SBP Scientist Receives Prestigious WM Keck Foundation Grant – Newswise (press release)

Newswise La Jolla, Calif., July 10, 2017 Sanford Burnham Prebys Medical Discovery Institute (SBP) is pleased to announce that the W.M. Keck Foundation has awarded a $1M grant to Duc Dong, Ph.D., to advance research to generate replacement organs and cellssuch as insulin producing cells for diabetes or dopamine-producing neurons for Parkinsons diseasedirectly in the body and without the use of stem cells.

The grant will allow Dong to extend his studies reprogramming dispensable cells such as skin, vasculature and fat cells while they remain in the body, in vivo, without the use of cultures or induced pluripotent stem cell techniques, which could be a safer and more effective method to treat degenerative diseases and injuries.

Dong, an assistant professor in the Human Genetics Program, uses zebrafishtiny striped fish commonly used for genetic studies-as a vertebrate model to reprogram cells into unrelated types, completely within the body of these living animals. Dongs research team already has proof-of-concept data demonstrating in vivo conversion of muscle and skin cells into beta-cell precursors (the cells that mature to produce insulin)an accomplishment assumed to be impossible by most scientists.

Im honored to have received this grant from the Foundation, says Dong. The award will support my vision to ultimately make in vivo cell lineage reprogramming a practical therapeutic strategy to replace or even enhance lost, damaged or aging tissues. Our next steps are to develop technologies to convert any cells in the body, at any age, into any cell type of interest, and to uncover the molecular mechanisms driving that process.

Based in Los Angeles, the W. M. Keck Foundation was established in 1954 by the late W. M. Keck, founder of the Superior Oil Company. The Foundations grant making is focused primarily on pioneering efforts in the areas of medical research, science and engineering and undergraduate education. The Foundation also maintains a Southern California Grant Program thatprovides support for the Los Angeles community, with a special emphasis on children and youth. For more information, please visit http://www.wmkeck.org.

About SBPSanford Burnham Prebys Medical Discovery Institute (SBP) is an independent nonprofit medical research organization that conducts world-class, collaborative, biological research and translates its discoveries for the benefit of patients. SBP focuses its research on cancer, immunity, neurodegeneration, metabolic disorders and rare childrens diseases. The Institute invests in talent, technology and partnerships to accelerate the translation of laboratory discoveries that will have the greatest impact on patients. Recognized for its world-class NCI-designated Cancer Center and the Conrad Prebys Center for Chemical Genomics, SBP employs about 1,100 scientists and staff in San Diego (La Jolla), Calif., and Orlando (Lake Nona), Fla. For more information, visit us at SBPdiscovery.org or on Facebook at facebook.com/SBPdiscovery and on Twitter @SBPdiscovery.

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SBP Scientist Receives Prestigious WM Keck Foundation Grant - Newswise (press release)

Research on Stem Cell Therapy | Liveyon Regenerative Medicine

Liveyon LLC is the exclusive worldwide distributor of a regenerative medicine product that is derived from umbilical cord. This product contains cells, stem cells and growth factors which may serve as a therapy for various degenerative diseases/disorders.

Stem cells and cell based therapies have shown tremendous promise; yet controlled studies are still needed in order to confirm its efficacy. Professional judgment and expertise is needed in using these therapies for any therapeutic use, and we urge anyone embarking on the use of stem cell therapies or any regenerative medicine product to consult the national health data bases to evaluate current information from clinical trials. The FDA websites on human tissue should also be consulted to get its current evaluation of any regenerative therapy.

Stem cells, like other medical products that are intended to treat, cure or prevent disease, generally require FDA approval before they can be marketed. FDA has not approved any stem cell-based or regenerative medicine products for use, other than cord blood-derived hematopoietic progenitor cells (blood forming stem cells) for certain indications.

http://www.fda.gov/AboutFDA/Transparency/ Basics/ucm194655.htm

844-548-3966 support@liveyon.com

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Squeezing innovation out of the NASA Twins study: Pipetting and cell isolation in space – Phys.Org

July 11, 2017 NASA immunologist Hawley Kunz performs a microgravity evaluation of the pipetting steps necessary for terrestrial purification of cells. Credit: NASA

Just like early explorers, NASA Twins Study investigators are venturing into new territory. Conducting human omics research on twin astronauts as part of the One Year Mission that took place aboard the International Space Station is one such venture. As technology evolves so does the research. NASA is evaluating more efficient and innovative research techniques to prepare for the journey to Mars.

