Scientists unveil the UK's largest resource of human stem cells from healthy donors Science Daily The Human Induced Pluripotent Stem Cell Initiative (HipSci) project used standardised methods to generate iPSCs on a large scale to study the differences between healthy people. Reference sets of stem cells were generated from skin biopsies donated by ... and more »

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Shinya Yamanaka ( , Yamanaka Shin'ya?, born September 4, 1962) is a Japanese Nobel Prize-winning stem cell researcher.[1][2][3] He serves as the director of Center for iPS Cell (induced Pluripotent Stem Cell) Research and Application and a professor at the Institute for Frontier Medical Sciences(ja) at Kyoto University; as a senior investigator at the UCSF-affiliated J. David Gladstone Institutes in San Francisco, California; and as a professor of anatomy at University of California, San Francisco (UCSF). Yamanaka is also a past president of the International Society for Stem Cell Research (ISSCR).

He received the 2010 BBVA Foundation Frontiers of Knowledge Award in Biomedicine category. Also he received the Wolf Prize in Medicine in 2011 with Rudolf Jaenisch;[6] the Millennium Technology Prize in 2012 together with Linus Torvalds. In 2012 he and John Gurdon were awarded the Nobel Prize for Physiology or Medicine for the discovery that mature cells can be converted to stem cells.[7] In 2013 he was awarded the $3 million Breakthrough Prize in Life Sciences for his work.

Yamanaka was born in Higashisaka Japan in 1962. After graduating from Tennji High School attached to Osaka Kyoiku University,[8] he received his M.D. at Kobe University in 1987 and his PhD at Osaka City University Graduate School in 1993. After this, he went through a residency in orthopedic surgery at National Osaka Hospital and a postdoctoral fellowship at the Gladstone Institute of Cardiovascular Disease, San Francisco.

Afterwards he worked at the Gladstone Institutes in San Francisco, USA and Nara Institute of Science and Technology in Japan. Yamanaka is currently a Professor at Kyoto University, where he directs its Center for iPS Research and Application. He is also a senior investigator at the Gladstone Institutes as well as the director of the Center for iPS Cell Research and Application(ja).[9]

Between 1987 and 1989, Yamanaka was a resident in orthopedic surgery at the National Osaka Hospital. His first operation was to remove a benign tumor from his friend Shuichi Hirata, a task he could not complete after one hour when a skilled surgeon would have taken ten minutes or so. Some seniors referred to him as "Jamanaka", a pun on the Japanese word for obstacle.[10]

From 1993 to 1996, he was at the Gladstone Institute of Cardiovascular Disease. Between 1996 and 1999, he was an assistant professor at Osaka City University Medical School, but found himself mostly looking after mice in the laboratory, not doing actual research.[10]

His wife advised him to become a practicing doctor, but instead he applied for a position at the Nara Institute of Science and Technology. He stated that he could and would clarify the characteristics of embryonic stem cells, and this can-do attitude won him the job. From 19992003, he was an associate professor there, and started the research that would later win him the 2012 Nobel Prize. He became a full professor and remained at the institute in that position from 20032005. Between 2004 and 2010, Yamanaka was a professor at the Institute for Frontier Medical Sciences.[11] Currently, Yamanaka is the director and a professor at the Center for iPS Cell Research and Application at Kyoto University.

In 2006, he and his team generated induced pluripotent stem cells (iPS cells) from adult mouse fibroblasts.[1] iPS cells closely resemble embryonic stem cells, the in vitro equivalent of the part of the blastocyst (the embryo a few days after fertilization) which grows to become the embryo proper. They could show that his iPS cells were pluripotent, i.e. capable of generating all cell lineages of the body. Later he and his team generated iPS cells from human adult fibroblasts,[2] again as the first group to do so. A key difference from previous attempts by the field was his team's use of multiple transcription factors, instead of transfecting one transcription factor per experiment. They started with 24 transcription factors known to be important in the early embryo, but could in the end reduce it to 4 transcription factors Sox2, Oct4, Klf4 and c-Myc.[1]

Yamanaka practiced judo (2nd Dan black belt) and played rugby as a university student. He also has a history of running marathons. After a 20-year gap, he competed in the inaugural Osaka Marathon in 2011 as a charity runner with a time of 4:29:53. He also took part in the 2012 Kyoto Marathon to raise money for iPS research, finishing in 4:03:19. He also ran in the second Osaka Marathon on November 25, 2012.[12]

In 2007, Yamanaka was recognized as a "Person Who Mattered" in the Time Person of the Year edition of Time Magazine.[13] Yamanaka was also nominated as a 2008 Time 100 Finalist.[14] In June 2010, Yamanaka was awarded the Kyoto Prize for reprogramming adult skin cells to pluripotential precursors. Yamanaka developed the method as an alternative to embryonic stem cells, thus circumventing an approach in which embryos would be destroyed.

In May 2010, Yamanaka was given "Doctor of Science honorary degree" by Mount Sinai School of Medicine.[15]

In September 2010, he was awarded the Balzan Prize for his work on biology and stem cells.[16]

Yamanaka has been listed as one of the 15 Asian Scientists To Watch by Asian Scientist magazine on May 15, 2011.[17][18] In June 2011, he was awarded the inaugural McEwen Award for Innovation; he shared the $100,000 prize with Kazutoshi Takahashi(ja), who was the lead author on the paper describing the generation of induced pluripotent stem cells.[19]

In June 2012, he was awarded the Millennium Technology Prize for his work in stem cells.[20] He shared the 1.2 million euro prize with Linus Torvalds, the creator of the Linux kernel.

In October 2012, he and fellow stem cell researcher John Gurdon were awarded the Nobel Prize in Physiology or Medicine "for the discovery that mature cells can be reprogrammed to become pluripotent."[21]

The 2012 Nobel Prize in Physiology or Medicine was awarded jointly to Sir John B. Gurdon and Shinya Yamanaka "for the discovery that mature cells can be reprogrammed to become pluripotent."[22]

There are different types of stem cells

. These are some types of cells that will help in understanding the material.

totipotency remains through the first few cell divisions ex. the fertilised egg

The early embryo consists mainly of pluripotent stem cells

ex) blood multipotent cells can develop into various blood cells

Theoretically patient-specific transplantations possible

Much research done Immune rejection reducible via stem cell bank

Pluripotent

Abnormal aging

No immune rejection Safe (clinical trials)

The prevalent view during the early 20th century was that mature cells were permanently locked into the differentiated state and cannot return to a fully immature, pluripotent stem cell state. They thought that cellular differentiation can only be a unidirectional process. Therefore, non-differentiated egg/early embryo cells can only develop into specialized cells. However, stem cells with limited potency (adult stem cells) remain in bone marrow, intestine, skin etc. to act as a source of cell replacement.[23]

The fact that differentiated cell types had specific patterns of proteins suggested irreversible epigenetic modifications or genetic alterations to be the cause of unidirectional cell differentiation. So, cells progressively become more restricted in the differentiation potential and eventually lose pluripotency.[24]

In 1962, John B. Gurdon demonstrated that the nucleus from a differentiated frog intestinal epithelial cell can generate a fully functional tadpole via transplantation to an enucleated egg. Gurdon used somatic cell nuclear transfer (SCNT) as a method to understand reprogramming and how cells change in specialization. He concluded that differentiated somatic cell nuclei had the potential to revert to pluripotency. This was a paradigm shift during the time. It showed that a differentiated cell nucleus has retained the capacity to successfully revert to an undifferentiated state, with the potential to restart development (pluripotent capacity).

However, the question still remained whether an intact differentiated cell could be fully reprogrammed to become pluripotent.

Shinya Yamanaka proved that introduction of a small set of transcription factors into a differentiated cell was sufficient to revert the cell to a pluripotent state. Yamanaka focused on factors that are important for maintaining pluripotency in embryonic stem (ES) cells. Knowing that transcription factors were involved in the maintenance of the pluripotent state, he selected a set of 24 ES cell transcriptional factors as candidates to reinstate pluripotency in somatic cells.

First, he collected the 24 candidate factors. When all 24 genes encoding these transcription factors were introduced into skin fibroblasts, few actually generated colonies that were remarkably similar to ES cells. Secondly, further experiments were conducted with smaller numbers of transcription factors added to identify the key factors, through a very simple and yet sensitive assay system. Lastly, he identified the four key factors. They found that 4 transcriptional factors (Myc, Oct3/4, Sox2 and Klf4) were sufficient to convert mouse embryonic or adult fibroblasts to pluripotent stem cells (capable of producing teratomas in vivo and contributing to chimeric mice).

These pluripotent cells are called iPS (induced pluripotent stem) cells; they appeared with very low frequency.

iPS cells can be selected by inserting the b-geo gene into the Fbx15 locus. The Fbx15 promoter is active in pluripotent stem cells which induce b-geo expression, which in turn gives rise to G418 resistance; this resistance helps us identify the iPS cells in a culture.

Moreover, in 2007, Yamanaka and his colleagues found iPS cells with germ line transmission (via selecting for Oct4 or Nanog gene). Also in 2007, they were the first to produce human iPS cells.

However, there are some difficulties to overcome. The first is the issue of the very low production rate of iPS cells, and the other is the fact that the 4 transcriptional factors are shown to be oncogenic.

Nonetheless, this is a truly fundamental discovery. This was the first time an intact differentiated somatic cell could be reprogrammed to become pluripotent. This opened up a completely new research field.

