SAN CARLOS, Calif., March 1, 2017 /PRNewswire/ --Natera (NTRA), a leader in genetic testing, today announced the upcoming launch of Evercord; a new offering being made commercially available in the second quarter of 2017 that enables expectant parents to collect, store and potentially retrieve their newborn's cord blood and tissue for therapeutic use in transplantation and regenerative medicine applications. Natera aspires to build a different type of national cord blood company, by combining best-in-class cord blood cryopreservation with the company's ability to provide timely information about genetic disease risk; potentially expanding families' stem cell treatment options in the future. Natera will offer Evercord through its leading direct sales channel in the United States.

The Market Potential of Cord Blood Stem Cells Newborn stem cells sourced from umbilical cord blood are known to contain hematopoietic stem cells (HSCs) that can potentially differentiate and regenerate healthy blood and immune systems. Unfortunately, out of the roughly four million births each year in the United States, more than 95% of the cord blood from those births is currently discarded as waste;1 highlighting a significant opportunity both for families who could benefit from cord blood, and for Natera, as it enters the cord blood and tissue banking market. Published data also suggests that one in three people in the United States, or 128million people, could potentially benefit from regenerative medicine applications which, if proven effective, expands the possible therapeutic use of cord blood stem cells.2 More than 300 studies are currently underway, including clinical trials focused on current and new cord blood stem cell therapies in regenerative medicine.3 These trials hold promise for a growing list of conditions, including Alzheimers disease, cerebral palsy, diabetes (Type I/II), spinal cord injury, cartilage and bone repair, and heart defects. More than 30,000 cord blood stem cell treatments have been conducted worldwide and Natera's prenatal tests, including its carrier test, Horizon, currently screen for 35 of the nearly 80 diseases where cord blood stem cell treatment has been administered. Considering the research advances in stem cells and regenerative medicine, it is anticipated that number will, more than likely, continue to grow.

Introducing EvercordThe launch of Evercord is part of a partnership with Bloodworks Northwest, one of the oldest and most reputable public umbilical cord blood banks in the country. Evercord's service will offer expectant families the opportunity to bank their baby's umbilical cord blood and tissue for potential medical use by the child or related family member. Under the terms of the agreement between Natera and Bloodworks, Bloodworks will perform processing and testing services on cord blood samples submitted by Evercord customers and will cryo-preserve the banked cord blood and tissue at its Seattle, Washington-based best-in-class cord blood cryopreservation storage facility. The companies also plan to build a new facility in anticipation of future growth.

The relationship offers several other competitive advantages. Evercord leverages Bloodworks' 20 years of experience processing and banking cord blood; the lab has a strong track record of successfully releasing nearly 1,000 cord blood samples for transplant, more than other leading private cord blood banks.

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Once Evercord is commercially launched, it will expand Natera's existing portfolio of women's reproductive health products, further diversifying Natera's revenue base and adding a traditionally high yield business into its product mix. Evercord will also be well positioned to immediately take advantage of Natera's well-established commercial capabilities, including: patient and healthcare provider digital services through Natera's Patient Portal and Natera Connect, and a specialized salesforce that already calls on the nation's busiest obstetrics and gynecology offices and fertility centers.

"At Natera, we believe adding cord blood and tissue banking to our product offerings is a natural extension of our commitment to family health and beyond," said Matt Rabinowitz, CEO and founder of Natera. "Evercord builds on our excellence as a genetic testing company and our mission to transform the diagnosis and management of genetic diseases. Cord blood stem cells have demonstrated regenerative capabilities that medicine is just beginning to learn how to harness; offering a unique opportunity to potentially generate complete genetic information on a human being at the moment of birth. Many of the genetic diseases that cord blood treats today are also conditions that our tests screen for, which could enable us to offer a far more extensive service offering in the future than those offered by leading 'storage-only' cord blood banks today."

About Bloodworks Northwest's Public Cord Blood ProgramBloodworks Northwest partners with hospitals across the region to recover and store umbilical cord blood from new mothers -- an important source of stem cells for use in cancer treatment, metabolic or immune system disorders, and research. Bloodworks Northwest created the first and only public umbilical cord blood bank in the Northwest of the United States and has program partnerships with 15 hospitals across Washington, Oregon and Hawaii providing nearly 50 units per month to the national cord bloodregistry.

About NateraNatera is a genetic testing company that develops and commercializes non-invasive methods for analyzing DNA. The mission of the company is to transform the diagnosis and management of genetic disease. In pursuit of that mission, Natera operates a CAP-accredited laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA) in San Carlos, CA, and it currently offers a host of proprietary genetic testing services primarily to OB/GYN physicians and fertility centers, as well as to genetic laboratories through its cloud-based Constellation software system.

Product offerings include the Spectrum pre-implantation genetic test for embryo selection during IVF; the Anora miscarriage test to understand the genetic causes of a pregnancy loss; the Horizon carrier test to detect inherited mutations; the Panorama non-invasive prenatal test (NIPT) to identify common chromosomal anomalies in a fetus as early as nine weeks of gestation; and Evercord, a cord blood and tissue banking service offered at birth to expectant parents.

Each test described has been developed and its performance characteristics determined by the CLIA-certified laboratory performing the test.

These tests have not been cleared or approved by the U.S. Food and Drug Administration (FDA). Although FDA does not currently clear or approve laboratory-developed tests in the U.S., certification of the laboratory is required under CLIA to ensure the quality and validity of the tests.

Natera is also applying its unique technologies to develop non-invasive screening and diagnostic tools for earlier detection and improved treatment of cancer. These tests have not been cleared or approved by the U.S. Food and Drug Administration.

Forward-looking statementsThis release contains forward-looking statements. All statements other than statements of historical facts contained in this press release are forward-looking statements. Any forward-looking statements contained in this press release are based upon Natera's historical performance and its current plans, estimates, and expectations, and are not a representation that such plans, estimates, or expectations will be achieved. These forward-looking statements represent Natera's expectations as of the date of this press release.

Subsequent events may cause these expectations to change, and Natera disclaims any obligation to update the forward-looking statements for any reason after the date of this press release. These forward-looking statements are subject to a number of known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to our efforts to develop and commercialize new product offerings, our ability to successfully increase demand for and grow revenues for our product offerings, whether the results of clinical studies will support the use of our product offerings, whether cord blood or cord tissue will be found to be effective in treating additional conditions, our expectations of the reliability, accuracy and performance of our screening tests, or of the benefits of our screening tests and product offerings to patients, providers and payers.

Additional risks and uncertainties are discussed in greater detail in the sections entitled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" in Natera's Form 10-Q for the quarter ended September 30, 2016. Further information on potential risks that could affect actual results will be included in other filings Natera makes with the SEC from time to time. These documents are available for free on the company's website at http://www.natera.com under the Investor Relations section, and on the SEC's website at http://www.sec.gov.

Contacts:Natera, Inc. Mike Brophy, Chief Financial Officer, 650-249-9091 x1471 mbrophy@natera.com Laura Zobkiw, Corporate and Media Relations, 650-249-9091 x1649 Lzobkiw@natera.com

1https://parentsguidecordblood.org/en/cord-blood-infographic (February 2017). 2 Harris, D., & Rogers, I. (2007). Umbilical Cord Blood: A Unique Source of Pluripotent Stem Cells for Regenerative Medicine.Current Stem Cell Research & Therapy,2(4), 301-309. doi:10.2174/157488807782793790; http://www.mdpi.com/2227-9059/2/1/50/htm 3https://clinicaltrials.gov/ct2/results?term=Umbilical+AND+Stem+Cells (February 2017).

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Natera, Inc. Announces Launch of Evercord Cord Blood and Tissue Banking Service - Yahoo Finance

Spinal Cord Stem Cells Comments Off on Natera, Inc. Announces Launch of Evercord Cord Blood and Tissue Banking Service – Yahoo Finance | March 1st, 2017

MOUNTAIN VIEW, Calif.--(BUSINESS WIRE)--

SanBio, Inc., a scientific leader in regenerative medicine for neurological disorders, today announced that a recent publication of its novel stem cell treatment, SB623, for patients following a stroke, has received a prestigious award from the American Heart Association. The scientific article, Clinical Outcomes of Transplanted Modified Bone Marrow-Derived Mesenchymal Stem Cells in Stroke: A Phase 1/2a Study, was the third prize winner of the 2016 Stroke Progress and Innovation Award.

The Progress and Innovation Awards are offered by Stroke, a leading scientific journal addressing the diagnosis and treatment of cerebrovascular diseases, jointly with the American Heart Association and American Stroke Association. Previous award winners have established important standards of care in neurology, including Activase (alteplase) and induced hypothermia treatment.

Dr. Damien Bates, Chief Medical Officer and Head of Research at SanBio, said, This prize from the American Heart Association recognizes the innovation of our stem cell treatment, SB623, and its potential to treat patients suffering from chronic physical impairments following ischemic stroke. The results of this study are encouraging to all those suffering from the long-term effects of stroke as well as the medical community working to advance treatment options.

The clinical trial was a Phase 1/2a, open-label, single-arm, dose escalation study of 18 patients with chronic motor deficits present for at least six months following an ischemic stroke. Patients received precisely targeted injections of SB623 cells directly into the neural tissue surrounding the damaged area of the brain.

Dr. Gary Steinberg, Chairman of the Department of Neurosurgery at the Stanford University School of Medicine and Co-Director of the Stanford Stroke Center, served as Principal Investigator for the clinical trial.

Results for subjects who completed the single arm Phase 1/2a study demonstrated statistically significant improvement in motor function, evaluated using the European Stroke Scale, National Institutes of Health Stroke Scale, the Fugl-Meyer total score and the Fugl-Meyer motor function total score. The data also showed that the treatment was generally safe and well-tolerated by the trial participants.

As lead author of the scientific article, Dr. Steinberg accepted the award at the recent International Stroke Conference in Houston.

About SanBio, Inc. (SanBio)

SanBio is a regenerative medicine company headquartered in Tokyo and Mountain View, California, with cell-based products in various stages of research, development and clinical trials. Its proprietary cell-based product, SB623, is currently in a Phase 2b clinical trial for treatment of chronic motor impairments resulting from stroke, with its joint development partner, Sumitomo Dainippon Pharma Co., Ltd., in the United States and Canada. SanBio is also implementing a global Phase 2 clinical trial using SB623 in the United States and Japan for the treatment of motor impairment resulting from traumatic brain injury. More information about SanBio is available at http://www.sanbio.com.

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Study of SanBio's Stem Cell Treatment for Stroke Receives Innovation Award from American Heart Association - Yahoo Finance

Bone Marrow Stem Cells Comments Off on Study of SanBio’s Stem Cell Treatment for Stroke Receives Innovation Award from American Heart Association – Yahoo Finance | February 27th, 2017

Aurangabad: After earning distinction in the field of cadaver organ donations at the state level, the city is now also emerging as a hub for tissue transplant after a city-based private hospital successfully performed Bone Marrow Transplant (BMT) on two patients.

"We performed the BMT on two people 25-year-old male and 55-year-old female a few weeks ago. With this, we have become the first and only centre in Marathwada to provide such treatment," Kamalnayan Bajaj Hospital CEO Shamim Khan said.

He described the treatment as complete care from diagnosis to cure at one point to any patient suffering from either genetic or acquired disorder of blood. There exist two forms of BMT namely Autologous BMT and Allogeneic BMT and the Kamalnayan Bajaj Hospital has performed the former procedure on two patients.

"Autologous BMT is where patient's own stem cells are used while for Allogenic BMT, the stem cells are from a matched donor. Both procedures can offer cure to deadly diseases like blood cancers, lymphoma, myeloma and genetic diseases such as thalassemia and sickle cell anemia, among others," said Venkatesh Ekbote, consultant Hematologist at the hospital.

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City hospital successfully performs bone marrow transplant - Times of India

Bone Marrow Stem Cells Comments Off on City hospital successfully performs bone marrow transplant – Times of India | February 23rd, 2017

February 22, 2017 12:53 PM

Bryan Altman

In 2016 Angels ace Garrett Richards took to the mound just six times before being shut down for the season on May 6, 2016 due to a partial tear of his UCL (ulnar collateral ligament) in his elbow, an injury that typically requires Tommy John surgery and a prolonged absence from any baseball activities.

Fortunately for Richards his tear was a unique one as it ran lengthwise along his UCL, as opposed to a standard tear which goes across ones ligament. This, combined with new advances in stem cell technology, gave Richards the option to avoid going under the knife and instead undergo stem cell treatment.

This and much more on the topic of stem cell research and its role in baseball was revealed in a recent piece published byYahoo.coms Jeff Passan, who also went into plenty of detail regarding the nature of the actual stem cell treatment.