Innovative thinking could improve the way biological samples are processed and transported from space back to research labs on Earth for future studies. This thinking was prompted by researchers in NASA's Human Research Program (HRP) and Twins Study investigators at Johns Hopkins Medicine.

Freshly isolated samples yield better results than cells isolated from frozen samples returned to Earth from the orbiting laboratory. Pipetting fresh samples at ambient temperature and performing cell isolation on the space station also eliminates the need for expeditious transportation logistics, and allows for more frequent sampling. Once cells are isolated, the samples can be viably frozen and return on any transfer vehicle at any time for further analysis.

On an aircraft that is used as a parabolic flight analog to create short periods of simulated microgravity, Twins Study Investigators Dr. Andrew Feinberg and Lindsay Rizzardi of Johns Hopkins Medicine tested a theory that liquids could be transferred safely in microgravity using a pipettor, which is a slender, graduated measurement tube. Previously researchers thought transferring biological fluids in space could pose risks to precisely controlling the sample.

"This analog demonstrated that pipetting of open fluids is relatively simple and easily controlled and that all fluid transfer steps associated with centrifugation can be replicated in microgravity," Feinberg said. "When dealing with genetic material, research requires precise transfer of liquids among different types of tubes in order to purify DNA, RNA or protein from biological samples to perform molecular analyses."

Coinciding with the fluid transfer research was cell isolation research being conducted by NASA immunologists Brian Crucian, Clarence Sams, Hawley Kunz and NASA astronaut and molecular biologist Kate Rubins. NASA researchers tested terrestrial protocols for cell purification in microgravity using the parabolic flight analog. They found that cell isolation and purification could both be performed in microgravity. Rubins also confirmed some of these findings in space. They published their research with Feinberg and Rizzardi in the July 2016 issue of NPJ Microgravity.

Crucian said, "Laboratory procedures for isolating and purifying cells typically require sensitive gradient centrifugation, careful extraction of isolated cells, and general open pipetting of liquids for washing and transferring the isolated cells."

Being able to transfer fluids and isolate cells in space is significant for a variety of reasons. Mars is a challenging distance from Earth if diagnostics are ever needed of a crewmember. Enabling astronauts to conduct more human research independently could help diagnose an illness more quickly, possibly saving a life in a medical emergency.

As NASA prepares for its journey to Mars, the way researchers handle and processes biological samples in space could change. The protocols validated by the Johns Hopkins and NASA investigators demonstrate that standard cell isolation protocols may indeed be performed in space, something which may enable certain types of genetic, or 'omics', research onboard the space station. Molecular biology technologies such as hand-held sequencers continue to evolve pushing the boundaries of scientific research. HRP will continue to adapt its methodologies to support novel research that protects and ensures the safety of future crews on long-duration missions while opening the door for innovative opportunities.

Explore further: Study examines effects of spaceflight on immune system

More information: Lindsay F Rizzardi et al, Evaluation of techniques for performing cellular isolation and preservation during microgravity conditions, npj Microgravity (2016). DOI: 10.1038/npjmgrav.2016.25

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Squeezing innovation out of the NASA Twins study: Pipetting and cell isolation in space - Phys.Org

Method determines cell age more accurately, could help elderly patients – Medical Xpress

July 11, 2017

Sure, you know how old you are, but what about your cells? Are they the same age? Are they older, younger? Why does it matter?

Led by scientists at the Johns Hopkins University, a team of researchers is reporting progress in developing a method to accurately determine the functional age of cells, a step that could eventually help clinicians evaluate and recommend ways to delay some health effects of aging and potentially improve other treatments, including skin graft matching and predicting prospects for wound healing.

In the current issue of Nature Biomedical Engineering, lead author Jude M. Phillip, who conducted this research while completing his doctorate in chemical and biomolecular engineering at Johns Hopkins, reports success in creating a system that considers a wide array of cellular and molecular factors in one comprehensive aging study.

These results show that the biophysical qualities of cells, such as cell movements and structural features, make better measures of functional age than other factors, including cell secretions and cell energy.