In July 2014, a scandal regarding the research of Haruko Obokata was connected to Yamanaka. He could not find the lab notes from the period in question [25] and was made to apologise.[26][27]

Since the original discovery by Yamanaka, much further research has been done in this field, and many improvements have been made to the technology. Here we[who?] discuss the improvements made to Yamanaka's research as well as the future prospects of his findings.

1. The delivery mechanism of pluripotency factors has been improved. At first retroviral vectors, that integrate randomly in the genome and cause deregulation of genes that contribute to tumor formation, were used. However, now, non-integrating viruses, stabilised RNAs or proteins, or episomal plasmids (integration-free delivery mechanism) are used.

2. Transcription factors required for inducing pluripotency in different cell types have been identified (e.g. neural stem cells).

3. Small substitutive molecules were identified, that can substitute for the function of the transcription factors.

4. Transdifferentiation experiments were carried out. They tried to change the cell fate without proceeding through a pluripotent state. They were able to systematically identify genes that carry out transdifferentiation using combinations of transcription factors that induce cell fate switches. They found trandifferentiation within germ layer and between germ layers, e.g., exocrine cells to endocrine cells, fibroblast cells to myoblast cells, fibroblast cells to cardiomyocyte cells, fibroblast cells to neurons

5. Cell replacement therapy with iPS cells is a possibility. Stem cells can replace diseased or lost cells in degenerative disorders and they are less prone to immune rejection. However, there is a danger that it may introduce mutations or other genomic abnormalities that render it unsuitable for cell therapy. So, there are still many challenges, but it is a very exciting and promising research area. Further work is required to guarantee safety for patients.

6. Can medically use iPS cells from patients with genetic and other disorders to gain insights into the disease process. - Amyotrophic lateral sclerosis (ALS), Rett syndrome, spinal muscular atrophy (SMA), 1-antitrypsin deficiency, familial hypercholesterolemia and glycogen storage disease type 1A. - For cardiovascular disease, Timothy syndrome, LEOPARD syndrome, type 1 and 2 long QT syndrome - Alzheimers, Spinocerebellar ataxia, Huntingtons etc.

7. iPS cells provide screening platforms for development and validation of therapeutic compounds. For example, kinetin was a novel compound found in iPS cells from familial dysautonomia and beta blockers & ion channel blockers for long QT syndrome were identified with iPS cells.

Yamanaka's research has opened a new door and the world's scientists have set forth on a long journey of exploration, hoping to find our cells true potential.[28]

In 2013, iPS cells were used to generate a human vascularized and functional liver in mice in Japan. Multiple stem cells were used to differentiate the component parts of the liver, which then self-organized into the complex structure. When placed into a mouse host, the liver vessels connected to the hosts vessels and performed normal liver functions, including breaking down of drugs and liver secretions. [29]

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Kidney research leads to surprising discovery about how the heart forms Science Daily "For a long time, scientists believed that each organ developed independently of other organs, and the heart developed from certain stem cells and blood developed from blood stem cells," explained researcher Brian C. Belyea, MD, of the UVA Children's ... and more »

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Bone marrow makes our red blood cells

DENNIS KUNKEL MICROSCOPY/SPL

By Helen Thomson

Scientists have engineered a bone-like implant to have its own working marrow that is capable of producing healthy blood. The implant may help treat several blood and immune disorders without the side effects of current treatments.

Bone marrow is the spongy tissue present inside the centre of bones. One of its jobs is to produce red blood cells from stem cells. Bone marrow transplants are sometimes needed to treat immune diseases that attack these stem cells, or in certain types of anaemia, in which the body cant make enough blood cells or clotting factors.

Such transplants involve replacing damaged marrow with bone marrow stem cells from a healthy donor. But first, the recipient must have their own bone marrow stem cells wiped out to make room for the transplanted donor cells. This is done using radiation and drugs, which can have serious side effects, such as nausea and loss of fertility.

To get round this problem, Shyni Varghese at the University of California, San Diego, and her colleagues have engineered an implant that resembles real bone. It provides a home for donor cells to grow and proliferate, bypassing the need for any drug and radiation treatment.

The implant has two main sections: an outer bone-like structure and an inner marrow, both engineered from a hydrogel matrix. Within the outer structure, calcium phosphate minerals help stem cells from the host grow into cells that help build bone. The inner matrix creates a home for donor bone marrow stem cells.

When placed beneath the skin in mice, the implant grew into a bone-like structure and produced a working marrow. Blood cells made by the donor stem cells inside the implant were able to get into circulation where they mixed with the hosts own blood cells. Six months later, blood cells from both the donor and host were still circulating around the body.

Its an additional accessory for the host, says Varghese. They have their own bone tissue and now an additional one that can be used if needed. Its like having more batteries for the bone.

Since the implant contributes to the hosts blood supply, rather than replacing it altogether, it cannot be used to treat people who have blood cancers, who would still need to have their own bone marrow stem cells wiped out to cure the disease.

Edward Gordon-Smith, emeritus professor of haemotology at St Georges University of London, says that the study isa splendid achievement.He says the structure could also offer a new way of studying blood stem cells and how blood disorders arise.

Journal reference: PNAS, DOI: 10.1073/pnas.1702576114

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Synthetic bone implant can make blood cells in its marrow - New Scientist

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Newswise BIRMINGHAM, Ala. The third annual Cardiovascular Tissue Engineering Symposium met at the University of Alabama at Birmingham last month, a gathering of noted physicians and scientists who share the goal of creating new tissues and new knowledge that can prevent or repair heart disease and heart attacks.

Talks ranged from the cutting-edge translational work of Phillippe Menasche, M.D., Ph.D., professor of thoracic and cardiovascular surgery, Paris Descartes University, to the basic biology research of Sean Wu, M.D., Ph.D., an associate professor of medicine, Stanford University School of Medicine. Menasches work pioneers human treatment with engineered heart tissue. Wus work opens the door to generating heart chamber-specific cardiomyocytes from human induced pluripotent stem cells, which act similarly to embryonic stem cells, having the potential to differentiate into any type of cell.

Menasche has placed engineered heart tissue derived from embryonic stem cell-derived cardiac cells onto the hearts of six heart attack patients in France in an initial safety study for this engineered tissue approach. Wu has used single-cell RNA sequencing to show 18 categories of cardiomyocytes in the heart, differing by cell type and anatomical location, even though they all derived from the same lineage.

We are creating a new community of engineer-scientists, said Jay Zhang, M.D., Ph.D., chair and professor of the UAB Department of Biomedical Engineering. In their welcoming remarks, both Selwyn Vickers, M.D., dean of the UAB School of Medicine, and Victor Dzau, M.D., professor of medicine at Duke University School of Medicine and president of the National Academy of Medicine, spoke of the growing convergence between scientists and physicians that is leading to tremendous possibilities to improve patient care.

The tissue engineering field is moving fast.

Cardiac progenitor cells that can contribute to growth or repair injury in the heart were only discovered in 2003, says symposium presenter Michael Davis, Ph.D., associate professor of Medicine, Department of Biomedical Engineering, Georgia Tech College of Engineering and Emory University School of Medicine. In 2006, the Japanese scientist Shinya Yamanaka first showed how to transform adult cells into induced pluripotent stem cells. This potentially provides feedstock for tissue engineering using either pluripotent cells or specific progenitor cells for certain tissue lineages.

One example of the pace of change was given by Bjorn Knollman, M.D., Ph.D., professor of medicine and pharmacology at Vanderbilt University School of Medicine. Knollman noted an ugly truth that everyone recognized in 2013 that cardiomyocytes derived from induced pluripotent stem cells were nothing like normal adult cardiomyocytes in shape, size and function.

He described the improved steps like culturing the derived cardiomyocytes in a Matrigel mattress and giving them a 14-day hormone treatment that have led to derived cardiomyocytes with greatly improved cell volume, morphology and function. His take-home message: In just four years, from 2013 to 2017, researchers were able to remove the differences between induced pluripotent stem cell-derived cardiomyocytes and normal adult cardiomyocytes.

In other highlights of the symposium, Joo Soares, Ph.D., a research scientist for the Center for Cardiovascular Simulation, University of Texas at Austin, explained how subjecting engineered heart valve tissue to cyclic flexure as it is grown in a bioreactor leads to improved quantity, quality and distribution of collagen, as opposed to tissue that is not mechanically stressed.

Sumanth Prabhu, M.D., professor and chair of the Division of Cardiovascular Disease, UAB School of Medicine, talked about the role of immune cells in cardiac remodeling and heart failure. He noted the distinct phases after a heart attack acute inflammation and dead tissue degradation, zero to four days; the healing phase of resolution and repair, four to 14 days; and the chronic ischemic heart failure that can occur weeks to months later. Prabhu described experiments to show how specialized spleen macrophages specifically marginal-zone metallophilic macrophages migrate to the heart after a heart attack and are required for heart repair to commence.

Nenad Bursac, Ph.D., professor of Biomedical Engineering, Duke University School of Medicine, described his advances in engineering vascularized heart tissue for repair after a heart attack. Bursac said a better understanding of how to grow the tissue from heart tissue progenitor cells has allowed formation of mature giga patches up to 4 centimeters square that have good propagation of heartbeat contractions and spontaneous formation of capillaries from derived-vascular endothelial and smooth muscle cells. These patches are being tested in pigs.

Duke Universitys Victor Dzau gave a perspective of the paracrine hypothesis over the past 15 years. In 2003, researchers had seen that applying mesenchymal stem cells to a heart attack area led to improved heart function, with beneficial effects seen as early as 72 hours. However, there was little engraftment and survival of the stem cells. Thus was born the hypothesis, which has been worked out in detail since then that stem cells do their work by release of biologically active factors that act on other cells, similar to the way that paracrine hormones have their effect only in the vicinity of the gland secreting it.