From Yahoo.com

A doctor guided a needle into the iliac crest of his pelvic bone and began to extract bone marrow. Richards was wide awake, the blessing of local anesthesia saving him from physical pain but not the anxiety that crept into his head: Is this really going to work?

Within a few minutes, the harvested marrow was hurried to a centrifuge, spun to separate the good stuff, mixed into a slurry of platelet-rich plasma (PRP) and readied to inject into Richards damaged right elbow.

Science, bro, Richardsreportedly told Passan. Im a believer now.

Its hard not to be if youre Richards. According to the article, if Richards opted for Tommy John surgery the earliest possible return date for him would have been following the 2017 All-Star break.

Now, Richards is poised to start the season on the hill for the Angels and has been throwing 98 MPH fastballs once again in spring training.

I feel as good as I ever have throwing a baseball, said at the teams spring training facility on Monday.

For Richards, the results have seemingly turned out stellar, and while stem cell treatment could revolutionize baseball, there is still a little bit of skepticism regarding the procedure.

From Yahoo.com

In May 2013, a paper published in the American Journal of Sports Medicine found 30 of 34 overhand throwers with partial UCL tears who used PRP had returned to their previous level of competition. This was reason for celebration. If a player could avoid the 14-month-plus recovery from the surgery, better for him as well as the team.

Another study arrived in 2016 that didnt cast doubt on the value of orthobiologics so much as offer a different avenue: rest. The 28 players used everything from electrical stimulation, ultrasound, laser therapy, massage and other soft-tissue work. And when paired with rest, their return to previous level came in at 84 percent. It was almost exactly as effective as PRP.

Even though Richards is good to go,neither him or the Angels plan on taking any chances with his arm this year.

Passan notes that Richards has used his time off to reassess his mechanics and fix any inefficiencies in his delivery, which should also help him stay healthy.

Hell be targeting a pitch count below 100 for each game and is looking to keep his workload under 200 innings, which should hopefully keep the Angels ace on the mound and off the operating/stem cell treatment table for the foreseeable future.

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Garrett Richards Among Pitchers Using Stem Cell Treatment Over ... - CBS Local

Bone Marrow Stem Cells Comments Off on Garrett Richards Among Pitchers Using Stem Cell Treatment Over … – CBS Local | February 23rd, 2017

The search is still on to find a matching stem cell/bone marrow donor for five month old Madalayna Ducharme. The initial search of the Canadian OneMatch Stem Cell and Marrow Network as well as Bone Marrow Donors Worldwide (BMDW) have not yet identified a matching donor for Madalayna.

Madalayna was recently diagnosd with malignant infantile osteopetrosis, a genetic disorder that prevents her bones from working properly and they become too dense. This disorder attacks vision, hearing and is life threatening.

On Friday, February 24th there is another opportunity to help Madalayna find her match. The Katelyn Bedard Bone Marrow Association will host a Get Swabbed! registration event at Holy Names High School 1400 Northwood Street from 10am to 1:30pm.

The general public is invited to join the students and staff at Holy Names High School to keep the groundswell surging in an effort to ultimately find that life saving match for Madalayna.

The age requirement to register as a Stem Cell donor is 17 to 35 years. The registrant must possess a Canadian Government issued health card.

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Still Searching For A StemCell/Bone Marrow Donor For Baby Madalayna - windsoriteDOTca News

Bone Marrow Stem Cells Comments Off on Still Searching For A StemCell/Bone Marrow Donor For Baby Madalayna – windsoriteDOTca News | February 23rd, 2017

Cells within our bodies divide and change over time, with thousands of chemical reactions occurring within each cell daily. This makes it difficult for scientists to understand whats happening inside. Now, tiny nanostraws developed by Stanford researchers offer a method of sampling cell contents without disrupting its natural processes.

Nicholas Melosh, associate professor of materials science and engineering, developed a new, non-destructive system for sampling cells with nanoscale straws. The system could help uncover mysteries about how cells function. (Image credit: L.A. Cicero)

A problem with the current method of cell sampling, called lysing, is that it ruptures the cell. Once the cell is destroyed, it cant be sampled from again. This new sampling system relies on tiny tubes 600 times smaller than a strand of hair that allow researchers to sample a single cell at a time. The nanostraws penetrate a cells outer membrane, without damaging it, and draw out proteins and genetic material from the cells salty interior.

Its like a blood draw for the cell, said Nicholas Melosh, an associate professor of materials science and engineering and senior author on a paper describing the work published recently in Proceedings of the National Academy of Sciences.

The nanostraw sampling technique, according to Melosh, will significantly impact our understanding of cell development and could lead to much safer and effective medical therapies because the technique allows for long term, non-destructive monitoring.

What we hope to do, using this technology, is to watch as these cells change over time and be able to infer how different environmental conditions and chemical cocktails influence their development to help optimize the therapy process, Melosh said.

If researchers can fully understand how a cell works, then they can develop treatments that will address those processes directly. For example, in the case of stem cells, researchers are uncovering ways of growing entire, patient-specific organs. The trick is, scientists dont really know how stem cells develop.

For stem cells, we know that they can turn into many other cell types, but we do not know the evolution how do they go from stem cells to, say, cardiac cells? There is always a mystery. This sampling technique will give us a clearer idea of how its done, said Yuhong Cao, a graduate student and first author on the paper.

The sampling technique could also inform cancer treatments and answer questions about why some cancer cells are resistant to chemotherapy while others are not.

With chemotherapy, there are always cells that are resistant, said Cao. If we can follow the intercellular mechanism of the surviving cells, we can know, genetically, its response to the drug.

The sampling platform on which the nanostraws are grown is tiny about the size of a gumball. Its called the Nanostraw Extraction (NEX) sampling system, and it was designed to mimic biology itself.

In our bodies, cells are connected by a system of gates through which they send each other nutrients and molecules, like rooms in a house connected by doorways. These intercellular gates, called gap junctions, are what inspired Melosh six years ago, when he was trying to determine a non-destructive way of delivering substances, like DNA or medicines, inside cells. The new NEX sampling system is the reverse, observing whats happening within rather than delivering something new.

Its a super exciting time for nanotechnology, Melosh said. Were really getting to a scale where what we can make controllably is the same size as biological systems.

Building the NEX sampling system took years to perfect. Not only did Melosh and his team need to ensure cell sampling with this method was possible, they needed to see that the samples were actually a reliable measure of the cell content, and that samples, when taken over time, remained consistent.

When the team compared their cell samples from the NEX with cell samples taken by breaking the cells open, they found that 90 percent of the samples were congruous. Meloshs team also found that when they sampled from a group of cells day after day, certain molecules that should be present at constant levels remained the same, indicating that their sampling accurately reflected the cells interior.

With help from collaborators Sergiu P. Pasca, assistant professor of psychiatry and behavioral sciences, and Joseph Wu, professor of radiology, Melosh and co-workers tested the NEX sampling method not only with generic cell lines, but also with human heart tissue and brain cells grown from stem cells. In each case, the nanostraw sampling reflected the same cellular contents as lysing the cells.

The goal of developing this technology, according to Melosh, was to make an impact in medical biology by providing a platform that any lab could build. Only a few labs across the globe, so far, are employing nanostraws in cellular research, but Melosh expects that number to grow dramatically.

We want as many people to use this technology as possible, he said. Were trying to help advance science and technology to benefit mankind.

Melosh is also a professor in the photon science directorate at SLAC National Accelerator Laboratory, a member of Stanford Bio-X, the Child Health Research Institute, the Stanford Neurosciences Institute, Stanford ChEM-H and the Precourt Institute for Energy. Wu is also the Simon H. Stertzer, MD, Professor; he is director of the Stanford Cardiovascular Institute and a member of Stanford Bio-X, the Child Health Research Institute, Stanford ChEM-H and the Stanford Cancer Institute. Pasca is also a member of Stanford Bio-X, the Child Health Research Institute, the Stanford Neurosciences Institute and Stanford ChEM-H.

The work was funded by the National Institute of Standards and Technology, the Knut and Alice Wallenberg Foundation, the National Institutes of Health, Stanford Bio-X, the Progenitor Cell Biology Consortium, the National Institute of Mental Health, an MQ Fellow award, the Donald E. and Delia B. Baxter Foundation and the Child Health Research Institute.

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Stanford-developed nanostraws sample a cell's contents without damage - Stanford University News

Cardiac Stem Cells Comments Off on Stanford-developed nanostraws sample a cell’s contents without damage – Stanford University News | February 21st, 2017

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This colored scanning electron micrograph (SEM) is showing the internal structure of a broken finger bone. Here, the periosteum (outer bone membrane, pink), compact bone (yellow) and bone marrow (red), in the medullary cavity, can be seen. Photo Credit: STEVE GSCHMEISSNER/Science Photo Library/Getty Images

Updated July 15, 2016.

Bone marrow is the soft, flexible connective tissue within bone cavities. A component of the lymphatic system, bone marrow functions primarily to produce blood cells and to store fat. Bone marrow is highly vascular, meaning that it is richly supplied with a large number of blood vessels. There are two categories of bone marrow tissue: red marrow and yellow marrow. From birth to early adolescence, the majority of our bone marrow is red marrow.

As we grow and mature, increasing amounts of red marrow is replaced by yellow marrow. On average, bone marrow can generate hundreds of billions of new blood cells every day.

Bone marrow is separated into a vascular section and non-vascular sections. The vascular section contains blood vessels that supply the bone with nutrients and transport blood stem cells and mature blood cells away from the bone and into circulation. The non-vascular sections of the bone marrow are where hematopoiesis or blood cell formation occurs. This area contains immature blood cells, fat cells, white blood cells (macrophages and plasma cells), and thin, branching fibers of reticular connective tissue. While all blood cells are derived from bone marrow, some white blood cells mature in other organs such as the spleen, lymph nodes, and thymus gland.

The major function of bone marrow is to generate blood cells. Bone marrow contains two main types of stem cells. Hematopoietic stem cells, found in red marrow, are responsible for the production of blood cells.

Bone marrow mesenchymal stem cells (multipotent stromal cells) produce the non-blood cell components of marrow, including fat, cartilage, fibrous connective tissue (found in tendons and ligaments), stromal cells that support blood formation, and bone cells.

In adults, red marrow is confined mostly to skeletal system bones of the skull, pelvis, spine, ribs, sternum, shoulder blades, and near the point of attachment of the long bones of the arms and legs. Not only does red marrow produce blood cells, but it also helps to remove old cells from circulation. Other organs, such as the spleen and liver, also filter aged and damaged blood cells from the blood. Red marrow contains hematopoietic stem cells that produce two other types of stem cells: myeloid stem cells and lymphoid stem cells. These cells develop into red blood cells, white blood cells, or platelets. (See, bone marrow stem cells).

Yellow marrow consists primarily of fat cells. It has poor vascular supply and is composed of hematopoietic tissue that has become inactive. Yellow marrow is found in spongy bones and in the shaft of long bones. When blood supply is extremely low, yellow marrow can be converted to red marrow in order to produce more blood cells.

If bone marrow becomes damaged or diseased, it can result in low blood cell production. Bone marrow disease can develop from bone marrow and blood cancers such as leukemia. Radiation exposure, certain kind of infections, and diseases such as aplastic anemia and myelofibrosis can also cause blood and marrow disorders. These diseases compromise the immune system and deprive organs and tissues of the life giving oxygen and nutrients they need. A bone marrow transplant may be done in order to treat blood and marrow diseases. In the process, damaged blood stem cells are replaced by healthy cells obtained form a donor. The healthy stem cells can be obtained from the donor's blood or bone marrow. Bone marrow is extracted from bones such as the hip or sternum. Stem cells may also be obtained from umbilical cord blood to be used for transplantation.

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Bone Marrow - Structure, Function, Disease and More

Bone Marrow Stem Cells Comments Off on Bone Marrow – Structure, Function, Disease and More | February 21st, 2017

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Jonathan Pitre battles blood, lung infections before second stem cell transplant Ottawa Citizen People with RDEB have a fault in the gene responsible for a specific kind of collagen that connects the outer layer of skin, the epidermis, with those below it. The clinical trial seeks a biochemical correction to that fault. If the transplant works ...

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Jonathan Pitre battles blood, lung infections before second stem cell transplant - Ottawa Citizen

Skin Stem Cells Comments Off on Jonathan Pitre battles blood, lung infections before second stem cell transplant – Ottawa Citizen | February 21st, 2017

The disease is caused by the immune system malfunctioning and mistakenly attacking nerve cells in the brain and spinal cord.

