer patients who have TET2 mutations.
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Vitamin C May Help Slay Blood Cancer Stem Cells - Anti Aging News
VistaGen’s cell production methods receive US patent boost – BioPharma-Reporter.com
By raymumme
VistaGen Therapeutics has received a notice of allowance for a stem cell production patent, which the firm says could be used in autoimmune disorder and cancer treatments.
The US Patent and Trademark Office (USPTO) issued VistaStem a subsidiary of VistaGen the notice for patent no. 14/359,517, which covers methods for producing hematopoietic precursor stem cells usually found in red blood marrow.
These are stem cells that give rise to all of the blood cells and most of the bone marrow cells in the body, with potential to impact both direct and supportive therapy for autoimmune disorders and cancer, said VistaGen VP Mark McPartland.
With CAR-T cell applications and foundational technology, McPartland said he believed the technology will provide approaches for producing bone marrow stem cells for bone marrow transfusions.
Business opportunities
In December last year, VistaGen signed an exclusive sublicense agreement with stem cell research firm BlueRock Therapeutics, under which the latter paid VistaGen $1.25m (1.06m) upfront for its cardiac stem cell production technologies.
McPartland said he expects this recent notice of allowance to also create potential opportunities for additional regenerative medicine transactions.
IP portfolio growth
VistaGen told us it plans to secure IP protection in multiple domains and international jurisdictions.
We intend to grow our IP portfolio in a manner that emphasises platform protection and maximises opportunities for commercialisation and out-licensing, McPartland said.
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VistaGen's cell production methods receive US patent boost - BioPharma-Reporter.com
Howard University Hosts ‘Be The Match’ Marrow Registry Drive – Howard Newsroom (press release)
By raymumme
Howard University Hospital's Dr. Ermias Aytenfisu seeks to clear up misconceptions about marrow donation in the minority community.
WASHINGTON, D.C. (August 21, 2017) Elsa Nega is an Ethiopian-Canadian mother of two young children. She loves her children and wants to watch them grow. However, Nega has a rare form of blood cancer, leukemia, and needs a bone marrow transplant to survive.
Black patients like Nega are the least likely to find their suitable blood marrow match, according to Be The Match which is hosting a Stem Cell/Bone Marrow registry event at the Howard University College of Medicine on Wednesday, Aug. 30 between 11 a.m. and 3 p.m. The exact location for the registry drive is the lobby outside of room 1008 in the Numa P. Adams building.
Negas story began in February when she walked into her local ER and was rushed to intensive care. By the next morning Nega was diagnosed with Acute Lymphoblastic Leukemia (ALL) and started on chemo immediately. Unlike 90 percent of patients who go into remission after the first round of chemo, she did not.
Now, after three rounds of chemo, a bone marrow transplant is her only hope of recovery. Negas siblings were not a match and she is reaching out to the Washington region because of its large population of people of Ethiopian descent.
There are a lot of myths associated with marrow donation, said Amanda Holk, community engagement representative with the Be The Match in Washington, D.C. There is so much fear surrounding the process but most donors are back to work the next day.
ErmiasM. Aytenfisu, M.D., stroke medical director at Howard University Hospital said the most common way to donate bone marrow is through a procedure called peripheral stem cell donation. No surgery is involved. Donors receive medication to increase peripheral stem cells before the donation. On the day of donation, blood is removed through a needle on one arm and passed through a machine that separates out the blood-forming cells. Uncommonly marrow donation involves surgical techniques that use a special needle to take out blood forming cells. During the procedure, the patient is anesthetized and feels no pain.
Joining the bone marrow registry at the Howard University College of Medicine event involves a simple as a cheek swab and an application. A persons chance of being a match at that point is only 1 in 500. But, for a patient like Elsa, you could be the only one. Elsa does not have a single match on the registry although there are 30 million people signed up.
For more information, contact Amanda Holk via email AHolk@nmdp.org or 202-875-9987
For the Howard University registry drive, please note that you must be between the ages of 18 and 44 to join the registry since research has shown that the younger the cells, the better the patient outcomes. And the following conditions prevent you from joining:
Hepatitis B or C
HIV
Organ, marrow or stem cell transplant recipient
Stroke or TIA (transient ischemic attack)
Other upcoming local events to support Elsa Nega:
*Empower the community (The Helen Show)
Date: 08/26/2017 (Sat.)
Location: Washington Convention Center
*Ethiopian Day Festival
Date: 09/03/2017 (Sun.)
Location: Downtown Silver Spring
About Howard University Hospital
Over the course of its roughly 155-year history of providing the finest primary, secondary and tertiary health care services, Howard University Hospital (HUH) remains one of the most comprehensive health care facilities in the Washington, D.C. metropolitan area and designated a DC Level 1 Trauma Center. The hospital is the nation's only teaching hospital located on the campus of a historically Black university. For more information, visit huhealthcare.com
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Howard University Hosts 'Be The Match' Marrow Registry Drive - Howard Newsroom (press release)
Winnipeg man to donate stem cells to critically ill stranger in Israel – CBC.ca
By raymumme
When Alex Shorheardthat he was a match for a stranger in Israel who would likely die without a stem cell transplant, he didn't think twice before saying "yes."
"If I today I help somebody, tomorrow I want somebody to help me too if I [am] sick," said Shor. "I don't think too much about it."
The request came from Ezer Mizion, an Israeli health service with the world's largest Jewish bone marrow registry, countingover 850,000 registrants worldwide. Shor said the representative told him the recipient would be a63-year-old man in Israel.