Joseph Wu, M.D., Ph.D., professor of radiology, Stanford University School of Medicine, showed how heart cells derived from induced pluripotent stem cells could be used to develop personalized medicine approaches for cancer patients. The problem, he explained, is that some cancer patients are susceptible to a deadly cardiotoxicity when treated with the potent drug doxorubicin. Hence, the drug has a black box warning, the strictest warning mandated by the Food and Drug Administration. Wu was able to use a library of induced pluripotent stem cell-derived cardiomyocytes to associate certain genotypes and phenotypes with doxorubicin sensitivity, in what he called a clinical trial in a dish. From this knowledge, it will be possible to look at the transcriptome profile in patient-specific cardiomyocytes derived from induced pluripotent stem cells to predict patient-specific drug safety and efficacy, thus fulfilling the definition of precision medicine the right treatment at the right time to the right person.

In all, UABs Cardiovascular Tissue Engineering Symposium included more than 30 presentations. The entire symposium will be summarized in a paper for the journal Circulation Research, expected to be published shortly, Zhang says.

Presentations of the 2015 Cardiovascular Tissue Engineering Symposium were published in the journal Science Translational Medicine, and the presentations of the 2016 Cardiovascular Tissue Engineering Symposium were published in the journal Circulation Research.

At UAB, Zhang holds the T. Michael and Gillian Goodrich Endowed Chair of Engineering Leadership, Vickers holds the James C. Lee Jr. Endowed Chair for the Dean of the School of Medicine, and Prabhu holds the Mary Gertrude Waters Chair of Cardiovascular Medicine.

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Fixing Broken Hearts Through Tissue Engineering - Newswise (press release)

Cardiac Stem Cells Comments Off on Fixing Broken Hearts Through Tissue Engineering – Newswise (press release) | May 6th, 2017

April Stevens , WZZM 4:52 PM. EDT May 04, 2017

Nick Keizer during the donation process. He donated stem cells on his birthday, May 2, to a man in Denmark. (Photo: Courtesy of GVSU)

ALLENDALE, MICH. - A Grand Valley State University football player celebrated his birthday doing something utterly selfless -- donating stem cells to man in Denmark.

The Laker football tight end, Nick Keizer, and many of his teammates swabbed their cheeks a Michigan Blood registry drive in March 2016. At the time, Keizer said he never thought he would be a bone marrow match for someone.

"The presentation pulled at my heart and I thought, 'Why not sign up to be a donor?' Yet I also thought the odds of me actually being a match can't be that high," he said.

Being a bone marrow match is quite rare -- about a 1 in 500 chance, according to Caitlin Gallagher, community engagement representation for Michigan Blood and Be the Match.

Michigan Blood was notified in December that Keizer and the Denmark man were potential matches. Keizer was required to undergo more blood work and in February, was deemed a perfect match for a 59-year-old man in Denmark who suffered from a bone marrow disease.

Keizer's non-surgical donation took about four hours, and although he's "not a big needle guy" he went through with it all, "because, that doesn't compare to what the patient is going through."

His stem cells were sent by a volunteer courierwho flew to Denmark on May 2, Keizer's birthday.

Keizer is a Portage native, he graduate from Grand Valley on April 28 with a bachelor's degree in accounting and finance. Keizer is eligible to play one more season of football, and will finish his athletic career in the fall while pursuing a master's degree in business administration.

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April Stevensis a multi-platform producer atWZZM13. Have a news tip? Emailnews@wzzm13.com, visit ourFacebook pageorTwitter.

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April 28, 2017 Neurons (red) and muscle cells (green) produced from NMPs in the laboratory. Credit: James Briscoe, Francis Crick Institute

A study from scientists at the Francis Crick Institute, the Max-Delbrck Center for Molecular Medicine, Berlin and the University of Edinburgh sheds new light on the cells that form spinal cord, muscle and bone tissue in mammalian embryos.

This discovery paves the way for generating these tissues from stem cells in the laboratory and could lead to new ways of studying degenerative conditions such as motor neuron disease and muscular dystrophy.

In embryos, the spinal cord, muscle and skeleton are produced from a group of cells called NMPs (neuro-mesodermal progenitors). These cells are few in number and exist only for a short time in embryos, despite giving rise to many tissues in the body. Their scarcity and inaccessibility has made studying NMPs challenging. Now, by using the latest molecular techniques, the research team has for the first time deciphered gene activity in NMPs. They used an advanced technique called single-cell transcriptional profiling, which analyses individual cells to provide a detailed picture of gene activity in every cell.

The technique allowed the team to establish a molecular signature of NMPs and to show that NMPs produced from stem cells in petri dishes in the laboratory closely resemble those found in embryos. This enabled the team to use lab-grown NMPs to learn more about these cells and how they make spinal cord, muscle and bone tissue. By manipulating the cells in petri dishes and testing the function of specific genes, the researchers re-constructed the regulatory mechanism and formulated a mathematical model that explains how NMPs produce the appropriate amounts of spinal cord and musculoskeletal cells.

Dr James Briscoe, who led the research from the Francis Crick Institute said:

"For embryonic development to progress smoothly, NMPs must make the right types of cells, in the right numbers at the right time. Understanding how cells such as NMPs make decisions is therefore central to understanding embryonic development. Single cell profiling techniques, including the ones we used in this study, are giving us unprecedented insight into this problem and offering a new and fascinating view of how embryos produce the different tissues that make up adults."

First author of the study Dr Mina Gouti, from the Max-Delbrck Center for Molecular Medicine, Berlin said:

"Improving our understanding of NMPs doesn't only answer an important developmental biology question but also holds great promise for regenerative medicine. It takes us a step closer to being able to use tissue from patients with diseases that affect muscles and motor neurons in order to study the causes and progress of these diseases. Being able to grow cells in the laboratory that faithfully resemble those found in the body is crucial for this."

The paper, A gene regulatory network balances neural and mesoderm specification during vertebrate trunk development, is published in Developmental Cell.

Explore further: Researchers turn stem cells into somites, precursors to skeletal muscle, cartilage and bone

More information: Mina Gouti et al. A Gene Regulatory Network Balances Neural and Mesoderm Specification during Vertebrate Trunk Development, Developmental Cell (2017). DOI: 10.1016/j.devcel.2017.04.002

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Spinal Cord Stem Cells Comments Off on New study reveals how embryonic cells make spinal cord, muscle … – Medical Xpress | April 29th, 2017

A quick glance at your calendar will reveal that we're now in 2017. 2017, you may recall, is the year when contraversial surgeon Sergio Canavero has promised to perform the world's first human head transplant.

But just how feasible is a human head transplant? Is it the stuff of science fiction, or does it have a basis in current sceintific thinking? Read on for everything you need to know about 2017 most alarming scientific development.

A human head transplant is exactly what it sounds like taking one living head and putting it onto a new body.

But actually, thats a little misleading. In real terms, its a body transplant, as the head will be gaining a new body to control. However, as the term whole body transplant is already used to mean transferring the brain between bodies, calling it a head transplant makes it clear that the whole head is to be switched, brain included.

Until recently, a head transplant seemed totally implausible, but the Italian scientist Dr Sergio Canavero believes its possible, and intends to conduct the first surgery in 2017.

Canavero outlines the procedure in detail here, but these are the basics of the process. Remember: dont try this at home, kids.

The donor body and the head to be attached are first cooled down to 12-15C to ensure that the cells last longer than a few minutes without oxygen. The tissue around the neck is then cut, with the major blood vessels linked with tiny tubes. The spinal cord on each party is then severed cleanly with an extremely sharp blade.

"Post coma, Canavero believes the patient would immediately be able to move, feel their face and even speak with the same voice."

At this point, the head is ready to be moved, and the two ends of the spinal cord are fused using a chemical called polyethylene glycol, encouraging the cells to mesh. This chemical has been shown to prompt the growth of spinal cord nerves in animals, although Canavero suggests that introducing stem cells or olfactory ensheathing cells into the spinal cord could also be tried.

After the muscles and blood supply are successfully connected, the patient is kept in a coma for a month to limit movement of the newly fused neck, while electrodes stimulate the spinal cord to strengthen its new connections.

Following the coma, Canavero anticipates that the patient would immediately be able to move, feel their face and even speak with the same voice. He believes physiotherapy would allow the patient to walk within a year.

He explains his suggested methods in the TED talk below.

Sceptical would be a nice way of putting it. Horrified would, in most cases, be more accurate.

Dr Hunt Batjer has attracted headlines for being particularly blunt: I would not wish this on anyone. I would not allow anyone to do it to me as there are a lot of things worse than death.

Dr Jerry Silver witnessed the 1970s monkey head transplant experiment more on which later and describes the procedure as bad science, adding that just to do the experiments is unethical. This is a particular blow to Canavero, as he states that Silvers own work in reconnecting rats spinal cords should give hope to the human head transplant. Silver dismisses this: To sever a head and even contemplate the possibility of gluing axons back properly across the lesion to their neighbours is pure and utter fantasy in my opinion.

Dr Chad Gordon, professor of plastic and reconstructive surgery and neurological surgery at Johns Hopkins University, agrees that Canaveros claims are scientifically implausible. He told BuzzFeed: Theres no way hes going to hook up somebodys brain to someones spinal cord and have them be functional.