It leads to problems with movement, vision, balance and speech.

The treatment, autologous hematopoietic stem cell transplantation (AHSCT), was given to patients with advanced forms of the disease who had failed to respond to other medications.

A similar approach has been trialed on people with certain forms of cancer, with encouraging early results.

Dr Paolo Muraro, the new study's lead author, said: "We previously knew this treatment reboots or resets the immune system but we didn't know how long the benefits lasted.

"In this study, which is the largest long-term follow-up study of this procedure, we've shown we can 'freeze' a patient's disease - and stop it from becoming worse, for up to five years."

The researchers noted, however, that the nature of the treatment, which involves aggressive chemotherapy, carried significant risks.

The chemotherapy deactivates the immune system for a short period of time, which can lead to greater risk of infection - of the 281 patients who received AHSCT, eight died in the 100 days after treatment.

The treatment works by destroying the immune cells responsible for attacking the nervous system.

Patients were given a drug which encourages stem cells to move from the bone marrow into the bloodstream, where they were removed from the body.

High-dose chemotherapy was then administered to kill all immune cells, before the patient's own stem cells were put back into the body to "reset" the immune system.

Nearly three in four (73%) patients with relapsing MS - where the disease flares up before symptoms improve - found their symptoms did not worsen for five years after having AHSCT, compared with one in three patients with progressive MS, the more severe variant of the disease.

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New stem cell treatment 'freezes' multiple sclerosis - Telegraph.co.uk

Bone Marrow Stem Cells Comments Off on New stem cell treatment ‘freezes’ multiple sclerosis – Telegraph.co.uk | February 20th, 2017

Researchers in Germany have discovered that a tumor suppressor protein thought to prevent acute myeloid leukemia (AML) can actually promote a particularly deadly form of the disease. The study, "RUNX1 cooperates with FLT3-ITD to induce leukemia," which will be published online February 17 in The Journal of Experimental Medicine, suggests that targeting this protein could be an effective treatment for certain AML patients.

AML accounts for over 1 percent of all cancer deaths in the United States and is characterized by an excessive proliferation of hematopoietic stem cells in the bone marrow and their subsequent failure to differentiate into white blood cells. AML can be caused by various combinations of gene mutations. One of the most common mutations is in the gene encoding the cell surface signaling protein FLT3, and patients with this mutation show poor rates of survival. The mutant form of FLT3 can promote cell proliferation, but experiments in mice have shown that it isn't sufficient to block white blood cell differentiation and induce AML on its own.

Carol Stocking and colleagues at the Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology in Hamburg noticed that many patients carrying the mutant form of FLT3 also showed increased levels of a transcription factor called RUNX1. "This was unexpected because up to 20 percent of AML patients carry mutations that inactivate RUNX1, which is generally considered to be a tumor suppressor that prevents the formation of leukemias," Stocking says.

Stocking's team found that reducing RUNX1 levels attenuated the ability of human AML cells expressing mutant FLT3 to form tumors when injected into mice. In contrast, elevated RUNX1 levels worked with mutant FLT3 to induce AML. Mouse hematopoietic stem cells expressing mutant FLT3 were highly proliferative, and co-expression of RUNX1 blocked their differentiation, allowing them to give rise to AML.

Mutant FLT3 appears to stabilize and activate RUNX1 by promoting the transcription factor's phosphorylation. Active RUNX1 then blocks white blood cell differentiation, at least in part, by inducing another transcription factor called Hhex. Hematopoietic stem cells expressing both Hhex and mutant FLT3 also gave rise to AML, the researchers found.

RUNX1 may therefore suppress the initiation of AML but, after being activated by mutant FLT3, block white blood cell differentiation and promote tumor development. "Therapies that can reverse this differentiation block may offer significant therapeutic efficacy in AML patients with FLT3 mutations," says Stocking. "Ablating RUNX1 is toxic to leukemic cells but not to normal hematopoietic stem cells, so inhibiting RUNX1 may be a promising target in combination with FLT3 inhibitors."

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Tumor suppressor promotes some acute myeloid leukemias, study reveals - Science Daily

Bone Marrow Stem Cells Comments Off on Tumor suppressor promotes some acute myeloid leukemias, study reveals – Science Daily | February 19th, 2017

February 14, 2017 Salk scientists create synthetic brain systems called 'circuitoids' to better understand dysfunctional movements in Parkinson's, ALS and other diseases. Confocal microscope immunofluorescent image of a spinal cord neural circuit made entirely from stem cells and termed a 'circuitoid.' Credit: Salk Institute

Not everyone is Fred Astaire or Michael Jackson, but even those of us who seem to have two left feet have got rhythmin our brains. From breathing to walking to chewing, our days are filled with repetitive actions that depend on the rhythmic firing of neurons. Yet the neural circuitry underpinning such seemingly ordinary behaviors is not fully understood, even though better insights could lead to new therapies for disorders such as Parkinson's disease, ALS and autism.

Recently, neuroscientists at the Salk Institute used stem cells to generate diverse networks of self-contained spinal cord systems in a dish, dubbed circuitoids, to study this rhythmic pattern in neurons. The work, which appears online in the February 14, 2017, issue of eLife, reveals that some of the circuitoidswith no external promptingexhibited spontaneous, coordinated rhythmic activity of the kind known to drive repetitive movements.

"It's still very difficult to contemplate how large groups of neurons with literally billions if not trillions of connections take information and process it," says the work's senior author, Salk Professor Samuel Pfaff, who is also a Howard Hughes Medical Institute investigator and holds the Benjamin H. Lewis Chair. "But we think that developing this kind of simple circuitry in a dish will allow us to extract some of the principles of how real brain circuits operate. With that basic information maybe we can begin to understand how things go awry in disease."

Nerve cells in your brain and spinal cord connect to one another much like electronic circuits. And just as electronic circuits consist of many components, the nervous system contains a dizzying array of neurons, often resulting in networks with many hundreds of thousands of cells. To model these complex neural circuits, the Pfaff lab prompted embryonic stem cells from mice to grow into clusters of spinal cord neurons, which they named circuitoids. Each circuitoid typically contained 50,000 cells in clumps just large enough to see with the naked eye, and with different ratios of neuronal subtypes.

With molecular tools, the researchers tagged four key subtypes of both excitatory (promoting an electrical signal) and inhibitory (stopping an electrical signal) neurons vital to movement, called V1, V2a, V3 and motor neurons. Observing the cells in the circuitoids in real time using high-tech microscopy, the team discovered that circuitoids composed only of V2a or V3 excitatory neurons or excitatory motor neurons (which control muscles) spontaneously fired rhythmically, but that circuitoids comprising only inhibitory neurons did not. Interestingly, adding inhibitory neurons to V3 excitatory circuitoids sped up the firing rate, while adding them to motor circuitoids caused the neurons to form sub-networks, smaller independent circuits of neural activity within a circuitoid.

"These results suggest that varying the ratios of excitatory to inhibitory neurons within networks may be a way that real brains create complex but flexible circuits to govern rhythmic activity," says Pfaff. "Circuitoids can reveal the foundation for complex neural controls that lead to much more elaborate types of behaviors as we move through our world in a seamless kind of way."

Because these circuitoids contain neurons that are actively functioning as an interconnected network to produce patterned firing, Pfaff believes that they will more closely model a normal aspect of the brain than other kinds of cell culture systems. Aside from more accurately studying disease processes that affect circuitry, the new technique also suggests a mechanism by which dysfunctional brain activity could be treated by altering the ratios of cell types in circuits.

Explore further: Scientists discover new mechanism of how brain networks form

More information: Matthew J Sternfeld et al, Speed and segmentation control mechanisms characterized in rhythmically-active circuits created from spinal neurons produced from genetically-tagged embryonic stem cells, eLife (2017). DOI: 10.7554/eLife.21540

Journal reference: eLife

Provided by: Salk Institute

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Your brain's got rhythm - Medical Xpress

Spinal Cord Stem Cells Comments Off on Your brain’s got rhythm – Medical Xpress | February 15th, 2017

OCASCR scientist Lin Liu at work. Photo provided.

Working together, scientists from Oklahoma State University, the University of Oklahoma Health Sciences Center and the Oklahoma Medical Research Foundation are advancing adult stem cell research to treat some of todays most devastating diseases.

Under the umbrella of the Oklahoma Center for Adult Stem Cell Research (OCASCR), created with funding from the Oklahoma Tobacco Settlement Endowment Trust, these scientists have amassed groundbreaking findings in one of the fastest growing areas of medical research.

We have made exciting progress, said OCASCR scientist Lin Liu, director of the Oklahoma Center for Respiratory and Infectious Diseases and director of the Interdisciplinary Program in Regenerative Medicine at Oklahoma State University.

We can convert adult stem cells into lung cells using our engineering process in petri dishes, which offers the possibility to repair damaged lung tissues in lung diseases, said Liu, whose research primarily focuses on lung and respiratory biology and diseases.

Using our engineered cells, we can also reverse some pathological features. These studies give us hope for an eventual application of these cells in humans.

Adult stem cells in the body are capable of renewing themselves and becoming various types of cells.

Until recently, stem cell treatments were largely restricted to blood diseases. However, new studies suggest many other types of adult stem cells can be used for medical treatment, and the Oklahoma Center for Adult Stem Cell Research was created to promote this branch of research.

OCASCR scientist Lin Liu and his team discussing their work. Photo provided.

Liu said the discipline provides hope for many ailments.

What most fascinated me in stem cell research is the hope that we may be able to use stem cells from our own body; for example, bone marrow or fat tissues to cure lung diseases, Liu said.

It is impossible to know exactly which diseases will respond to treatments.However, results of early experiments suggest many diseases should benefit from this type of research, including lung, heart, Alzheimers and Parkinsons diseases, as well as cancer, diabetes and spinal cord injuries. The field is often referred to as regenerative medicine, because of the potential to create good cells in place of bad ones.

While the application of stem cells can be broad, Liu hopes that his TSET-funded work will help develop treatments for diseases caused by tobacco use.

The goal of my research team is to find cures for lung diseases, Liu said. One such disease is chronic obstructive pulmonary disease (COPD).

COPD is the third leading cause of death in the country and cigarette smoking is the leading cause of COPD.

Cigarette smoking is also a risk factor for another fatal lung disease, idiopathic pulmonary fibrosis (IPF), which has a mean life expectancy of 3 to 5 years after diagnosis, he added.

There is no cure for COPD or IPF. The current treatments of COPD and IPF only reduce symptoms or slow the disease progression.

Using OCASCR/TSET funding, my team is researching the possibility to engineer adult stem cells using small RNA molecules existing in the body to cure COPD, IPF and other lung diseases such as pneumonia caused by flu, Liu said.

This is vital research, considering that more than11 million peoplehave been diagnosed with COPD, but millions more may have the disease without even knowing it, according to the American Lung Association.

Despite declining smoking rates and increased smokefree environments, tobacco use continues to cause widespread health challenges and scientists will continue working to develop treatments to deal with the consequences of smoking.

We need to educate the public more regarding the harms of cigarette smoking, Liu said. My research may offer future medicines for lung diseases caused by cigarette smoking.

Under the umbrella of the Oklahoma Center for Adult Stem Cell Research (OCASCR), created with funding from the Oklahoma Tobacco Settlement Endowment Trust, these scientists have amassed groundbreaking findings in one of the fastest growing areas of medical research. Photo provided.

Liu has been conducting research in the field of lung biology and diseases for more than two decades.

However, his interests in adult stem cell therapy began in 2010 when OCASCR was established through a grant with TSET, which provided funding to Oklahoma researchers for stem cell research.

I probably would have never gotten my feet into stem cell research without OCASCR funding support, he said. OCASCR funding also facilitated the establishment of the Interdisciplinary Program in Regenerative Medicine at OSU.

These days, Liu finds himself fully immersed in the exciting world of adult stem cell research and collaborating with some of Oklahomas best scientific minds.

Dr. Liu and his colleagues are really thriving. It was clear seven years ago that regenerative medicine was a hot topic and we already had excellent scientists in the Oklahoma, said Dr. Paul Kincade, founding scientific director of OCASCR. All they needed was some resources to re-direct and support their efforts. OSU investigators are using instruments and research grants supplied by OCASCR to compete with groups worldwide. TSET can point to their achievements with pride.

The Oklahoma Center for Adult Stem Cell Research represents collaboration between scientists all across the state, aiming to promote studies by Oklahoma scientists who are working with stem cells present in adult tissues.

The center opened in 2010 and has enhanced adult stem cell research by providing grant funding for researchers, encouraging recruitment of scientists and providing education to the people of Oklahoma.