Shor, 41, had registered his DNA with the registry 10 years ago when he lived in Israel.
Shor and his family emigrated to Winnipeg nearly three years ago. In March, he got word that his stem cells were a match.
Stem cells are immature blood cells that can grow into healthy cells. They can make the difference between life and death for people with various forms of cancer, blood-related illnesses and metabolic disorders.
Shorwas agenetic match for the man based on the human leukocyte antigen (HLA) system, which codes the human immune system. The pair would have had to have 10 of the same HLA markers to be a viable match.
In May, Shorwent to a lab in Winnipeg to draw blood to send off to Israel to ensure hisblood would be compatible with the recipient's. Now, he plans to travel to Israel to donate his stem cells as soon as he hears from the physicians that the patient's condition has improved enough to tolerate the procedure.
Getting Shor's blood to Israel required a cooler, a courier and some creativity.
Vials of Shor's blood were transported to Israel in an ice-packed Thermos.
Dena Bensalmon, Canadian director of Israeli health service Ezer Mizion, put out a call on Facebook for a chaperone that could transport five vials of Shor's blood.
"Sixteen people came forward within about four minutes," she said.
One woman the perfect candidate was travelling from Winnipeg to Toronto, then on to Isreal. They packed the blood in ice in a Coleman thermos for the 12-hour journey.
"I met Dina in Toronto and then I switched the ice packs. They took the blood directly," she said.
Canada'sOneMatchregistry through Canadian Blood Serviceshas about 400,000 registrants.
But"if a person is Jewish, then the chances of them finding their match on a Jewish registry is far greater than them finding their match on a non-Jewish registry," saidBensalmon.
Canadian Blood Services has access to nearly 29 million volunteer donors and more than 720,000 cord blood units from dozens of countries around the world, as all the registries are connected under the umbrella of the World Marrow Donor Association, comprised of millions of people from across the world.
"I find the whole thing almost like watching a circle of life," said Bensalmon.
A volunteer brought vials of Shor's blood to Israel. She kept the thermos in her lap the whole 12-hour trip.
Shor said he just thought of his own father and how he would want someone to help him if he had a life-threatening illness. He encourages everyone to join a stem-cell registry.
"Tomorrow you may save somebody and tomorrow you don't know if you be sick and somebody save you," said Shor.
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Winnipeg man to donate stem cells to critically ill stranger in Israel - CBC.ca
The power of vitamin C: Can it kill cancer stem cells? – Bel Marra Health
By daniellenierenberg
Home Cancer The power of vitamin C: Can it kill cancer stem cells?
Every three minutes, one person in the United States is diagnosed with blood cancer. Thankfully, there may be a new approach to helping these individuals fight it using vitamin C.
Researchers from Perlmutter Cancer Center at NYU Langone Health recently published a report in the journal Cell indicating that vitamin C may be able to tell faulty cells in bone marrow to mature and die instead of multiplying to cause blood cancers. They explained that specific genetic changes are able to reduce the ability of the enzyme known as TET2 to push stem cells to mature, which die in many people who suffer from leukemia. Experts discovered that vitamin C seemed to activate TET2 in mice that were engineered to be TET2 deficient. In simple terms, TET2 is a tumor suppressor that can prevent certain cells from growing uncontrollably.
Mutations that reduce TET2 function are present in about 10 percent of people with acute myeloid leukemia, 30 percent of patients with a pre-leukemia known as myelodysplastic syndrome, and close to 50 percent of people with chronic myelomonocytic leukemia. Tests indicate that about 2.5 percent of U.S. cancer patients develop TET2 mutations, including some with lymphomas.
The study focused on the relationship between TET2 and cytosine, which is one of four nucleic acid letters that make up the DNA codes in our genes. The attachment of a small molecule, referred to as a methyl group, to cytosine bases can shut down the actions of a gene. As the human body forms, the attachment and removal of methyl groups adjust gene expression in stem cells, which can mature and become muscle, bone, nerve, or other cell types. The bone marrow keeps stem cells in pools, ready to become replacement cells when and if needed. In the case of leukemia, the signals that are supposed to tell a blood stem cell to mature end up malfunctioning, leaving it to multiply instead of developing normal white cells, which are needed to help fight infection.
Medical scientists explain that TET2 allows for a change in methyl groups that are required to be removed from cytosine. This essentially turns on genes and directs stem cells to mature and eventually destroy themselves. Researchers say that this signals an anti-cancer mechanism, something that can help blood cancer patients with TET2 mutations.
The team of researchers genetically engineered mice to manipulate the TET2 gene. Techniques to turn off TET2 in mice lead to abnormal stem cell behavior. The changes were reversed when TET2 was restored. Since previous work indicated that vitamin C could stimulate TET2, the researchers theorized that high doses of vitamin C might reverse the effects of TET2 deficiency. It would be a case of turning up the action on the functional gene. As it turns out, high dose vitamin C treatment did induce stem cells to mature and also suppressed the growth of leukemia cancer cells implanted in mice.
As of now, the NYU team is working on identifying genetic changes that may contribute to the risk of leukemia in specific groups of patients. While this latest study provides some hope for blood cancer patients, the manipulation of TET2 is only a potential new treatment approach until further studies are conducted. Currently approved treatments for blood cancers include stem cell transplantation, chemotherapy, and radiation therapy.
Related: Combining antibiotics and vitamin C helps to combat cancer stem cells
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http://www.cancercenter.com/terms/blood-cancers/https://ghr.nlm.nih.gov/gene/TET2
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The power of vitamin C: Can it kill cancer stem cells? - Bel Marra Health