On the conservative side, were about 100 years away from being able to figure this out, he continued. If hes saying two, and hes promising a living, breathing, talking, moving human being? Hes lying.

Dr Paul Myers, associate professor of biology at the University of Minnesota at Morris, puts it even more explicitly: This procedure will not work... Try it with monkeys first. But he cant: the result would be, at best, a shambling horror, an animal driven mad with pain and terror, crippled and whimpering, and a poor advertisement for his experiment. And most likely what hed have is a collection of corpses that suffered briefly before expiring.

Others wonder whether Canavero might simply be enjoying the limelight with a PR stunt, including Dr Arthur Caplan, director of ethics at the NYU Langone Medical Centre. Describing the doctor as nuts, he explained to CNN: Their bodies would end up being overwhelmed with different pathways and chemistry than theyre used to, and theyd go crazy.

"We'll probably see a head on a robot before we see it on [another] body," he told Live Science.

Dr John Adler of Stanford University's school of medicine is slightly more optimistic... but not much more. "Conceptually, much of this could work, but the most favourable outcome will be little more than a Christopher Reeve level of function," he told Newsweek.

Canavero is aware of this criticism, claiming that silently hes received a lot of support from the medical community. Of Dr Batjers comments that the surgery would be a fate worse than death, Canavero is scathing. Hes a vascular surgeon. A vascular surgeon of the brain, yes, but he knows nothing, he argued. How can you say such a thing? Its incredible.

"The world is moving, the critics are dwindling. Of course, there will always be critics. Science teaches us that when you propose something groundbreaking, you must be confronted by criticism. If no critics really step forward, you are saying nothing special," he told Medical News Today.

Dr Canavero also believes that the operation could essentially be used to revive the dead, if brains were suitably frozen and stored. In an interview with German magazine Ooom, Canavero said: "We will try to bring the first of the company's patients back to life, not in 100 years. As soon as the first human head transplant has taken place, i.e. no later than 2018, we will be able to attempt to reawaken the first frozen head.We are currently planning the world's first brain transplant, and I consider it realistic that we will be ready in three years at the latest."

No-one has ever attempted a human head transplant before, and attempts on animals have to put it charitably had limited success.

Image: from Motherboard, uploaded under fair use from a 1959 issue of Life

The photo above really does show a dog with two heads and its not a fake. This was the work of Soviet scientist Vladimir Demikhov, and for four days the hybrid of two dogs lived as normally as such a scientific horror could be expected to. Then they died.

Demikhov tried the experiment more than 24 times, but was unable to find a way of avoiding the dogs dying shortly after surgery. Although the results are horrifying to see, Demikhovs research did pave the way for human organ transplants.

"For four days this hybrid of two dogs lived as normally as such a scientific horror could be expected to. Then they died."

But back to the topic of head transplants. The first time a straight swap was successful, was by Dr Robert White, in an experiment on a rhesus monkey in 1970. I feel the need to qualify the word successful with quotation marks, because although the monkey did live, he didnt live very long. Eight days, to be exact, and as the spinal cord wasnt attached to its new body, the monkey was paralysed for its remaining days. However, it could indeed see, hear, smell and taste before the body rejected the foreign head.

According to Canavero in his paper on human head transplants, the monkey lived eight days and was, by all measures, normal, having suffered no complications. However, Dr Jerry Silver who worked in the same lab as Dr White has more haunting memories. He toldCBS: I remember that the head would wake up, the facial expressions looked like terrible pain and confusion and anxiety in the animal. The head will stay alive, but not very long. It was just awful. I dont think it should ever be done again.

More recently, Chinese doctor Xiaoping Ren claims to have conducted head transplants on more than 1,000 mice. The Wall Street Journal reports to have witnessed a mouse with a new head moving, breathing, looking around and drinking. But, crucially, none of these mice have lived longer than a few minutes.

Still, Dr Rens studies continue, and the latest reports are said to be promising, offering a possible answer to the risk of severe blood loss (or brain ischemia) during transplantation. The experimental method that we have described can allow for long-term survival, and thus assessment of transplant rejection and central nervous system recovery, bringing us one step closer to AHBR in man, the researchers wrote.

Ren himself has not ruled out taking part in the first human head transplant operation, according to the Daily Mail. "A human head transplant will be a new frontier in science. Some people say it is the last frontier in medicine. It is a very sensitive and very controversial subject but if we can translate it to clinical practice, we can save a lot of lives," he said.

"Many people say a head transplant is not ethical. But what is the essence of a person? A person is the brain not the body. The body is just an organ," he added.

In January 2016, Canavero told New Scientist that a head transplant had been successfully completed on a monkey in China, although details were sparse. "The monkey fully survived the procedure without any neurological injury of whatever kind," he said, although the article notes that the monkey only kept alive for 20 hours after the surgery for "ethical reasons," limiting its use as a comparison somewhat.

In September 2016, Canavero revealeda further trial of the head transplant on dogs.New Scientisthas seen video footage of a dog appearing to walk three weeks after its spinal cord was severed, with Canavero claiming that the outcome is the result of the same techniques he plans to use on Spiridonov next year.

However, speaking to a number of scientists for their view on the new evidence, New Scientistcould find few sceptics converted. "These papers do not support moving forward in humans," said Jerry Silver a neuroscientist at Cape Western Reserve University in Ohio.

"The dog is a case report, and you cant learn very much from a single animal without controls. They claim they cut the cervical cord 90 per cent but theres no evidence of that in the paper, just some crude pictures," added Silver.

You could say so, though Canavero doesn't see it quite like that. In fact, controversially he sees it more as a failure of other types of medicine, telling Medical News Today, "It will be about curing incurable neurological disorders for which other treatments have failed big time, so gene therapy,stem cells- they all just came to nothing. We have failed despite billions of dollars being poured into this sort of research."

"So actually, head transplant or body transplant, whatever your angle is, is actually a failure of medicine. It is not a brilliant success, a brilliant advancement to medical science. When you just haven't tackled biology, you don't know how to treat genes, you don't really understand, and you really need to resort to a body transplant, it means that you've failed. So this must not be construed as a success of medical research," he added.

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The spinal cord is a rope of nerves relaying messages from the brain to every organ, muscle, and nerve ending in the body. The cells that make up the spinal cord arent a homogeneousmass, but rather a combination of dozens of specialized neurons, each with its own important role to play in guiding signals and impulses to the right destination.

This week, a team of California researchers announced the successful production of a lab-grown neuron that could help heal spinal cord injuries by reestablishing the connection between brain and muscle. In apaperpublished inProceedings of the National Academy of Sciences, researchers from the Gladstone Institutes and University of California campuses in San Francisco and Berkeley described how they grew human spinal cord neurons from stem cells and successfully introduced the lab-grown cells into the spines of healthy mice.

Todd McDevitt is a senior investigator at Gladstone and lead author of the study. He said that his team chose the targeted neuron, called a V2a interneuron, because it serves as a long relay cable between the neurons in the brain and the motor neurons that connect directly to muscle. V2a interneurons are, in fact, some of the longest cells in the body, able to extend their axon the nerve fibers that transmit electrical impulses across several vertebrae.

Its one cell stretching out up to 1,000 times longer than a normal human cell, said McDevitt. These outstretched neurons, as long as several centimeters, seem to play a critical role in relaying messages along the spinal cord. So if they are damaged in a traumatic injury, the brain-muscle connection may be severed, potentially leading to paralysis.

But if those critical V2a interneurons could be regenerated in an injured spine, the researchers wondered, perhaps the spinal cord could re-establish the connection and heal itself.

For the past three years, McDevitt and his team have been working to culture viable human V2a interneurons from pluripotent stem cells. The process, known as differentiation, attempts to replicate in the lab the natural development of neurons from undifferentiated stem cells in a human embryo.

Decades of research in developmental biology have provided clues to how genes in a developing embryo direct different proteins and other chemical factors to create all manner of specialized cells. The trouble is that most of the recipes for these chemical cocktails were derived from studying animal embryos.

Obviously, for good reasons, we dont do experiments on human embryos, McDevitt said. You have to take a leap of faith from the developmental biology knowledge we have from worms and flies and think about how we can apply that really important biological information to the human context.

RELATED:Brain Implant Helps 'Locked-In' ALS Woman Communicate

After experimenting with round after round of chemical combinations, the researchers landed on a process that can now produce a sizable batch of human V2a interneurons in a little over two weeks. The first step was to inject the cells into the spinal cords of healthy mice and see if the cells survived. They did even better.

Within two weeks, we saw a number of these cells extend their axons over long distances five millimeters reliably, but some even longer than that, McDevitt said, adding that the wiry cells are also making important connections. Even though theyre mice, we see these human cells that appear to be connecting to other neurons.

Does this mean were close to a human therapy using injections of healthy neurons to repair damaged spines? Not quite. Trials will first need to be run with injured mice before any human subjects can be tested. Plus, its entirely possible that V2a interneurons only fix very specific types of spinal injuries, or none at all. It might require the production of other spinal cord neurons, or a combination of several, to find the most effective treatment.

At the most basic level, this work shows that we can successfully introduce a new type of spinal neuron made from human pluripotent stem cells, McDevitt said. I see it as a step in whats probably going to be a much bigger effort by the field.

WATCH: Are We Close to Repairing Spinal Cord Injuries?

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It's based on experimental research that suggests stem cells extracted from the pulp of these teeth might someday regrow a lost adult tooth or offer other regenerative medicine benefits -- some potentially life-saving.