We are fortunate that the collaboration at the Oklahoma Center for Adult Stem Cell Research is yielding such positive results, said John Woods, TSET executive director. This research is leading to ground breaking discoveries and attracting new researchers to the field. TSET is proud to fund that investments for Oklahomans.

Funding research is a major focus for TSET and it comes with benefits reaching beyond the lab. For every $1 TSET has invested at OCASCR, scientists have been able to attract an additional $4 for research at Oklahoma institutions, TSET officials said.

TSET also supports medical research conducted by the Stephenson Cancer Center and the Oklahoma Tobacco Research Center.

For more information, visit http://www.ocascr.org.

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OCASCR scientists make progress in TSET-funded adult stem cell research - NewsOK.com

Bone Marrow Stem Cells Comments Off on OCASCR scientists make progress in TSET-funded adult stem cell research – NewsOK.com | February 11th, 2017

OCASCR scientist Lin Liu at work. Photo provided.

Working together, scientists from Oklahoma State University, the University of Oklahoma Health Sciences Center and the Oklahoma Medical Research Foundation are advancing adult stem cell research to treat some of todays most devastating diseases.

Under the umbrella of the Oklahoma Center for Adult Stem Cell Research (OCASCR), created with funding from the Oklahoma Tobacco Settlement Endowment Trust, these scientists have amassed groundbreaking findings in one of the fastest growing areas of medical research.

We have made exciting progress, said OCASCR scientist Lin Liu, director of the Oklahoma Center for Respiratory and Infectious Diseases and director of the Interdisciplinary Program in Regenerative Medicine at Oklahoma State University.

We can convert adult stem cells into lung cells using our engineering process in petri dishes, which offers the possibility to repair damaged lung tissues in lung diseases, said Liu, whose research primarily focuses on lung and respiratory biology and diseases.

Using our engineered cells, we can also reverse some pathological features. These studies give us hope for an eventual application of these cells in humans.

Adult stem cells in the body are capable of renewing themselves and becoming various types of cells.

Until recently, stem cell treatments were largely restricted to blood diseases. However, new studies suggest many other types of adult stem cells can be used for medical treatment, and the Oklahoma Center for Adult Stem Cell Research was created to promote this branch of research.

OCASCR scientist Lin Liu and his team discussing their work. Photo provided.

Liu said the discipline provides hope for many ailments.

What most fascinated me in stem cell research is the hope that we may be able to use stem cells from our own body; for example, bone marrow or fat tissues to cure lung diseases, Liu said.

It is impossible to know exactly which diseases will respond to treatments.However, results of early experiments suggest many diseases should benefit from this type of research, including lung, heart, Alzheimers and Parkinsons diseases, as well as cancer, diabetes and spinal cord injuries. The field is often referred to as regenerative medicine, because of the potential to create good cells in place of bad ones.

While the application of stem cells can be broad, Liu hopes that his TSET-funded work will help develop treatments for diseases caused by tobacco use.

The goal of my research team is to find cures for lung diseases, Liu said. One such disease is chronic obstructive pulmonary disease (COPD).

COPD is the third leading cause of death in the country and cigarette smoking is the leading cause of COPD.

Cigarette smoking is also a risk factor for another fatal lung disease, idiopathic pulmonary fibrosis (IPF), which has a mean life expectancy of 3 to 5 years after diagnosis, he added.

There is no cure for COPD or IPF. The current treatments of COPD and IPF only reduce symptoms or slow the disease progression.

Using OCASCR/TSET funding, my team is researching the possibility to engineer adult stem cells using small RNA molecules existing in the body to cure COPD, IPF and other lung diseases such as pneumonia caused by flu, Liu said.

This is vital research, considering that more than11 million peoplehave been diagnosed with COPD, but millions more may have the disease without even knowing it, according to the American Lung Association.

Despite declining smoking rates and increased smokefree environments, tobacco use continues to cause widespread health challenges and scientists will continue working to develop treatments to deal with the consequences of smoking.

We need to educate the public more regarding the harms of cigarette smoking, Liu said. My research may offer future medicines for lung diseases caused by cigarette smoking.

Under the umbrella of the Oklahoma Center for Adult Stem Cell Research (OCASCR), created with funding from the Oklahoma Tobacco Settlement Endowment Trust, these scientists have amassed groundbreaking findings in one of the fastest growing areas of medical research. Photo provided.

Liu has been conducting research in the field of lung biology and diseases for more than two decades.

However, his interests in adult stem cell therapy began in 2010 when OCASCR was established through a grant with TSET, which provided funding to Oklahoma researchers for stem cell research.

I probably would have never gotten my feet into stem cell research without OCASCR funding support, he said. OCASCR funding also facilitated the establishment of the Interdisciplinary Program in Regenerative Medicine at OSU.

These days, Liu finds himself fully immersed in the exciting world of adult stem cell research and collaborating with some of Oklahomas best scientific minds.

Dr. Liu and his colleagues are really thriving. It was clear seven years ago that regenerative medicine was a hot topic and we already had excellent scientists in the Oklahoma, said Dr. Paul Kincade, founding scientific director of OCASCR. All they needed was some resources to re-direct and support their efforts. OSU investigators are using instruments and research grants supplied by OCASCR to compete with groups worldwide. TSET can point to their achievements with pride.

The Oklahoma Center for Adult Stem Cell Research represents collaboration between scientists all across the state, aiming to promote studies by Oklahoma scientists who are working with stem cells present in adult tissues.

The center opened in 2010 and has enhanced adult stem cell research by providing grant funding for researchers, encouraging recruitment of scientists and providing education to the people of Oklahoma.

We are fortunate that the collaboration at the Oklahoma Center for Adult Stem Cell Research is yielding such positive results, said John Woods, TSET executive director. This research is leading to ground breaking discoveries and attracting new researchers to the field. TSET is proud to fund that investments for Oklahomans.

Funding research is a major focus for TSET and it comes with benefits reaching beyond the lab. For every $1 TSET has invested at OCASCR, scientists have been able to attract an additional $4 for research at Oklahoma institutions, TSET officials said.

TSET also supports medical research conducted by the Stephenson Cancer Center and the Oklahoma Tobacco Research Center.

For more information, visit http://www.ocascr.org.

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OCASCR scientists make progress in TSET-funded adult stem cell ... - NewsOK.com

Bone Marrow Stem Cells Comments Off on OCASCR scientists make progress in TSET-funded adult stem cell … – NewsOK.com | February 11th, 2017

Science Daily

Scientists discover an unexpected influence on dividing stem cells ... Science Daily When it divides, a stem cell has a choice: produce more stem cells or turn into the specific types of cells that compose skin, muscle, brain, or other tissue. and more »

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Scientists discover an unexpected influence on dividing stem cells ... - Science Daily

Skin Stem Cells Comments Off on Scientists discover an unexpected influence on dividing stem cells … – Science Daily | February 11th, 2017

Greg Iger/Keck Medicine of USC

Kristopher Boesen, who broke his neck in a car accident, regained the ability to move his arms and hands after his spinal cord was injected with stem cells.

Two years after having a stroke at 31, Sonia Olea Coontz remained partially paralysed on her right side. She could barely move her arm, had slurred speech and needed a wheelchair to get around. In 2013, Coontz enrolled in a small clinical trial. The day after a doctor injected stem cells around the site of her stroke, she was able to lift her arm up over her head and speak clearly. Now she no longer uses a wheelchair and, at 36, is pregnant with her first child.

Coontz is one of stem-cell therapy's miracle patients, says Gary Steinberg, chair of neurosurgery at Stanford School of Medicine in California, and Coontz's doctor. Conventional wisdom said that her response was impossible: the neural circuits damaged by the stroke were dead. Most neuroscientists believed that the window for functional recovery extends to only six months after the injury.

Stem-cell therapies have shown great promise in the repair of brain and spinal injuries in animals. But animal models often behave differently from humans nervous-system injuries in rats, for example, heal more readily than they do in people. Clinical trial results have been mixed. Interesting signals from small trials have faded away in larger ones. There are plenty of unknowns: which stem cells are the right ones to use, what the cells are doing when they work and how soon after an injury they can be used.

The field is still young. Stem cells are poorly understood, and so is what happens after a spinal-cord injury or stroke. Yet, there are success stories, such as Coontz's, which seem to show that therapy using the right sort of stem cell can lead to functional improvements when tried in the right patients and at the right time following an injury. Researchers are fired up to determine whether stem-cell therapies can help people who are paralysed to regain some speech and motor control and if so, what exactly is going on.

Neurologists seeking functional restoration are up against the limited ability of the human central nervous system to heal. The biology of the brain and spinal cord seems to work against neuroregeneration, possibly because overgrowth of nerves could lead to faulty connections in the finely patterned architecture of the brain and spine, says Mark Tuszynski, a neurologist at the University of California, San Diego. Local chemical signals in the central nervous system tamp down growth. Over time, scarring develops, which prevents the injury from spreading, but also keeps cells from entering the site.

It's really hard to fix the biology, says Charles Yu Liu, a neurosurgeon and director of the University of Southern California Neurorestoration Center in Los Angeles. Stem cells seem to promise a workaround.

So far, neural regeneration cell therapy has had only anecdotal success, leaving investors and patients disappointed. In people with Parkinson's disease, for example, neurosurgeons replaced dead and dying dopamine-producing neurons with fetal neurons. Although initial results were promising, in larger studies, patients reported involuntary movements. Another effort tried treating people who'd had a stroke with cells derived from tumours; the results were mixed, and researchers were uneasy about the cells' cancerous source.

In recent years, researchers have had success with stem cells coaxed to develop into particular cell types, such as neural support cells. Tuszynski has showed how well stem cells can work at least, in animal models1. His group implanted neural stem cells derived from human fetal tissue into rats with severe spinal-cord injuries. Seven weeks later, the cells had bridged the gap where the spinal cord had been cut and the animals were able to walk again. The cells used in the study were manufactured by Neuralstem of Rockville, Maryland. The group has shown that other kinds of stem cell, including those derived from adult tissue, also work. Tuszynski has seen similar results in a rat spinal-cord-injury model, using neural stem cells made from the tissues of a healthy 86-year-old volunteer2.

Mark Tuszynski/Ken Kadoya/Ref. 3

Regeneration of axons (red) beyond implanted neural progenitor cells (green) in a rat with a spinal injury.

But animal studies are also making it clear that simply regrowing the connective wiring of the nervous system to bridge damaged areas is not enough, says Zhigang He, who studies neural repair at the Harvard Stem Cell Institute in Cambridge, Massachusetts. No matter what the animal model is, he says, the axons don't always grow into the right places. It's not enough to have a nerve, that nerve must become part of a functional circuit.

There is growing evidence that besides becoming replacement nerves, stem cells perform other functions they also seem to generate a supportive milieu that may encourage the natural recovery process or prevent further damage after an injury. Many types of neural stem cell secrete a mix of molecules that unlock suppressed growth pathways in nerves. Earlier this year, Tuszynski reported that any sort of spinal-cord stem cell, whether derived from adult tissues or embryos, from humans, rats or mice, could trigger native neural regeneration in rats3. But his success in rats has not yet translated into clinical trials. More work is needed, Tuszynski says, to determine which type of cell will work best for which particular injury.

For people who have had a stroke or spinal-cord injury, physical therapy is currently the best hope for recovery in the weeks and months after the injury. The brain is plastic and can co-opt other circuits and pathways to compensate for damage and to restore function. Once the inflammation ebbs and the brain adjusts, people can start to regain function. But the window of opportunity is short. Most people don't make functional gains after six months.

That timeline is why the remarkable recovery enjoyed by Coontz and other patients with chronic stroke in the same clinical trial is so surprising, says Steinberg. This changes our whole notion of recovery, he says. There were 18 people in the trial Coontz took part in, and all were treated using stem cells manufactured by SanBio of Mountain View, California. The company's cells are bone-marrow-derived mesenchymal stem cells. The cells are treated with a DNA fragment that is transiently expressed in them, and causes changes in their protein-expression patterns. In animal studies, these cells promote the migration and growth of native neural stem cells, among other effects.

The trial, which was designed to look at safety as well as efficacy, recruited patients after an ischaemic stroke. During this kind of stroke, a clot cuts off the blood supply to part of the brain, causing significant damage. Patients in the trial had all had ischaemic strokes deep in the brain 736 months earlier past the 6-month window for significant recovery. Each patient was injected with either 2.5 million, 5 million or 10 million of SanBio's cells4. Steinberg has followed participants for 24 months; an interim study at 12 months reported that most patients showed functional improvements. Some, like Coontz, achieved almost complete recovery.