"So I'll try not to get emotional here, but my husband was diagnosed with acute myeloid leukemia in 2011," said Bassetto, of Naperville, Illinois, head of a sales team at a software company.

In 2012, her husband, James, had a stem cell transplant to restore his bone marrow and renew his blood.

"He was very fortunate. He was one of six kids, and his brother was a perfect match," she said. She noted that her two children, Madeline, 23, and Alex, 19, may not be so lucky if they develop health problems, since they have only each other; the chance of two siblings being a perfect stem cell match is only 25%.

Unfortunately, her husband's stem cell transplant was not successful. He developed graft-versus-host disease, where his brother's donated stem cells attacked his own cells, and he died shortly afterward.

However, she says, the transplant had given him a chance at a longer life.

Last year, when her son saw a dentist for wisdom tooth pain, a brochure for dental stem cell storage caught Bassetto's eye and struck a chord.

"I know stem cells have tremendous health benefits in fighting disease, and there's a lot ways they're used today," she said. "Had my husband had his own cells, potentially, his treatment could have been more successful."

Medical breakthroughs happen all the time, said Bassetto. "Who knows what potential there is 20 years, 40 years down the road, when my son is an adult or an aging adult?

"Almost like a life insurance policy, is how I viewed it," she said.

Some scientists see storing teeth as a worthwhile investment, but others say it's a dead end.

"Research is still mostly in the experimental (preclinical) phase," said Ben Scheven, senior lecturer in oral cell biology in the school of dentistry at the University of Birmingham. Still, he said, "dental stem cells may provide an advantageous cell therapy for repair and regeneration of tissues," someday becoming the basis for reconstructing bone tissue, retinas and even optic neurons.

Dr. Pamela Robey, chief of the craniofacial and skeletal diseases branch of the National Institute of Dental and Craniofacial Research, acknowledges the "promising" studies, but she has a different take on the importance of the cells.

"There are studies with dental pulp cells being used to treat neurological disorders and problems in the eye and other things," Robey said. The research is based on the idea that these cells "secrete factors that encourage local cells to begin the repair process."

"The problem is, these studies have really not been that rigorous," she said, adding that many have been done only in animals and so provide "slim" evidence of benefits. "The science needs a lot more work."

Robey would know. Her laboratory discovered dental stem cells in 2003.

"My fellows, Songtao Shi and Stan Gronthos, did the work in my lab," Robey said. "Songtao Shi is a dentist, and basically he observed that, when you get a cavity, you get what's called 'reparative dentin.' In other words, the tooth is trying to protect itself from that cavity, so it makes a little bit of dentin to kind of plug the hole, so to speak."

Dentin is the innermost hard layer of tooth that lies beneath the enamel. Underneath the dentin is a soft tissue known as pulp, which contains the nerve tissue and blood supply.

Observing dentin perform reparative work, Shi hypothesized that this must mean there's a stem cell within the tooth that's able to activate and make dentin. So if you wanted to grow an adult tooth instead of getting an implant, knowing how to make dentin would be the start of the process, explained Robey.

Pursuing this idea, Shi, Gronthos and the team conducted their first study with wisdom teeth. They discovered that pulp cells in these third molars did indeed make dentin, but the cells found in baby teeth, called SHED (stem cells from human exfoliated deciduous teeth), had slightly different properties.

"The SHED cells seem to make not only dentin but also something that is similar to bone," Robey said. This "dentin osteogenic material" is a little like bone and a little like dentin -- "unusual stuff," she said.

There is a meticulous process for extracting stem cells from the pulp.

"We very carefully remove any soft tissue that's adhering to the tooth. We treat it with disinfectant, because the mouth is not really that clean," Robey said, laughing.

Scientists then use a dental drill to pass the enamel and dentin -- "kind of like opening up a clam," said Robey -- to get to the pulp. "We take the pulp out, and we digest it with an enzyme to release the cells from the matrix of the pulp, and then we put the cells into culture and grow them."

According to Laning, even very small amounts of dental pulp are capable of producing many hundreds of millions of structural stem cells.

Harvesting dental stem cells is not a matter of waiting for the tooth to fall out and then quickly calling your dentist. When a baby tooth falls out, the viability of the pulp is limited if it's not preserved in the proper solution.

American Academy of Pediatric Dentistry President Dr. Jade Miller explained that "it's critical that the nerve tissue in that pulp tissue, the nerve supply and blood supply, still remain intact and alive." Typically, the best baby teeth to harvest are the upper front six or lower front six -- incisors and cuspids, he said.

For a child between 5 and 8 years of age, it's best to extract the tooth when there's about one-third of the root remaining, Miller said: "It really requires some planning, and so parents need to make this decision early on and be prepared and speak with their pediatric dentist about that."

Bassetto found the process easy. All it involved was a phone call to the company recommended by her dentist.

"They offer a service where they grow the cells and save those and also keep the pulp of the tooth without growing cells from it," she said. "I opted for both." From there, she said, the dentist shipped the extracted teeth overnight in a special package.

Bassetto said she paid less than $2,000 upfront, and now $10 a month for continued storage.

So is banking teeth something parents should be doing?

In a policy statement, the American Academy of Pediatric Dentistry "encourages dentists to follow future evidence-based literature in order to educate parents about the collection, storage, viability, and use of dental stem cells with respect to autologous regenerative therapies."

"Right now, I don't think it is a logical thing to do. That's my personal opinion," said Robey of the National Institute of Dental and Craniofacial Research. As of today, "we don't have methods for creating a viable tooth. I think they're coming down the pike, but it's not around the corner."

Science also does not yet support using dental pulp stem cells for other purposes.

"That's not to say that in the future, somebody could come up with a method that would make them very beneficial," Robey said.

Still, she observed, if science made it possible to grow natural teeth from stem cells and you were in a car accident, for example, and lost your two front teeth, you'd probably be "very happy to give up a third molar to use the cells in the molar to create new teeth." Third molars are fairly expendable, she said.

Plus, Robey explained, it may not be necessary to bank teeth: Another type of stem cell, known as induced pluripotent stem cells, can be programmed into almost any cell type.

"It's quite a different story than banking umbilical cord blood, which we do know contains stem cells that re-create blood," Robey said.

"So cord blood banking -- and now we have a national cord blood bank as opposed to private clinics -- so there's a real rationale for banking cord blood, whereas the rationale for banking baby teeth is far less clear," Robey said.

And there's no guarantee that your long-cryopreserved teeth or cells will be viable in the future. Banking teeth requires proper care and oversight on the part of cryopreservation companies, she said. "I think that that's a big question mark. If you wanted to get your baby teeth back, how would they handle that? How would they take the tooth out of storage and isolate viable cells?"

Provia's Laning, who has "successfully thawed cells that have been frozen for more than 30 years," dismissed such ideas.

"Cryopreservation technology is not the problem here," he said. "Stem cells from bone marrow and other sources have been frozen for future clinical use in transplants for more than 50 years. Similarly, cord blood has a track record of almost 40 years." The technology for long-term cryopreservation has been refined over the years without any substantial changes, he said.

Despite issues and doubts, Miller, of the pediatric dentistry academy, said parents still need to consider banking baby teeth.

A grandparent, he is making the decision for his own family.

"It's really at its infancy, much of this research," he said. "There's a very strong chance there's going to be utilization for these stem cells, and they could be life-saving."

He believes that saving baby teeth could benefit not only his grandchildren but also their older siblings and various other family members if their health goes awry and a stem cell treatment is needed.

"The science is strong enough to show it's not science fiction," Miller said. "There's going to be a significant application, and I want to give my grandkids the opportunity to have those options."

Aside from cost, Miller said there are other considerations: "Is this company going to be around in 30, 40 years?" he asked. "That's not an easy thing to figure out."

Having taken the leap, Bassetto doesn't worry.

"In terms of viability, you know, if something were to happen with the company, you could always get what's stored and move it elsewhere, so I felt I was protected that way," she said. She feels "pretty confident" with her decision and plans to store her grandchildren's baby teeth.

Still, she concedes that her circumstances may be rare.

"Not everybody's going to be touched by some kind of disease where it just hits home," Bassetto said. "For me, that made it a no-brainer."

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A bone marrow drive for James Christopher Allums, 21, and his sister Elizabeth, 3, is Monday, May 1 at locations throughout northeast Louisiana.

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The News Star 11:33 a.m. CT April 26, 2017

University of Louisiana Monroe(Photo: Courtesy image)

A bone marrow drive for James Christopher Allums, 21, and his sister Elizabeth, 3, is Monday, May 1 at locations throughout northeast Louisiana.

University of Louisiana Monroe Medical Laboratory Science faculty and students are helping organize the drive. The drive on campus is 9 a.m.-5 p.m. in the SUB and Quad.

May 1 is National Fanconi Anemia Day. James Christopher and Elizabeth suffer from this disease, which is fatal without a bone marrow or stem cell transplant. They are the children of Chris and Ellen Allums.

Melanie Chapman, assistant professor to the School of Health Professions, said, "This is a wonderful opportunity for ULM Warhawks to fly high by working together and setting aside our busy agendas to give two great kids, and possibly others, the chance to live out their years. I am privileged to be a part of ULM and this community effort."

Bone marrow drive locations:

Times vary and new locations may be added. For information, check Facebook The Friends of James Christopher and Elizabeth Allums or visit caringbridge.org and search James Christopher Allums .

MORE NEWS;The Fabulous Equinox Orchestra takes the stage at ULM Friday

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It was Thursday afternoon, and the little girl from near Cologne, Germany, and the 40-year-old Duluth woman had known each other for less than 24 hours. But it was obvious that Edwards already had bonded with Ina and her little sister Mila.

They were together because the girls' mother had given Edwards a much greater gift: the gift of life.

"By your donation, I still get to be a mom," Edwards told Daniela Halfkann, 30. "(You're) a mom, so you completely understand how important it is to be here with your children."

Edwards, the mother of 15-year-old twin boys and the wife of Duluth Fire Chief Dennis Edwards, is alive because of the stem cell transplant she received at the Mayo Clinic on Oct. 31, 2014. As a result, she said, she is in remission from the rare and aggressive form of leukemia with which she had been diagnosed that June.

All she was told at the time of the transplant was that the donor was a woman from Germany.

Halfkann had registered as a potential stem cell or bone marrow donor at the large insurance company where she works in Cologne, she said. One day she received a call, saying her donation was needed.

After the six-hour procedure, Halfkann was told nothing more than that the recipient was a woman in the United States.

After a two-year waiting period required in Germany, the two women learned each other's identities last October and connected via Facebook.

Their meeting in Duluth was arranged by Amanda Schamper, Midwest donor recruitment coordinator for DKMS, the Germany-based organization that facilitated the donation.

Halfkann made the trip along with husband Stefan and their daughters, leaving their home at 3 a.m. on Tuesday and arriving at the Duluth International Airport at 5 p.m. on Wednesday.

Like Edwards, DKMS wants to raise awareness of the need for people to enter the registry, said Schamper, who also traveled to Duluth for the occasion.

She said 14,000 patients are in need of a peripheral blood stem cell or bone marrow donation, but fewer than half will get one because there's no match on the registry.

"We're looking for a particular protein in our DNA," she explained.

Only in 30 percent of cases are siblings a match. Edwards' brother and sister both had been screened, she said, and neither was a match for her.

Finding a match "is equated to finding your genetic twin, or winning the genetic lottery," Schamper said.

If more people were on the registry a process that only requires taking a swab from your cheek there would be more potential matches. But only 2 percent of eligible Americans are registered, Schamper said.

When the Halfkanns arrived at the gate on Wednesday, Dennis and Merissa Edwards, along with sons Caden and Jaxon, were waiting at the gate.

It was an emotional moment.

"It was hard for me," Merissa Edwards said on Friday, speaking to Daniela Halfkann. "I was crying. I was so emotional, so happy to meet you and hug you."

She wiped away a tear. "I still am."

"It was amazing," Halfkann responded. "I cried at the gate, too."

The Halfkanns, who are staying at the Edgewater, initially focused on recovery from jet lag. But Edwards is making sure they'll get a full taste of Duluth and Minnesota before beginning their return trip to Germany next Saturday. That includes visits to the Mall of America, the Great Lakes Aquarium and a trip up the North Shore.

A "thank-you party," open to the public, is planned on Sunday afternoon. Halfkann also will be recognized on Monday during the Saints Sports Awards ceremony at the College of St. Scholastica, where Edwards is an administrative assistant in the athletics department.

Recovery from the ravages of leukemia has been a long process, Edwards said, but she remains in remission. She gets a PET scan every six months to make sure that's still the case; the next one takes place next week.

Edwards shares her story, she said, not to call attention to herself but to highlight the need for people to take the simple step of registering as a potential donor.

"It's so important for us to help other people keep their families together and save a mother or father or son or daughter," she said. "The more people we can encourage to cheek-swab and get on the registry, the more lives we can help save and help families stay together."

TO LEARN MORE

For more information and to learn how to get on the bone marrow and peripheral blood stem cell registry, visit dkms.org.

IF YOU GO

The thank-you party for Daniela Halfkann will be from 2 to 5 p.m. on Sunday at The Other Place Bar and Grill, 3930 E. Calvary Road.

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Tummy tucks really hurt. Doctors carve from hip to hip, slicing off skin, tightening muscles, tugging at innards. Patients often need strong painkillers for days or even weeks, but Mary Hernandez went home on just over-the-counter ibuprofen.

The reason may be the yellowish goo smeared on her 18-inch wound as she lay on the operating table. The Houston woman was helping test a novel medicine aimed at avoiding opioids, potent pain relievers fueling an epidemic of overuse and addiction.

Vicodin, OxyContin and similar drugs are widely used for bad backs, severe arthritis, damaged nerves and other woes. They work powerfully in brain areas that control pleasure and pain, but the body adapts to them quickly, so people need higher and higher doses to get relief.

This growing dependence on opioids has mushroomed into a national health crisis, ripping apart communities and straining police and health departments. Every day, an overdose of prescription opioids or heroin kills 91 people, and legions more are brought back from the brink of death. With about

2 million Americans hooked on these pills, evidence is growing that theyre not as good a choice for treating chronic pain as once thought.

Drug companies are working on alternatives, but have had little success.

Twenty or so years ago, they invested heavily and failed miserably, said Dr. Nora Volkow, director of the National Institute on Drug Abuse.

Pain is a pain to research. Some people bear more than others, and success cant be measured as objectively as it can be with medicines that shrink a tumor or clear an infection. Some new pain drugs that worked well were doomed by side effects Vioxx, for instance, helped arthritis but hurt hearts.

Some fresh approaches are giving hope:

Bespoke drugs, as Volkow calls them. These target specific pathways and types of pain rather than acting broadly in the brain. One is Enbrel, which treats a key feature of rheumatoid arthritis and, in the process, eases pain.

Drugs to prevent the need for opioids. One that Hernandez was helping test numbs a wound for a few days and curbs inflammation. If people dont have big pain after surgery, their nerves dont go on high alert and theres less chance of developing chronic pain that might require opioids.

Funky new sources for medicines. In testing: Drugs from silk, hot chili peppers and the venom of snakes, snails and other critters.

Novel uses for existing drugs. Some seizure and depression medicines, for example, can help some types of pain.

The biggest need, however, is for completely new medicines that can be used by lots of people for lots of problems. These also pose the most risk for companies and patients alike.

ONE DRUGS BUMPY ROAD

In the early 2000s, a small biotech company had a big idea: blocking nerve growth factor, a protein made in response to pain.

The companys drug, now called tanezumab, works on outlying nerves, helping to keep pain signals from muscles, skin and organs from reaching the spinal cord and brain good for treating arthritis and bad backs.

Pfizer Inc. bought the firm in 2006 and expanded testing. But in 2010, some people on tanezumab and similar drugs being tested by rivals needed joint replacements. Besides dulling pain, nerve growth factor may affect joint repair and regeneration, so a possible safety issue needed full investigation in a medicine that would be the first of its type ever sold, said one independent expert, Dr. Jianguo Cheng, a Cleveland Clinic pain specialist and science chief for the American Academy of Pain Medicine.

Regulators put some of the studies on hold. Suddenly, some people who had been doing well on tanezumab lost access to it. Phyllis Leis in Waterfall, a small town in south-central Pennsylvania, was one.

I was so angry, she said. That was like a miracle drug. It really was. Unless you have arthritis in your knees and have trouble walking, youll never understand how much relief and what a godsend it was.

Her doctor, Alan Kivitz of Altoona Center for Clinical Research, has helped run hundreds of pain studies and consults for Pfizer and many other companies.

You rarely get people to feel that good as many of them did on the nerve growth factor drugs, he said.

A drug with that much early promise is unusual, said Ken Verburg, who has led Pfizers pain research for several decades.

When you do see one, you fight hard to try to bring one to the market, he said.

An independent review ultimately tied just a few serious joint problems to tanezumab and the suspension on testing was lifted in August 2012. But a new issue nervous system effects in some animal studies prompted a second hold later that year, and that wasnt lifted until 2015.

Now Eli Lilly & Co. has joined Pfizer in testing tanezumab in late-stage studies with 7,000 patients.

Results are expected late next year about 17 years after the drugs conception.

AVOIDING PAIN AND DRUGS

What if a drug could keep people from needing long-term pain relief in the first place? Heron Therapeutics Inc. is testing a novel, long-acting version of two drugs the anesthetic bupivacaine and the anti-inflammatory meloxicam for notoriously painful operations like tummy tucks, bunion removal and hernia repair.

Company studies suggest it can numb wounds for about three days and cut patients need for opioids by 30 to 50 percent.

Theres a good chance of preventing brain responses that lead to chronic pain if patients can get through that initially very rough period, said Dr. Harold Minkowitz, a Houston anesthesiologist who consults for Heron and treated Hernandez in the tummy tuck study.

Hernandez was part of an experiment testing the drug versus a placebo and doesnt know whether she got the drug or a dummy medicine. But she hurt less than she expected to and never filled a prescription for pain pills.

The goal would be to have half or more of patients not requiring an opiate after they go home, said Herons chief executive, Barry Quart. You have far fewer opiates going out into society, far fewer opiates sitting in medicine cabinets that make their way to a high school.

Studies so far are mid-stage too small to prove safety and effectiveness but Heron plans more aimed at winning approval.

ON THE HORIZON

Many companies have their eyes on sodium channel blockers, which affect how nerves talk to each other and thus might help various types of pain. Others are testing cell therapies for nerve pain. Stem cells can modulate immune responses and inflammation, and may overcome a raft of problems, said Cheng of the pain medicine academy.

Some companies, including Samumed, Centrexion Therapeutics and Flexion Therapeutics, are testing long-acting medicines to inject in knees to relieve arthritis pain. Samumeds aims to regenerate cartilage.