What is not clear, however, is what the stem-cell injections do in the brain. In animal studies, the SanBio cells do not turn into neurons, but seem to send supporting signals to native cells in the brain. Indeed, preclinical research shows that the cells do not integrate into the brain most die after 12 months. Instead, the cells seem to secrete growth factors that encourage the formation of new neurons and blood vessels, and foster connections called synapses between neurons. And in rats, the nerve-cell connections that extended from one side of the brain to the other, as well as into the spinal cord, lasted, even though the injected cells did not4.

But these mechanisms are not sufficient to explain Coontz's overnight restoration of function, says Steinberg. He is entertaining several hypotheses, including that the needle used to deliver the cells may have had some effect. One week after treatment, we saw abnormalities in the premotor cortex that went away after one month, he says. The size of these microlesions was strongly correlated with recovery at 12 months. A similar effect can happen when electrodes are implanted in the brains of people with Parkinson's, although this deep-brain stimulation quietens tremors for only a short time. The people who'd had a stroke had a lasting recovery, suggesting that both the needle and the stem cells may have played a part.

The SanBio trial was small, and did not have a placebo control; the company is now recruiting for a larger phase II trial. Of the 156 participants that will be recruited, two-thirds will have cells injected the others will have a sham surgery. Even the trial surgeons, including Steinberg, will not know who is getting which treatment. The main outcome measure will be whether patients' motor-skill scores improve on a test called the Fugl-Meyer Motor scale six months after treatment. Participants will be monitored for at least 12 months, and will also be evaluated with tests that look for changes in gait and dexterity. Meanwhile, Steinberg plans to study microlesions in animal models of stroke to determine whether they do have a role in recovery.

An ongoing clinical trial evaluating escalating doses of neural stem cells in patients with acute spinal-cord injuries is also looking promising. Asterias Biotherapeutics of Fremont, California, coaxes the cells to develop into progenitors of oligodendrocytes, a type of support cell that's found in the brain and spinal cord and that creates a protective insulation for neuronal axons.

The trial tests the safety and efficacy of administering these cells to people with recent cervical, or neck-level, spinal-cord injury. Interim results for patients who had received the two lower doses were presented at the International Spinal Cord Society meeting in September. After 90 days, 4 patients who received 10 million cells showed improved motor function; a fifth patient had not reached the 90-day mark yet. At one year, the three patients receiving a lower dose of two million cells showed measurable improvement in motor skills.

These cells were initially developed by Geron, a biotechnology company that has since moved away from regenerative medicine. Before spinning out Asterias in 2013, Geron had run a safety trial of the cells in people with a chronic lower-back injury. No issues were identified, and the US Food and Drug Administration agreed to let the company test the cells in patients who'd been recently injured. Asterias focused the current trial on patients with cervical injuries because these are closer to the brain, so new nerve cells have a shorter distance to grow to gain functional improvements. People with severe cervical spine injuries are typically paralysed below the level of the damage. The company's hope is to restore arm and hand function for people with such injuries, potentially making a tremendous difference to a person's independence and quality of life.

Asterias seems to have realized this hope in at least one patient who received one of the higher doses. Kristopher Boesen, who is 21, has had a dramatic recovery. In March, Boesen's car fishtailed in a rainstorm; he hit a telephone pole and broke his neck. About a month later, Boesen was still paralysed below the injury, and his neurological improvements seemed to have plateaued. His doctors at a trauma centre in Bakersfield, California, were in touch with Liu, who is an investigator in the Asterias trial. As soon as he was stable, Boesen travelled to Los Angeles to join the trial.

Liu injected Boesen's spinal cord with Asterias's cells in April. Two days later, Boesen started to move his hands, and in the summer, he regained the ability to move the toes on one foot.

Asterias Biotherapeutics

A surgeon prepares to inject stem cells to treat a spinal injury as part of Asterias's clinical trial.

Liu is excited about Boesen's response. He was looking at being quadriplegic, and now he's able to write, lift some weights with his hands, and use his phone, says Liu. For somebody to improve like this is highly unusual I want to be jumping out of my shoes. But Liu cautions that this is still a small trial, and that Boesen's response is just one anecdotal report. Until the results are borne out in a large, placebo-controlled clinical trial, Liu will remain earthbound.

The trial is currently recruiting between 5 and 8 patients for another cohort that will receive a doubled dose of 20 million cells. As the trial goes on, Asterias hopes to find clues about the underlying mechanism. We're looking at changes in the anatomy of the injury, says the company's chief scientific officer, Jane Lebkowski. She says that there is some evidence that axons have traversed the injury site in patients who have recovered function. Preclinical work suggests that the cells might be sending growth-encouraging chemical signals to the native tissue. And, as support cells, the astrocytes may also be preventing more neurons from dying in the aftermath of the acute spinal injury.

Not all clinical trials have performed so well. The SanBio and Asterias results are positive signals in a sea of negative or mixed trials. For example, StemCells of Newark, California, terminated its phase II trial of stem cells for the treatment of spinal-cord injury in May, and shortly afterwards announced that it will restructure its business. The company declined to comment for this article.

Physicians such as Liu and Steinberg temper their public enthusiasm about stem-cell therapies, so as not to give false hope to desperate patients. People with paralysing injuries or those who have a neurodegenerative disease are easy marks for unscrupulous stem-cell clinics, whose therapies are not only unproven, but also come with risks.

Patients say, 'Go ahead, doc, you can't make me any worse,' says Keith Tansey, a neurologist and researcher at the Methodist Rehabilitation Center in Jackson, Mississippi, and president-elect of the American Spinal Injury Association. Unfortunately, that is not the case. Cell therapies given at a clinic, outside the context of a clinical trial, can lead to chronic pain, take away what little function a patient has left and render a patient ineligible for future studies, says Tansey. He has seen the consequences in his clinical practice. I treated a kid who had two different tumours in his spinal cord from two different individuals' cells, he says.

Many unanswered questions remain about whether stem cells can heal the central nervous system in people, and how they might do it. Researchers also don't know what cells are the best to use. Is it enough for them to grow into supportive cells that send friendly growth signals, or is it better that they grow into replacement neurons? The answer is likely to differ depending on the site and nature of the disease or injury. If the stem cells are producing supportive factors that encourage growth and repair, it might be possible, says He, to discern what these are and give them directly to patients. But biologists are not yet close to deciphering the recipe for such a cocktail.

Every time we get an experiment done we realize it's more complex than we thought it would be.

Tansey agrees that there are many unknowns and these seem to be multiplying. Every time we get an experiment done we realize it's more complex than we thought it would be, he says. Tansey thinks that the best way to resolve such uncertainties is with carefully regulated clinical trials. Rat models will only tell us so much the human nervous system is much larger and is wired differently. If stem cells help patients such as Coontz and Boesen to regain their speech and give them greater independence without adverse effects, then it makes sense to continue, he says, even without knowing all the details of how they work.

Until these positive, but small, results are replicated in larger, controlled clinical trials, neurologists are containing their optimism. I'd like to hear of any clinical trial that has more than an anecdotal benefit, says Tansey. And Liu is anticipating the day when he won't need to control his elation. In a few years, perhaps there will be a genuine opportunity to jump for joy.

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Neuroscience: New nerves for old - Nature.com

Spinal Cord Stem Cells Comments Off on Neuroscience: New nerves for old – Nature.com | February 8th, 2017

ANDREW and Judy Kim are still searching the globe for a donor for their two-year-old son after he was diagnosed with a rare genetic condition.

The couple's son Alastair was diagnosed with chronic granulomatous disorder (CGD) in February last year.

Mr and Mrs Kim launched an appeal for help in September but the search is still on for a matching donor and their son still needs hospital treatment.

The life-threatening condition wipes out his immune system, meaning even the most minor infections leave him seriously ill.

A course of genetic therapy treatment to help him fight infections has been launched and Alastair has been treated at Oxford Children's Hospital and Great Ormond Street Hospital in London.

The only hope of a permanent cure lies in a bone marrow stem cell donor but it needs to be a 90 per cent genetic match and the family is calling for more East Asians to sign up as donors.

Mr Kim, 37, a medical research engineer, said: "It is not easy to find a match and we pray every day that it will work out.

"We have to make sure that Alastair does not get a cut because it could get infected and he does not have the ability to fight off bacteria.

"That could cascade down the line to something very dangerous for him.

"If we get ill then we have to stay away from him he loves our dog Choco Pie but he is not allowed to stroke her.

"We are doing our best to stay positive and raise awareness about his condition."

Mr and Mrs Kim, who live near Longworth with their other son Micah, five, have already searched the international register of more than four million donors but without success.

They are both of Korean descent so a matching donor will most likely be of Korean, Japanese or Chinese heritage.

The number of East Asians on international donor registers is very limited of the 617,000 registered donors in the UK just 0.5 per cent are east Asian.

The couple, who moved to Oxfordshire from Chicago nine years ago, are now appealing for people around the world, particularly East Asians, to order a free kit through a website they have set up, and take a two-minute home test to see if they could help.

Alastair has had numerous infections since he was born in September 2014.

He spent the first year-and-a-half of his life in and out of hospital but CGD is so rare, doctors never thought to test him for it but eventually a doctor at the John Radcliffe Hospital in Oxford decided to test Alastair for the condition.

The couple desperately want to find a matching donor, but also want to increase the number of East Asians on the donor register.

The couple have run several blood drives at Mrs Kim's office at Oxford University and at Harwell Oxford.

More than 90 people came forward and of those, five were able to donate blood that helped Alastair to fight infections.

Mr Kim added: "At a couple of blood drives we have found matches for other people and hopefully one day a match will found for Alastair."

To join the register go to allysfight.com

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The Scientist

Regulators OK Clinical Trials Using Donor Stem Cells The Scientist WIKIPEDIA, TMHLEEResearchers in Japan who have been developing a cell therapy for macular degeneration received support from health authorities this week (February 1) to begin a clinical trial using donor-derived induced pluripotent stem (IPS) cells ...

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Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to an embryonic stem celllike state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells. Although these cells meet the defining criteria for pluripotent stem cells, it is not known if iPSCs and embryonic stem cells differ in clinically significant ways. Mouse iPSCs were first reported in 2006, and human iPSCs were first reported in late 2007. Mouse iPSCs demonstrate important characteristics of pluripotent stem cells, including expressing stem cell markers, forming tumors containing cells from all three germ layers, and being able to contribute to many different tissues when injected into mouse embryos at a very early stage in development. Human iPSCs also express stem cell markers and are capable of generating cells characteristic of all three germ layers.

Although additional research is needed, iPSCs are already useful tools for drug development and modeling of diseases, and scientists hope to use them in transplantation medicine. Viruses are currently used to introduce the reprogramming factors into adult cells, and this process must be carefully controlled and tested before the technique can lead to useful treatment for humans. In animal studies, the virus used to introduce the stem cell factors sometimes causes cancers. Researchers are currently investigating non-viral delivery strategies. In any case, this breakthrough discovery has created a powerful new way to "de-differentiate" cells whose developmental fates had been previously assumed to be determined. In addition, tissues derived from iPSCs will be a nearly identical match to the cell donor and thus probably avoid rejection by the immune system. The iPSC strategy creates pluripotent stem cells that, together with studies of other types of pluripotent stem cells, will help researchers learn how to reprogram cells to repair damaged tissues in the human body.

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A bone is a rigid organ that constitutes part of the vertebral skeleton. Bones support and protect the various organs of the body, produce red and white blood cells, store minerals and also enable mobility as well as support for the body. Bone tissue is a type of dense connective tissue. Bones come in a variety of shapes and sizes and have a complex internal and external structure. They are lightweight yet strong and hard, and serve multiple functions. Mineralized osseous tissue, or bone tissue, is of two types, cortical and cancellous, and gives a bone rigidity and a coral-like three-dimensional internal structure. Other types of tissue found in bones include marrow, endosteum, periosteum, nerves, blood vessels and cartilage.

Bone is an active tissue composed of different types of bone cells. Osteoblasts are involved in the creation and mineralisation of bone; osteocytes and osteoclasts are involved in the reabsorption of bone tissue. The mineralised matrix of bone tissue has an organic component of mainly collagen called ossein and an inorganic component of bone mineral made up of various salts.

In the human body at birth, there are over 270 bones,[1] but many of these fuse together during development, leaving a total of 206 separate bones in the adult,[2] not counting numerous small sesamoid bones. The largest bone in the body is the thigh-bone (femur) and the smallest is the stapes in the middle ear.