And then theres marijuana. A cannabis extract is sold as a mouth spray in Britain for nerve pain and other problems from multiple sclerosis. But cannabinoid research in the U.S. has been hampered by marijuanas legal status. A special license is needed and most researchers dont even try to obtain one, said Susan Ingram, a neurosurgery scientist at Oregon Health & Science University.

She is studying cannabinoid receptors in the brain, looking at how pain affects one type but not another. Such work might someday lead to drugs that relieve pain but dont produce a high or addiction.

Selective activity has precedent: The drug buprenorphine partially binds to opioid receptors in the brain and has become an extraordinarily successful medication for treating addiction, said Volkow, of the national drug institute.

It has shown pharmaceutical companies that if you come up with a good intervention, there is an opportunity to recover their costs, she said.

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In an autologous BMT procedure, the healthy stem cells from the patient are taken out and preserved

IANS | New Delhi April 21, 2017 Last Updated at 05:00 IST

A team of doctors in New Delhi has successfully treated a 24-year-old girl suffering from Multiple Sclerosis (MS) with bone marrow transplant (BMT).

Kanika Juneja was diagnosed with MS an autoimmune disorder where the body's immune system starts attacking the protective sheet covering the nerve cells in the brain and the spinal cord.

She went through several rounds of treatments but could not be cured. Juneja got another chance at life at Fortis Healthcare where the doctors treated her with BMT.

"In an autologous BMT procedure, the healthy stem cells from the patient are taken out and preserved. Chemotherapy is then administered to reset the body's immunity and then the stem cells are injected back to rescue the person from the side effects of chemotherapy. After the surgery, the patient is kept under isolation for a few months to ensure he/she does not contract any infection," explained Dr Rahul Bhargava, Director, Clinical Hematology and Bone Marrow Transplant, Fortis Memorial Research Institute (FMRI).

Since conventional steroid injections and immune therapy are expensive and don't promise a cure, Bhargava thought of going for a BMT for Juneja.

Juneja is now actively involved in raising awareness about MS amongst the community through social media.

"I had just completed my college education when I was diagnosed with multiple sclerosis. I was lucky because I got diagnosed within a week of my symptoms and could avail treatment options faster," Juneja said.

"In this case, we have proved that bone marrow transplant can be seen as a successful alternate treatment option for multiple sclerosis patients, giving them a fresh shot at life," added Dr Simmardeep Singh Gill, Zonal Director, FMRI, in a statement.

Currently, there are 2.3 million people living with multiple sclerosis worldwide.

A team of doctors in New Delhi has successfully treated a 24-year-old girl suffering from Multiple Sclerosis (MS) with bone marrow transplant (BMT).

Kanika Juneja was diagnosed with MS an autoimmune disorder where the body's immune system starts attacking the protective sheet covering the nerve cells in the brain and the spinal cord.

She went through several rounds of treatments but could not be cured. Juneja got another chance at life at Fortis Healthcare where the doctors treated her with BMT.

"In an autologous BMT procedure, the healthy stem cells from the patient are taken out and preserved. Chemotherapy is then administered to reset the body's immunity and then the stem cells are injected back to rescue the person from the side effects of chemotherapy. After the surgery, the patient is kept under isolation for a few months to ensure he/she does not contract any infection," explained Dr Rahul Bhargava, Director, Clinical Hematology and Bone Marrow Transplant, Fortis Memorial Research Institute (FMRI).

Since conventional steroid injections and immune therapy are expensive and don't promise a cure, Bhargava thought of going for a BMT for Juneja.

Juneja is now actively involved in raising awareness about MS amongst the community through social media.

"I had just completed my college education when I was diagnosed with multiple sclerosis. I was lucky because I got diagnosed within a week of my symptoms and could avail treatment options faster," Juneja said.

"In this case, we have proved that bone marrow transplant can be seen as a successful alternate treatment option for multiple sclerosis patients, giving them a fresh shot at life," added Dr Simmardeep Singh Gill, Zonal Director, FMRI, in a statement.

Currently, there are 2.3 million people living with multiple sclerosis worldwide.

IANS

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A team of biomedical engineering researchers has created a revolutionary 3D-bioprinted patch that can help heal scarred heart tissue after a heart attack. Two of the researchers involved are biomedical engineering Associate Professor Brenda Ogle (right) and Ph.D. student Molly Kupfer (left). Credit: Patrick OLeary, University of Minnesota

A team of biomedical engineering researchers, led by the University of Minnesota, has created a revolutionary 3D-bioprinted patch that can help heal scarred heart tissue after a heart attack. The discovery is a major step forward in treating patients with tissue damage after a heart attack.

See Also:How 3D Printing Could Revolutionise Organ Transplantation

According to the American Heart Association, heart disease is the No. 1 cause of death in the U.S. killing more than 360,000 people a year. During a heart attack, a person loses blood flow to the heart muscle and that causes cells to die. Our bodies cant replace those heart muscle cells so the body forms scar tissue in that area of the heart, which puts the person at risk for compromised heart function and future heart failure.

In this study, researchers from the University of Minnesota-Twin Cities, University of Wisconsin-Madison, and University of Alabama-Birmingham used laser-based 3D-bioprinting techniques to incorporate stem cells derived from adult human heart cells on a matrix that began to grow and beat synchronously in a dish in the lab.

Watch a video of the cells beating on the patch.

When the cell patch was placed on a mouse following a simulated heart attack, the researchers saw significant increase in functional capacity after just four weeks. Since the patch was made from cells and structural proteins native to the heart, it became part of the heart and absorbed into the body, requiring no further surgeries.

This is a significant step forward in treating the No. 1 cause of death in the U.S., said Brenda Ogle, an associate professor of biomedical engineering at the University of Minnesota. We feel that we could scale this up to repair hearts of larger animals and possibly even humans within the next several years.

Related:Synthetic Cardiac Stem Cells Developed

Ogle said that this research is different from previous research in that the patch is modeled after a digital, three-dimensional scan of the structural proteins of native heart tissue. The digital model is made into a physical structure by 3D printing with proteins native to the heart and further integrating cardiac cell types derived from stem cells. Only with 3D printing of this type can we achieve one micron resolution needed to mimic structures of native heart tissue.

We were quite surprised by how well it worked given the complexity of the heart, Ogle said. We were encouraged to see that the cells had aligned in the scaffold and showed a continuous wave of electrical signal that moved across the patch.

Ogle said they are already beginning the next step to develop a larger patch that they would test on a pig heart, which is similar in size to a human heart.

The research was funded by the National Science Foundation, National Institutes of Health, University of Minnesota Lillehei Heart Institute, and University of Minnesota Institute for Engineering in Medicine.

This article has been republished frommaterialsprovided by University of Minnesota. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference:

Gao, L., Kupfer, M. E., Jung, J. P., Yang, L., Zhang, P., Sie, Y. D., . . . Zhang, J. (2017). Myocardial Tissue Engineering With Cells Derived From Human-Induced Pluripotent Stem Cells and a Native-Like, High-Resolution, 3-Dimensionally Printed ScaffoldNovelty and Significance. Circulation Research, 120(8), 1318-1325. doi:10.1161/circresaha.116.310277

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3D-printed Patch Can Help Mend a 'Broken' Heart | Technology ... - Technology Networks

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The New Cellogica Website Features In-Depth Information about the Skin Care Product, which Includes Stem Cell Technology

LOS ANGELES, CA / ACCESSWIRE / April 20, 2017 / The founders of Cellogica, a top line of skincare products that utilize stem cells and other innovative ingredients, are pleased to announce the re-launch of their website, Cellogica.com.

To check out the recently revised website, which is now easier than ever to navigate and features updated information about Cellogica, please visit http://www.cellogica.com at any time.

As a company spokesperson noted, Cellogica's "Two Secrets of Youth" involve the use of stem cell technology and also its MAC-5 Complex, which includes five ingredients that may help the skin look as young as possible. Rather than merely repairing the skin, Cellogica may actually help stop the loss of existing skin stem cells, as well as prevent premature aging.

Cellogica features a day cream, a non-greasy and light product which is designed to protect and enhance the skin and provide it with a natural barrier to the damaging UV rays of the sun and harsh weather. It also includes a night cream that works as the user sleeps by naturally repairing, restoring and regenerating the skin.

As the spokesperson noted, because skin stem cells are responsible for regenerating new and healthy skin cells, the founders of Cellogica were inspired to create a skin care cream that contains stem cells.

"Our revolutionary Stem Cell Technology is derived from strains of rare Swiss apples (Malus Domestica) and the Alpine Rose (Rhododentron Ferrugineum)," the spokesperson said, adding that together, these two very powerful stem cell extracts may allow for the regeneration of new skin stem cells, prevent the loss of existing skin stem cells, and increase the skin's barrier function.

"They may protect and repair the skin and combat against chronological aging, thus leading to fresh, healthy and vibrant looking skin."

The MAC-5 Complex is the other key component to Cellogica's ability to help improve the appearance of the skin. The proprietary combination includes Syn-Coll, which is an aqueous unpreserved glycerin-based solution that was developed to reduce wrinkles, as well as stimulate collagen synthesis. The other four ingredients in the MAC-5 Complex are RonaFlair LDP, hyaluronic acid, Syn-Ake, and Kojic acid, which may help eliminate blotchy skin while evening out the skin tone.

About Cellogica:

Cellogica is a premiere skincare line utilizing newly discovered stem cells to stop and reverse the physical signs of aging. To learn more about the product, please visit their website, http://www.cellogica.com.

Contact:

Darryl Burke admin@rocketfactor.com (949) 555-2861

SOURCE: Power Americas Minerals Corp.

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Plasticell, a developer of cell therapies including hematopoietic cell replacement therapies, recently announced it has partnered with Kings College London to progress preclinical trials of its artificial blood platelet product, manufactured from pluripotent stem cells. The work is supported by a MedCity research grant which funds collaboration between leading SMEs and academics from London universities.

Over 10 million units of platelets are transfused worldwide each year in one of the most common procedures in clinical medicine. However, platelets derived from human donors can transmit infections and trigger serious immune reactions that eventually render the therapy ineffective (a condition known as alloimmune refractoriness). In addition, since platelet donations require pathogen testing and cannot be frozen for later use, supply shortages can occur under certain circumstances.

Plasticell has developed robust, cost-effective methods of producing functional platelets from human induced pluripotent stem cells (iPSCs) and has scaled these up to intermediate bioreactor level, allowing manufacture of product for pre-clinical studies. Kings College will contribute world-leading expertise and in vivo models to characterise the dynamics, lifespan, safety and efficacy of transfused platelets.

In addition to providing a more stable and safe supply of universal platelets, the use of iPS cells would allow us to create immunologically compatible matched platelets for patients suffering from alloimmune refractoriness, commented Dr Marina Tarunina, Principal Scientist leading the project at Plasticell.

The project is part of Plasticells hematopoietic cell therapy portfolio, which includes the expansion of umbilical cord- and bone- derived hematopoietic stem cells, and the manufacture of various blood cell types. Plasticell recently announced it had received Innovate UK funding for a 1.1M project to manufacture red blood cells from pluripotent stem cells, in collaboration with the University of Edinburgh.

About Plasticell Plasticell is a biotechnology company leading the use of high throughput technologies to develop stem cell therapies. The Companys therapeutic focus is in hematopoietic stem cell therapy, anaemia and thrombocytopenia, cancer immunotherapy and diabetes/obesity. Plasticells Combinatorial Cell Culture (CombiCult) platform technology, allows it to test very large numbers of cell culture variables in combinations to discover optimal laboratory protocols for the manipulation of stem cells and other cell cultures and has received a number of industry awards including the Queens Award for Enterprise in Innovation and the R&D 100 Award. For more information, visit http://www.plasticell.co.uk.

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IPS Cell Therapy Comments Off on Plasticell And Kings College London To Collaborate In Trials Of Blood Platelet Substitute – Clinical Leader | April 20th, 2017

SINGAPORE - It was a bone marrow match that defied the odds of one in 20,000 - not once, but twice.

Just months after his first match fell through when the patient withdrew from treatment, Mr Phil Tan, 27, was again identified as a suitable bone marrow donor for another patient.

His donation saved the life of eight-year-old Ryssa, who was diagnosed with a rare blood disease called Myelodysplastic Syndrome about three years ago. Both met for the first time on Wednesday (April 19). Ryssa received the transplant just before her seventh birthday.

Mr Tan was one of 22 Singaporeans who were honoured by Minister for Home Affairs and Law K. Shanmugam for saving the life of a patient through the donation of their bone marrow.

"We celebrate those who have come forward without expecting a benefit, other than making a huge difference in someone else's life. It is the real spirit of giving," said Mr Shanmugam, who is a patron of the Bone Marrow Donor Programme (BMDP).

Bone marrow or blood stem cell transplant is the best treatment option for patients diagnosed with blood diseases such as leukaemia and lymphoma.

At any one time, there are at least 50 patients waiting to find a matching donor.

Siblings of the patient are the first options for a donation, as they have a one in four chance of DNA compatibility for a transplant.

When that fails, the next option would be a match with a volunteer donor registered in the BMDP.

To date, more than 75,000 volunteers have joined the BMDP register, which records the genetic type of each person.

Since 2015, more than 50 Singaporeans have donated their bone marrow to patients in Singapore and overseas, including in the United States, Britain, Canada and France.

The BMDP, which was set up in 1993, aims to increase the size of the local donor register by another 50,000 by next year.

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8-year-old patient surprises her bone marrow donor at their first ... - The Straits Times

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A team of researchers in Japan has combined simple agarose with advanced machine learning techniques to study the differentiation of stem cells.

Asian Scientist Newsroom | April 20, 2017 | In the Lab

AsianScientist (Apr. 20, 2017) - Stem cell differentiation can now be seen thanks to a combination of machine learning and microfabrication techniques developed by scientists at the RIKEN Quantitative Biology Center in Japan. The results, published in PLOS ONE, followed the differentiation of human mesenchymal stem cells (MSC) which are easily obtained from adult bone marrow.

MSCs have proven to be important for regenerative medicine and stem cell therapy because they can potentially repair many different types of organ damage. Depending on the way the cells are grown, the results can be quite different, making controlling differentiation is an important goal.

Observing MSC differentiation under different conditions is an essential step in understanding how to control the process. However, this has proved challenging on two fronts. First, the physical space in which the cells are grown has a dramatic impact on the results, causing significant variation in the types of cells into which they differentiate. Studying this effect requires consistent and long lasting spatial confinement. Second, classifying the cell types which have developed through manual observation is time consuming.

Previous studies have confined cell growth with fibronectin on a glass slide. The cells can only adhere and differentiate where the fibronectin is present and are thus chemically confined. However, this procedure requires high technical skill to maintain the confinement for an extended period of time. To overcome this, the first author of the study, Dr. Nobuyuki Tanaka, decided to look for a new way to confine them. Using a simple agarose gel physical confinement system, he found that he could maintain them for up to 15 days.

It was wonderful to be able to do this, because agarose gel is a commonly used material in biology laboratories and can be easily formed into a micro-cast in a PDMS silicone mold, Tanaka said.

The advantage of this system is that once the PDMS molds are obtained the user only needs agarose gel and a vacuum desiccator to create highly reproducible micro-casts.

Tanaka's paper also describes an automated cell type classification system, using machine learning, which reduces the time and labor needed to analyze cells.

Combined together, these tools give us a powerful way to understand how stem cells differentiate in given conditions, he added.

The article can be found at: Tanaka et al. (2017) Simple Agarose Micro-confinement Array and Machine-learning-based Classification for Analyzing the Patterned Differentiation of Mesenchymal Stem Cells.

Source: RIKEN; Photo: Shutterstock. Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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Automatically Observing Stem Cell Differentiation - Asian Scientist Magazine

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A female specimen of a zebrafish (Danio rerio) breed with fantails

Cardiovascular disease is one of the leading causes of death in the world with approximately 30% of global mortality attributed to it.Cardiovascular disease conditions lead to damage of cardiac muscle cells resulting in defective heart function.

Stem cell therapy, though a relatively young science, is one of the upcoming treatment options for such diseases in the near future. In principle, stem cells from embryos can be made to differentiate into many functional cell types including heart cells, which can be effectively used to replace damaged cells in heart patients. To achieve this, scientists are constantly trying to understand the developmental process by which the heart is formed from various progenitors in a growing embryo. Once we understand this pathway at an organismal level, efforts can be made to use these stem cells for regenerative medicine.

A team of scientists led by Bruno Reversade from Singapore and Ian Scott from the University of Toronto have come together to study heart development in the Zebrafish model.

Zebrafish, scientifically called Danio rerio, is one of the powerful models for studying various organ functions. Although there are major structural differences between zebrafish and humans, there are strong similarities at the genetic and morphological levels. One of the biggest advantages of using zebrafish is that unlike mice, rats or monkeys, zebrafish embryos are transparent and hence provide a tractable system for visualizing these important developmental processes in situ.

During embryonic development, early heart development requires the activation of one of the important signaling pathways called Nodal or TGF pathway. Depending on the activation levels of Nodal, different cells become different stem cell types. Hence, there has to be a mechanism for fine-tuning of this signaling to produce these activity thresholds. Scientists from these two groups have recently identified the candidates involved in this fine-tuning.

Researchers recently identified a mutation, which leads to zebrafish with no heart at all. This suggests that this mutation somehow alters an early developmental process in heart formation. Interestingly, this gene encodes for a protein called Apelin receptor. So how does the Apelin receptor affect heart development? Scientists revealed that mutation in this receptor caused lower levels of Nodal signaling in mutant embryos as compared to the normal ones, thus failing to induce the formation of cardiac stem cells. When Nodal activity is artificially elevated in embryos that lack the Apelin receptor, they were able to develop hearts further confirming the role of Apelin receptor in this pathway.

A detailed understanding of this molecular cross-talk could help in the derivation of specific cell types from human embryonic stem cells for regenerative medicine, says Bruno Reversade, a human geneticist at the A*STAR Institute of Medical Biology, who co-led the investigation.

Further, this collaborative study showed that the Apelin receptor does not work in cells that produce or receive Nodal signals, suggesting that the Apelin receptor modulates Nodal signaling levels by acting in cells that lie between the cells that release Nodal signals and the cardiac progenitors.

In brief, this receptor functions as a distant regulator for fine-tuning the expression of the Nodal pathway during early stages of heart development ensuring proper cardiac development. One important area of future study is to determine whether modulating the levels of this receptor can prove useful for patients with various heart disorders.

Original article can be found here: https://elifesciences.org/content/5/e13758

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Scientists identify mechanisms of early heart development in Zebrafish - Biotechin.Asia

Cardiac Stem Cells Comments Off on Scientists identify mechanisms of early heart development in Zebrafish – Biotechin.Asia | April 18th, 2017