Bone is not a uniformly solid material, but is mostly a matrix. The primary tissue of bone, bone tissue (osseous tissue), is relatively hard and lightweight. Its matrix is mostly made up of a composite material incorporating the inorganic mineral calcium phosphate in the chemical arrangement termed calcium hydroxylapatite (this is the bone mineral that gives bones their rigidity) and collagen, an elastic protein which improves fracture resistance.[3] Bone is formed by the hardening of this matrix around entrapped cells. When these cells become entrapped from osteoblasts they become osteocytes.[citation needed]

The hard outer layer of bones is composed of cortical bone also called compact bone. Cortical referring to the outer (cortex) layer. The hard outer layer gives bone its smooth, white, and solid appearance, and accounts for 80% of the total bone mass of an adult human skeleton.[citation needed] However, that proportion may be much lower, especially in marine mammals and marine turtles, or in various Mesozoic marine reptiles, such as ichthyosaurs,[4] among others.[5]

Cortical bone consists of multiple microscopic columns, each called an osteon. Each column is multiple layers of osteoblasts and osteocytes around a central canal called the Haversian canal. Volkmann's canals at right angles connect the osteons together. The columns are metabolically active, and as bone is reabsorbed and created the nature and location of the cells within the osteon will change. Cortical bone is covered by a periosteum on its outer surface, and an endosteum on its inner surface. The endosteum is the boundary between the cortical bone and the cancellous bone.

Filling the interior of the bone is the cancellous bone also known as trabecular or spongy bone tissue. It is an open cell porous network. Thin formations of osteoblasts covered in endosteum create an irregular network of spaces. Within these spaces are bone marrow and hematopoietic stem cells that give rise to platelets, red blood cells and white blood cells. Trabecular marrow is composed of a network of rod- and plate-like elements that make the overall organ lighter and allow room for blood vessels and marrow. Trabecular bone accounts for the remaining 20% of total bone mass but has nearly ten times the surface area of compact bone.[8]

Bone marrow, also known as myeloid tissue, can be found in almost any bone that holds cancellous tissue. In newborns, all such bones are filled exclusively with red marrow, but as the child ages it is mostly replaced by yellow, or fatty marrow. In adults, red marrow is mostly found in the bone marrow of the femur, the ribs, the vertebrae and pelvic bones.[citation needed]

Bone is a metabolically active tissue composed of several types of cells. These cells include osteoblasts, which are involved in the creation and mineralization of bone tissue, osteocytes, and osteoclasts, which are involved in the reabsorption of bone tissue. Osteoblasts and osteocytes are derived from osteoprogenitor cells, but osteoclasts are derived from the same cells that differentiate to form macrophages and monocytes. Within the marrow of the bone there are also hematopoietic stem cells. These cells give rise to other cells, including white blood cells, red blood cells, and platelets.

Bones consist of living cells embedded in a mineralized organic matrix. This matrix consists of organic components, mainly collagen "organic" referring to materials produced as a result of the human body and inorganic components, primarily hydroxyapatite and other salts of calcium and phosphate. Above 30% of the acellular part of bone consists of the organic components, and 70% of salts. The strands of collagen give bone its tensile strength, and the interspersed crystals of hydroxyapatite give bone its compressional strength. These effects are synergistic.

The inorganic composition of bone (bone mineral) is primarily formed from salts of calcium and phosphate, the major salt being hydroxyapatite (Ca10(PO4)6(OH)2). The exact composition of the matrix may change over time and with nutrition, with the ratio of calcium to phosphate varying between 1.3 and 2.0 (per weight), and trace minerals such as magnesium, sodium, potassium and carbonate also being found.

The organic part of matrix is mainly composed of Type I collagen. Collagen composes 9095% of the organic matrix, with remainder of the matrix being a homogenous liquid called ground substance consisting of proteoglycans such as hyaluronic acid and chondroitin sulfate. Collagen consists of strands of repeating units, which give bone tensile strength, and are arranged in an overlapping fashion that prevents shear stress. The function of ground substance is not fully known. Two types of bone can be identified microscopically according to the arrangement of collagen:

Woven bone is produced when osteoblasts produce osteoid rapidly, which occurs initially in all fetal bones, but is later replaced by more resilient lamellar bone. In adults woven bone is created after fractures or in Paget's disease. Woven bone is weaker, with a smaller number of randomly oriented collagen fibers, but forms quickly; it is for this appearance of the fibrous matrix that the bone is termed woven. It is soon replaced by lamellar bone, which is highly organized in concentric sheets with a much lower proportion of osteocytes to surrounding tissue. Lamellar bone, which makes its first appearance in humans in the fetus during the third trimester,[16] is stronger and filled with many collagen fibers parallel to other fibers in the same layer (these parallel columns are called osteons). In cross-section, the fibers run in opposite directions in alternating layers, much like in plywood, assisting in the bone's ability to resist torsion forces. After a fracture, woven bone forms initially and is gradually replaced by lamellar bone during a process known as "bony substitution." Compared to woven bone, lamellar bone formation takes place more slowly. The orderly deposition of collagen fibers restricts the formation of osteoid to about 1 to 2m per day. Lamellar bone also requires a relatively flat surface to lay the collagen fibers in parallel or concentric layers.[citation needed]

The extracellular matrix of bone is laid down by osteoblasts, which secrete both collagen and ground substance. These synthesise collagen within the cell, and then secrete collagen fibrils. The collagen fibres rapidly polymerise to form collagen strands. At this stage they are not yet mineralised, and are called "osteoid". Around the strands calcium and phosphate precipitate on the surface of these strands, within a days to weeks becoming crystals of hydroxyapatite.

In order to mineralise the bone, the osteoblasts secrete vesicles containing alkaline phosphatase. This cleaves the phosphate groups and acts as the foci for calcium and phosphate deposition. The vesicles then rupture and act as a centre for crystals to grow on. More particularly, bone mineral is formed from globular and plate structures.[17][18]

There are five types of bones in the human body: long, short, flat, irregular, and sesamoid.[19]

In the study of anatomy, anatomists use a number of anatomical terms to describe the appearance, shape and function of bones. Other anatomical terms are also used to describe the location of bones. Like other anatomical terms, many of these derive from Latin and Greek. Some anatomists still use Latin to refer to bones. The term "osseous", and the prefix "osteo-", referring to things related to bone, are still used commonly today.

Some examples of terms used to describe bones include the term "foramen" to describe a hole through which something passes, and a "canal" or "meatus" to describe a tunnel-like structure. A protrusion from a bone can be called a number of terms, including a "condyle", "crest", "spine", "eminence", "tubercle" or "tuberosity", depending on the protrusion's shape and location. In general, long bones are said to have a "head", "neck", and "body".

When two bones join together, they are said to "articulate". If the two bones have a fibrous connection and are relatively immobile, then the joint is called a "suture".

The formation of bone is called ossification. During the fetal stage of development this occurs by two processes, Intramembranous ossification and endochondral ossification.[citation needed] Intramembranous ossification involves the creation of bone from connective tissue, whereas in the process of endochondral ossification bone is created from cartilage.

Intramembranous ossification mainly occurs during formation of the flat bones of the skull but also the mandible, maxilla, and clavicles; the bone is formed from connective tissue such as mesenchyme tissue rather than from cartilage. The steps in intramembranous ossification are:[citation needed]

Endochondral ossification, on the other hand, occurs in long bones and most of the rest of the bones in the body; it involves an initial hyaline cartilage that continues to grow. The steps in endochondral ossification are:[citation needed]

Endochondral ossification begins with points in the cartilage called "primary ossification centers." They mostly appear during fetal development, though a few short bones begin their primary ossification after birth. They are responsible for the formation of the diaphyses of long bones, short bones and certain parts of irregular bones. Secondary ossification occurs after birth, and forms the epiphyses of long bones and the extremities of irregular and flat bones. The diaphysis and both epiphyses of a long bone are separated by a growing zone of cartilage (the epiphyseal plate). When the child reaches skeletal maturity (18 to 25 years of age), all of the cartilage is replaced by bone, fusing the diaphysis and both epiphyses together (epiphyseal closure).[citation needed] In the upper limbs, only the diaphyses of the long bones and scapula are ossified. The epiphyses, carpal bones, coracoid process, medial border of the scapula, and acromion are still cartilaginous.[21]

The following steps are followed in the conversion of cartilage to bone:

Bones have a variety of functions:

Bones serve a variety of mechanical functions. Together the bones in the body form the skeleton. They provide a frame to keep the body supported, and an attachment point for skeletal muscles, tendons, ligaments and joints, which function together to generate and transfer forces so that individual body parts or the whole body can be manipulated in three-dimensional space (the interaction between bone and muscle is studied in biomechanics).

Bones protect internal organs, such as the skull protecting the brain or the ribs protecting the heart and lungs. Because of the way that bone is formed, bone has a high compressive strength of about 170 MPa (1800 kgf/cm),[3] poor tensile strength of 104121 MPa, and a very low shear stress strength (51.6 MPa).[23][24] This means that bone resists pushing(compressional) stress well, resist pulling(tensional) stress less well, but only poorly resists shear stress (such as due to torsional loads). While bone is essentially brittle, bone does have a significant degree of elasticity, contributed chiefly by collagen. The macroscopic yield strength of cancellous bone has been investigated using high resolution computer models.[25]

Mechanically, bones also have a special role in hearing. The ossicles are three small bones in the middle ear which are involved in sound transduction.

Cancellous bones contain bone marrow. Bone marrow produces blood cells in a process called hematopoiesis.[26] Blood cells that are created in bone marrow include red blood cells, platelets and white blood cells. Progenitor cells such as the hematopoietic stem cell divide in a process called mitosis to produce precursor cells. These include precursors which eventually give rise to white blood cells, and erythroblasts which give rise to red blood cells. Unlike red and white blood cells, created by mitosis, platelets are shed from very large cells called megakaryocytes. This process of progressive differentiation occurs within the bone marrow. After the cells are matured, they enter the circulation. Every day, over 2.5 billion red blood cells and platelets, and 50100 billion granulocytes are produced in this way.

As well as creating cells, bone marrow is also one of the major sites where defective or aged red blood cells are destroyed.

Bone is constantly being created and replaced in a process known as remodeling. This ongoing turnover of bone is a process of resorption followed by replacement of bone with little change in shape. This is accomplished through osteoblasts and osteoclasts. Cells are stimulated by a variety of signals, and together referred to as a remodeling unit. Approximately 10% of the skeletal mass of an adult is remodelled each year.[32] The purpose of remodeling is to regulate calcium homeostasis, repair microdamaged bones from everyday stress, and also to shape and sculpt the skeleton during growth.[citation needed]. Repeated stress, such as weight-bearing exercise or bone healing, results in the bone thickening at the points of maximum stress (Wolff's law). It has been hypothesized that this is a result of bone's piezoelectric properties, which cause bone to generate small electrical potentials under stress.[33]

The action of osteoblasts and osteoclasts are controlled by a number of chemical enzymes that either promote or inhibit the activity of the bone remodeling cells, controlling the rate at which bone is made, destroyed, or changed in shape. The cells also use paracrine signalling to control the activity of each other.[citation needed] For example, the rate at which osteoclasts resorb bone is inhibited by calcitonin and osteoprotegerin. Calcitonin is produced by parafollicular cells in the thyroid gland, and can bind to receptors on osteoclasts to directly inhibit osteoclast activity. Osteoprotegerin is secreted by osteoblasts and is able to bind RANK-L, inhibiting osteoclast stimulation.[34]

Osteoblasts can also be stimulated to increase bone mass through increased secretion of osteoid and by inhibiting the ability of osteoclasts to break down osseous tissue.[citation needed] Increased secretion of osteoid is stimulated by the secretion of growth hormone by the pituitary, thyroid hormone and the sex hormones (estrogens and androgens). These hormones also promote increased secretion of osteoprotegerin.[34] Osteoblasts can also be induced to secrete a number of cytokines that promote reabsorbtion of bone by stimulating osteoclast activity and differentiation from progenitor cells. Vitamin D, parathyroid hormone and stimulation from osteocytes induce osteoblasts to increase secretion of RANK-ligand and interleukin 6, which cytokines then stimulate increased reabsorption of bone by osteoclasts. These same compounds also increase secretion of macrophage colony-stimulating factor by osteoblasts, which promotes the differentiation of progenitor cells into osteoclasts, and decrease secretion of osteoprotegerin.[citation needed]

Bone volume is determined by the rates of bone formation and bone resorption. Recent research has suggested that certain growth factors may work to locally alter bone formation by increasing osteoblast activity. Numerous bone-derived growth factors have been isolated and classified via bone cultures. These factors include insulin-like growth factors I and II, transforming growth factor-beta, fibroblast growth factor, platelet-derived growth factor, and bone morphogenetic proteins.[35] Evidence suggests that bone cells produce growth factors for extracellular storage in the bone matrix. The release of these growth factors from the bone matrix could cause the proliferation of osteoblast precursors. Essentially, bone growth factors may act as potential determinants of local bone formation.[35] Research has suggested that trabecular bone volume in postemenopausal osteoporosis may be determined by the relationship between the total bone forming surface and the percent of surface resorption.[36]

A number of diseases can affect bone, including arthritis, fractures, infections, osteoporosis and tumours. Conditions relating to bone can be managed by a variety of doctors, including rheumatologists for joints, and orthopedic surgeons, who may conduct surgery to fix broken bones. Other doctors, such as rehabilitation specialists may be involved in recovery, radiologists in interpreting the findings on imaging, and pathologists in investigating the cause of the disease, and family doctors may play a role in preventing complications of bone disease such as osteoporosis.

When a doctor sees a patient, a history and exam will be taken. Bones are then often imaged, called radiography. This might include ultrasound X-ray, CT scan, MRI scan and other imaging such as a Bone scan, which may be used to investigate cancer. Other tests such as a blood test for autoimmune markers may be taken, or a synovial fluid aspirate may be taken.

In normal bone, fractures occur when there is significant force applied, or repetitive trauma over a long time. Fractures can also occur when a bone is weakened, such as with osteoporosis, or when there is a structural problem, such as when the bone remodels excessively (such as Paget's disease) or is the site of the growth of cancer. Common fractures include wrist fractures and hip fractures, associated with osteoporosis, vertebral fractures associated with high-energy trauma and cancer, and fractures of long-bones. Not all fractures are painful. When serious, depending on the fractures type and location, complications may include flail chest, compartment syndromes or fat embolism. Compound fractures involve the bone's penetration through the skin.

Fractures and their underlying causes can be investigated by X-rays, CT scans and MRIs. Fractures are described by their location and shape, and several classification systems exist, depending on the location of the fracture. A common long bone fracture in children is a SalterHarris fracture.[39] When fractures are managed, pain relief is often given, and the fractured area is often immobilised. This is to promote bone healing. In addition, surgical measures such as internal fixation may be used. Because of the immobilisation, people with fractures are often advised to undergo rehabilitation.

There are several types of tumour that can affect bone; examples of benign bone tumours include osteoma, osteoid osteoma, osteochondroma, osteoblastoma, enchondroma, giant cell tumor of bone, aneurysmal bone cyst, and fibrous dysplasia of bone.

Cancer can arise in bone tissue, and bones are also a common site for other cancers to spread (metastasise) to. Cancers that arise in bone are called "primary" cancers, although such cancers are rare. Metastases within bone are "secondary" cancers, with the most common being breast cancer, lung cancer, prostate cancer, thyroid cancer, and kidney cancer. Secondary cancers that affect bone can either destroy bone (called a "lytic" cancer) or create bone (a "sclerotic" cancer). Cancers of the bone marrow inside the bone can also affect bone tissue, examples including leukemia and multiple myeloma. Bone may also be affected by cancers in other parts of the body. Cancers in other parts of the body may release parathyroid hormone or parathyroid hormone-related peptide. This increases bone reabsorption, and can lead to bone fractures.

Bone tissue that is destroyed or altered as a result of cancers is distorted, weakened, and more prone to fracture. This may lead to compression of the spinal cord, destruction of the marrow resulting in bruising, bleeding and immunosuppression, and is one cause of bone pain. If the cancer is metastatic, then there might be other symptoms depending on the site of the original cancer. Some bone cancers can also be felt.

Cancers of the bone are managed according to their type, their stage, prognosis, and what symptoms they cause. Many primary cancers of bone are treated with radiotherapy. Cancers of bone marrow may be treated with chemotherapy, and other forms of targeted therapy such as immunotherapy may be used.Palliative care, which focuses on maximising a person's quality of life, may play a role in management, particularly if the likelihood of survival within five years is poor.

Osteoporosis is a disease of bone where there is reduced bone mineral density, increasing the likelihood of fractures. Osteoporosis is defined by the World Health Organization in women as a bone mineral density 2.5 standard deviations below peak bone mass, relative to the age and sex-matched average, as measured by Dual energy X-ray absorptiometry, with the term "established osteoporosis" including the presence of a fragility fracture.[43] Osteoporosis is most common in women after menopause, when it is called "postmenopausal osteoporosis", but may develop in men and premenopausal women in the presence of particular hormonal disorders and other chronic diseases or as a result of smoking and medications, specifically glucocorticoids. Osteoporosis usually has no symptoms until a fracture occurs. For this reason, DEXA scans are often done in people with one or more risk factors, who have developed osteoporosis and be at risk of fracture.

Osteoporosis treatment includes advice to stop smoking, decrease alcohol consumption, exercise regularly, and have a healthy diet. Calcium supplements may also be advised, as may Vitamin D. When medication is used, it may include bisphosphonates, Strontium ranelate, and osteoporosis may be one factor considered when commencing Hormone replacement therapy.[44]

The study of bones and teeth is referred to as osteology. It is frequently used in anthropology, archeology and forensic science for a variety of tasks. This can include determining the nutritional, health, age or injury status of the individual the bones were taken from. Preparing fleshed bones for these types of studies can involve the process of maceration.

Typically anthropologists and archeologists study bone tools made by Homo sapiens and Homo neanderthalensis. Bones can serve a number of uses such as projectile points or artistic pigments, and can also be made from external bones such as antlers.

Bird skeletons are very lightweight. Their bones are smaller and thinner, to aid flight. Among mammals, bats come closest to birds in terms of bone density, suggesting that small dense bones are a flight adaptation. Many bird bones have little marrow due to their being hollow.[45]

A bird's beak is primarily made of bone as projections of the mandibles which are covered in keratin.

A deer's antlers are composed of bone which is an unusual example of bone being outside the skin of the animal once the velvet is shed.[46]

The extinct predatory fish Dunkleosteus had sharp edges of hard exposed bone along its jaws.[citation needed]

Many animals possess an exoskeleton that is not made of bone, These include insects and crustaceans.

Bones from slaughtered animals have a number of uses. In prehistoric times, they have been used for making bone tools. They have further been used in bone carving, already important in prehistoric art, and also in modern time as crafting materials for buttons, beads, handles, bobbins, calculation aids, head nuts, dice, poker chips, pick-up sticks, ornaments, etc. A special genre is scrimshaw.

Bone glue can be made by prolonged boiling of ground or cracked bones, followed by filtering and evaporation to thicken the resulting fluid. Historically once important, bone glue and other animal glues today have only a few specialized uses, such as in antiques restoration. Essentially the same process, with further refinement, thickening and drying, is used to make gelatin.

Broth is made by simmering several ingredients for a long time, traditionally including bones.

Ground bones are used as an organic phosphorus-nitrogen fertilizer and as additive in animal feed. Bones, in particular after calcination to bone ash, are used as source of calcium phosphate for the production of bone china and previously also phosphorus chemicals.[citation needed]

Bone char, a porous, black, granular material primarily used for filtration and also as a black pigment, is produced by charring mammal bones.

Oracle bone script was a writing system used in Ancient china based on inscriptions in bones.

To point the bone at someone is considered bad luck in some cultures, such as Australian aborigines, such as by the Kurdaitcha.

Osteopathic medicine is a school of medical thought originally developed based on the idea of the link between the musculoskeletal system and overall health, but now very similar to mainstream medicine. As of 2012[update], over 77,000 physicians in the United States are trained in Osteopathic medicine colleges.[47]

The wishbones of fowl have been used for divination, and are still customarily used in a tradition to determine which one of two people pulling on either prong of the bone may make a wish.

Various cultures throughout history have adopted the custom of shaping an infant's head by the practice of artificial cranial deformation. A widely practised custom in China was that of foot binding to limit the normal growth of the foot.

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This article is about the medical therapy. For the cell type, see Stem cell.

Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition.

Bone marrow transplant is the most widely used stem-cell therapy, but some therapies derived from umbilical cord blood are also in use. Research is underway to develop various sources for stem cells, and to apply stem-cell treatments for neurodegenerative diseases and conditions such as diabetes, heart disease, and other conditions.

Stem-cell therapy has become controversial following developments such as the ability of scientists to isolate and culture embryonic stem cells, to create stem cells using somatic cell nuclear transfer and their use of techniques to create induced pluripotent stem cells. This controversy is often related to abortion politics and to human cloning. Additionally, efforts to market treatments based on transplant of stored umbilical cord blood have been controversial.

For over 30 years, bone marrow has been used to treat cancer patients with conditions such as leukaemia and lymphoma; this is the only form of stem-cell therapy that is widely practiced.[1][2][3] During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents, however, cannot discriminate between the leukaemia or neoplastic cells, and the hematopoietic stem cells within the bone marrow. It is this side effect of conventional chemotherapy strategies that the stem-cell transplant attempts to reverse; a donor's healthy bone marrow reintroduces functional stem cells to replace the cells lost in the host's body during treatment. The transplanted cells also generate an immune response that helps to kill off the cancer cells; this process can go too far, however, leading to graft vs host disease, the most serious side effect of this treatment.[4]

Another stem-cell therapy called Prochymal, was conditionally approved in Canada in 2012 for the management of acute graft-vs-host disease in children who are unresponsive to steroids.[5] It is an allogenic stem therapy based on mesenchymal stem cells (MSCs) derived from the bone marrow of adult donors. MSCs are purified from the marrow, cultured and packaged, with up to 10,000 doses derived from a single donor. The doses are stored frozen until needed.[6]

The FDA has approved five hematopoietic stem-cell products derived from umbilical cord blood, for the treatment of blood and immunological diseases.[7]

In 2014, the European Medicines Agency recommended approval of Holoclar, a treatment involving stem cells, for use in the European Union. Holoclar is used for people with severe limbal stem cell deficiency due to burns in the eye.[8]

In March 2016 GlaxoSmithKline's Strimvelis (GSK2696273) therapy for the treatment ADA-SCID was recommended for EU approval.[9]

Stem cells are being studied for a number of reasons. The molecules and exosomes released from stem cells are also being studied in an effort to make medications.[10]

Research has been conducted on the effects of stem cells on animal models of brain degeneration, such as in Parkinson's, Amyotrophic lateral sclerosis, and Alzheimer's disease.[11][12][13] There have been preliminary studies related to multiple sclerosis.[14][15]

Healthy adult brains contain neural stem cells which divide to maintain general stem-cell numbers, or become progenitor cells. In healthy adult laboratory animals, progenitor cells migrate within the brain and function primarily to maintain neuron populations for olfaction (the sense of smell). Pharmacological activation of endogenous neural stem cells has been reported to induce neuroprotection and behavioral recovery in adult rat models of neurological disorder.[16][17][18]

Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and oligodendrocytes within the brain. A small clinical trial was underway in Scotland in 2013, in which stem cells were injected into the brains of stroke patients.[19]

Clinical and animal studies have been conducted into the use of stem cells in cases of spinal cord injury.[20][21][22]

The pioneering work[23] by Bodo-Eckehard Strauer has now been discredited by the identification of hundreds of factual contradictions.[24] Among several clinical trials that have reported that adult stem-cell therapy is safe and effective, powerful effects have been reported from only a few laboratories, but this has covered old[25] and recent[26] infarcts as well as heart failure not arising from myocardial infarction.[27] While initial animal studies demonstrated remarkable therapeutic effects,[28][29] later clinical trials achieved only modest, though statistically significant, improvements.[30][31] Possible reasons for this discrepancy are patient age,[32] timing of treatment[33] and the recent occurrence of a myocardial infarction.[34] It appears that these obstacles may be overcome by additional treatments which increase the effectiveness of the treatment[35] or by optimizing the methodology although these too can be controversial. Current studies vary greatly in cell-procuring techniques, cell types, cell-administration timing and procedures, and studied parameters, making it very difficult to make comparisons. Comparative studies are therefore currently needed.

Stem-cell therapy for treatment of myocardial infarction usually makes use of autologous bone-marrow stem cells (a specific type or all), however other types of adult stem cells may be used, such as adipose-derived stem cells.[36] Adult stem cell therapy for treating heart disease was commercially available in at least five continents as of 2007.[citation needed]

Possible mechanisms of recovery include:[11]

It may be possible to have adult bone-marrow cells differentiate into heart muscle cells.[11]

The first successful integration of human embryonic stem cell derived cardiomyocytes in guinea pigs (mouse hearts beat too fast) was reported in August 2012. The contraction strength was measured four weeks after the guinea pigs underwent simulated heart attacks and cell treatment. The cells contracted synchronously with the existing cells, but it is unknown if the positive results were produced mainly from paracrine as opposed to direct electromechanical effects from the human cells. Future work will focus on how to get the cells to engraft more strongly around the scar tissue. Whether treatments from embryonic or adult bone marrow stem cells will prove more effective remains to be seen.[37]

In 2013 the pioneering reports of powerful beneficial effects of autologous bone marrow stem cells on ventricular function were found to contain "hundreds" of discrepancies.[38] Critics report that of 48 reports there seemed to be just five underlying trials, and that in many cases whether they were randomized or merely observational accepter-versus-rejecter, was contradictory between reports of the same trial. One pair of reports of identical baseline characteristics and final results, was presented in two publications as, respectively, a 578 patient randomized trial and as a 391 patient observational study. Other reports required (impossible) negative standard deviations in subsets of patients, or contained fractional patients, negative NYHA classes. Overall there were many more patients published as having receiving stem cells in trials, than the number of stem cells processed in the hospital's laboratory during that time. A university investigation, closed in 2012 without reporting, was reopened in July 2013.[39]

One of the most promising benefits of stem cell therapy is the potential for cardiac tissue regeneration to reverse the tissue loss underlying the development of heart failure after cardiac injury.[40]

Initially, the observed improvements were attributed to a transdifferentiation of BM-MSCs into cardiomyocyte-like cells.[28] Given the apparent inadequacy of unmodified stem cells for heart tissue regeneration, a more promising modern technique involves treating these cells to create cardiac progenitor cells before implantation to the injured area.[41]

The specificity of the human immune-cell repertoire is what allows the human body to defend itself from rapidly adapting antigens. However, the immune system is vulnerable to degradation upon the pathogenesis of disease, and because of the critical role that it plays in overall defense, its degradation is often fatal to the organism as a whole. Diseases of hematopoietic cells are diagnosed and classified via a subspecialty of pathology known as hematopathology. The specificity of the immune cells is what allows recognition of foreign antigens, causing further challenges in the treatment of immune disease. Identical matches between donor and recipient must be made for successful transplantation treatments, but matches are uncommon, even between first-degree relatives. Research using both hematopoietic adult stem cells and embryonic stem cells has provided insight into the possible mechanisms and methods of treatment for many of these ailments.[citation needed]

Fully mature human red blood cells may be generated ex vivo by hematopoietic stem cells (HSCs), which are precursors of red blood cells. In this process, HSCs are grown together with stromal cells, creating an environment that mimics the conditions of bone marrow, the natural site of red-blood-cell growth. Erythropoietin, a growth factor, is added, coaxing the stem cells to complete terminal differentiation into red blood cells.[42] Further research into this technique should have potential benefits to gene therapy, blood transfusion, and topical medicine.

In 2004, scientists at King's College London discovered a way to cultivate a complete tooth in mice[43] and were able to grow bioengineered teeth stand-alone in the laboratory. Researchers are confident that the tooth regeneration technology can be used to grow live teeth in human patients.

In theory, stem cells taken from the patient could be coaxed in the lab turning into a tooth bud which, when implanted in the gums, will give rise to a new tooth, and would be expected to be grown in a time over three weeks.[44] It will fuse with the jawbone and release chemicals that encourage nerves and blood vessels to connect with it. The process is similar to what happens when humans grow their original adult teeth. Many challenges remain, however, before stem cells could be a choice for the replacement of missing teeth in the future.[45][46]

Research is ongoing in different fields, alligators which are polyphyodonts grow up to 50 times a successional tooth (a small replacement tooth) under each mature functional tooth for replacement once a year.[47]

Heller has reported success in re-growing cochlea hair cells with the use of embryonic stem cells.[48]

Since 2003, researchers have successfully transplanted corneal stem cells into damaged eyes to restore vision. "Sheets of retinal cells used by the team are harvested from aborted fetuses, which some people find objectionable." When these sheets are transplanted over the damaged cornea, the stem cells stimulate renewed repair, eventually restore vision.[49] The latest such development was in June 2005, when researchers at the Queen Victoria Hospital of Sussex, England were able to restore the sight of forty patients using the same technique. The group, led by Sheraz Daya, was able to successfully use adult stem cells obtained from the patient, a relative, or even a cadaver. Further rounds of trials are ongoing.[50]

In April 2005, doctors in the UK transplanted corneal stem cells from an organ donor to the cornea of Deborah Catlyn, a woman who was blinded in one eye when acid was thrown in her eye at a nightclub. The cornea, which is the transparent window of the eye, is a particularly suitable site for transplants. In fact, the first successful human transplant was a cornea transplant. The absence of blood vessels within the cornea makes this area a relatively easy target for transplantation. The majority of corneal transplants carried out today are due to a degenerative disease called keratoconus.

The University Hospital of New Jersey reports that the success rate for growth of new cells from transplanted stem cells varies from 25 percent to 70 percent.[51]

In 2014, researchers demonstrated that stem cells collected as biopsies from donor human corneas can prevent scar formation without provoking a rejection response in mice with corneal damage.[52]

In January 2012, The Lancet published a paper by Steven Schwartz, at UCLA's Jules Stein Eye Institute, reporting two women who had gone legally blind from macular degeneration had dramatic improvements in their vision after retinal injections of human embryonic stem cells.[53]

In June 2015, the Stem Cell Ophthalmology Treatment Study (SCOTS), the largest adult stem cell study in ophthalmology ( http://www.clinicaltrials.gov NCT # 01920867) published initial results on a patient with optic nerve disease who improved from 20/2000 to 20/40 following treatment with bone marrow derived stem cells.[54]

Diabetes patients lose the function of insulin-producing beta cells within the pancreas.[55] In recent experiments, scientists have been able to coax embryonic stem cell to turn into beta cells in the lab. In theory if the beta cell is transplanted successfully, they will be able to replace malfunctioning ones in a diabetic patient.[56]

Human embryonic stem cells may be grown in cell culture and stimulated to form insulin-producing cells that can be transplanted into the patient.

However, clinical success is highly dependent on the development of the following procedures:[11]

Clinical case reports in the treatment orthopaedic conditions have been reported. To date, the focus in the literature for musculoskeletal care appears to be on mesenchymal stem cells. Centeno et al. have published MRI evidence of increased cartilage and meniscus volume in individual human subjects.[57][58] The results of trials that include a large number of subjects, are yet to be published. However, a published safety study conducted in a group of 227 patients over a 3-4-year period shows adequate safety and minimal complications associated with mesenchymal cell transplantation.[59]

Wakitani has also published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects.[60]

Stem cells can also be used to stimulate the growth of human tissues. In an adult, wounded tissue is most often replaced by scar tissue, which is characterized in the skin by disorganized collagen structure, loss of hair follicles and irregular vascular structure. In the case of wounded fetal tissue, however, wounded tissue is replaced with normal tissue through the activity of stem cells.[61] A possible method for tissue regeneration in adults is to place adult stem cell "seeds" inside a tissue bed "soil" in a wound bed and allow the stem cells to stimulate differentiation in the tissue bed cells. This method elicits a regenerative response more similar to fetal wound-healing than adult scar tissue formation.[61] Researchers are still investigating different aspects of the "soil" tissue that are conducive to regeneration.[61]

Culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cells (precursor cells of oocytes and spermatozoa), as evidenced by gene expression analysis.[62]

Human embryonic stem cells have been stimulated to form Spermatozoon-like cells, yet still slightly damaged or malformed.[63] It could potentially treat azoospermia.

In 2012, oogonial stem cells were isolated from adult mouse and human ovaries and demonstrated to be capable of forming mature oocytes.[64] These cells have the potential to treat infertility.

Destruction of the immune system by the HIV is driven by the loss of CD4+ T cells in the peripheral blood and lymphoid tissues. Viral entry into CD4+ cells is mediated by the interaction with a cellular chemokine receptor, the most common of which are CCR5 and CXCR4. Because subsequent viral replication requires cellular gene expression processes, activated CD4+ cells are the primary targets of productive HIV infection.[65] Recently scientists have been investigating an alternative approach to treating HIV-1/AIDS, based on the creation of a disease-resistant immune system through transplantation of autologous, gene-modified (HIV-1-resistant) hematopoietic stem and progenitor cells (GM-HSPC).[66]

On 23 January 2009, the US Food and Drug Administration gave clearance to Geron Corporation for the initiation of the first clinical trial of an embryonic stem-cell-based therapy on humans. The trial aimed evaluate the drug GRNOPC1, embryonic stem cell-derived oligodendrocyte progenitor cells, on patients with acute spinal cord injury. The trial was discontinued in November 2011 so that the company could focus on therapies in the "current environment of capital scarcity and uncertain economic conditions".[67] In 2013 biotechnology and regenerative medicine company BioTime (NYSEMKT:BTX) acquired Geron's stem cell assets in a stock transaction, with the aim of restarting the clinical trial.[68]

Scientists have reported that MSCs when transfused immediately within few hours post thawing may show reduced function or show decreased efficacy in treating diseases as compared to those MSCs which are in log phase of cell growth(fresh), so cryopreserved MSCs should be brought back into log phase of cell growth in invitro culture before these are administered for clinical trials or experimental therapies, re-culturing of MSCs will help in recovering from the shock the cells get during freezing and thawing. Various clinical trials on MSCs have failed which used cryopreserved product immediately post thaw as compared to those clinical trials which used fresh MSCs.[69]

Research currently conducted on horses, dogs, and cats can benefit the development of stem cell treatments in veterinary medicine and can target a wide range of injuries and diseases such as myocardial infarction, stroke, tendon and ligament damage, osteoarthritis, osteochondrosis and muscular dystrophy both in large animals, as well as humans.[70][71][72][73] While investigation of cell-based therapeutics generally reflects human medical needs, the high degree of frequency and severity of certain injuries in racehorses has put veterinary medicine at the forefront of this novel regenerative approach.[74] Companion animals can serve as clinically relevant models that closely mimic human disease.[75][76]

There is widespread controversy over the use of human embryonic stem cells. This controversy primarily targets the techniques used to derive new embryonic stem cell lines, which often requires the destruction of the blastocyst. Opposition to the use of human embryonic stem cells in research is often based on philosophical, moral, or religious objections.[110] There is other stem cell research that does not involve the destruction of a human embryo, and such research involves adult stem cells, amniotic stem cells, and induced pluripotent stem cells.

Stem-cell research and treatment was practiced in the People's Republic of China. The Ministry of Health of the People's Republic of China has permitted the use of stem-cell therapy for conditions beyond those approved of in Western countries. The Western World has scrutinized China for its failed attempts to meet international documentation standards of these trials and procedures.[111]

Since 2008 many universities, centers and doctors tried a diversity of methods; in Lebanon proliferation for stem cell therapy, in-vivo and in-vitro techniques were used, Thus this country is considered the launching place of the Regentime[112] procedure. http://www.researchgate.net/publication/281712114_Treatment_of_Long_Standing_Multiple_Sclerosis_with_Regentime_Stem_Cell_Technique The regenerative medicine also took place in Jordan and Egypt.[citation needed]

Stem-cell treatment is currently being practiced at a clinical level in Mexico. An International Health Department Permit (COFEPRIS) is required. Authorized centers are found in Tijuana, Guadalajara and Cancun. Currently undergoing the approval process is Los Cabos. This permit allows the use of stem cell.[citation needed]

In 2005, South Korean scientists claimed to have generated stem cells that were tailored to match the recipient. Each of the 11 new stem cell lines was developed using somatic cell nuclear transfer (SCNT) technology. The resultant cells were thought to match the genetic material of the recipient, thus suggesting minimal to no cell rejection.[113]

As of 2013, Thailand still considers Hematopoietic stem cell transplants as experimental. Kampon Sriwatanakul began with a clinical trial in October 2013 with 20 patients. 10 are going to receive stem-cell therapy for Type-2 diabetes and the other 10 will receive stem-cell therapy for emphysema. Chotinantakul's research is on Hematopoietic cells and their role for the hematopoietic system function in homeostasis and immune response.[114]

Today, Ukraine is permitted to perform clinical trials of stem-cell treatments (Order of the MH of Ukraine 630 "About carrying out clinical trials of stem cells", 2008) for the treatment of these pathologies: pancreatic necrosis, cirrhosis, hepatitis, burn disease, diabetes, multiple sclerosis, critical lower limb ischemia. The first medical institution granted the right to conduct clinical trials became the "Institute of Cell Therapy"(Kiev).

Other countries where doctors did stem cells research, trials, manipulation, storage, therapy: Brazil, Cyprus, Germany, Italy, Israel, Japan, Pakistan, Philippines, Russia, Switzerland, Turkey, United Kingdom, India, and many others.

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