The multidisciplinary team of engineers and clinicians examined dermal cells from just underneath the surface of the skin taken from both males and females between the ages of 2 to 96.

The researchers from Johns Hopkins, Yale University and the National Cancer Institute of the National Institutes of Health hoped to devise a system that through computational analysis could take the measure of various factors of cellular and molecular functions. From that information, they hoped to determine the biological age of individuals more accurately using their cells, in contrast to previous studies, which makes use of gross physiology, or examining cellular mechanisms such as DNA methylation.

"We combined some classic biomolecular hallmarks of aging, and sought to further elucidate the role of biophysical properties of aging cells, all in one study," said Phillip, now a post-doctoral fellow at Weill Cornell Medicine.

Researchers trying to understand aging have up to now focused on factors such as tissue and organ function and on molecular-level studies of genetics and of epigenetics, meaning heritable traits that are not traced to DNA. The level in between - cells - has received relatively little attention, the researchers wrote.

This research was meant to correct for that omission by considering the biophysical attributes of cells, including such factors as the cells' ability to move, maintain flexibility and structure. This focus emerges from the understanding that changes associated with aging at the physiological level - such as diminished lung capacity, grip strength and mean pressure in the arteries - "tend to be secondary to changes in the cells themselves, thus advocating the value of cell-based technologies to assess biological age," the research team wrote.

For example, older cells are more rigid and do not move as well as younger cells, which, among other consequences, most likely contributes to the slower wound healing commonly seen in older people, said Denis Wirtz, the senior author, Johns Hopkins' vice provost for research and the Theophilus H. Smoot Professor of Chemical and Biomolecular Engineering at the Whiting School of Engineering. Wirtz and Phillip conducted their research in the Johns Hopkins Institute for NanoBioTechnology.

From the analysis, they were able to stratify individuals' samples into three groups: those whose cells roughly reflected their chronological age, those whose cells were functionally older, and those whose cells were functionally younger. The results also showed that the so-called biophysical factors of cells determined a more accurate measure of age than biomolecular factors such as cell secretions, cell energy and the organization of DNA.

Phillip explained that this better accuracy from the biophysical factors most likely results from the orchestration of many biomolecular factors. He compared it to the more complete picture you get looking at a forest from a distance without binoculars.

"With binoculars you can see details about the individual trees, the color and shapes of the leaves, the roughness of the bark, the type of tree, but without the binoculars you can now see the density of the trees, and whether there is a barren plot, or a group or dying trees," Phillip said. "This is something you may miss with the binoculars, unless you are looking at the correct spot."

The more accurate system could eventually enable clinicians to see aging in cells before a patient experiences age-related health decline. This in turn could allow doctors to recommend treatments or changes in life habits, such as exercise or diet changes, Wirtz said. Phillip said the work could potentially help clinicians produce more successful skin grafts by matching cell characteristics of the donor and the graft site. Other potential applications range from toxicology screening for cosmetics and topical therapeutics to predicting progression of some age-related diseases.

The researchers acknowledge that the system needs further testing with a larger cell sample, but the results are robust and encouraging. Conducted along with clinicians such as Jeremy Walston, the Raymond and Anna Lublin Professor of Geriatric Medicine, and co-director of the Biology of Healthy Aging program at the Johns Hopkins School of Medicine, this work promises to allow clinicians to measure a person's health in the present and the future.

"It opens the door to finally be able to track how a person is doing at the cellular level," Wirtz said. "This platform is also more than just a cellular age predictor, it has the ability to do so much more in terms of assessing an individual's cellular health," Phillip said.

Explore further: New cellular target may put the brakes on cancer's ability to spread

More information: Jude M. Phillip et al, Biophysical and biomolecular determination of cellular age in humans, Nature Biomedical Engineering (2017). DOI: 10.1038/s41551-017-0093

Most cells can divide only a limited number of times and eventually undergo permanent cell cycle arrest, a state known as cellular senescence. Cellular senescence is mediated by activation of specific cellular signaling pathways ...

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FDA Approves First Sickle Cell Drug in 20 Years – Scientific American

The FDA approved a new medicine Friday to reduce the complications associated with sickle cell disease, a rare blood disorder.

The drug, Endari, is made by privately held Emmaus Medical and is the first new treatment for sickle cell disease to secure FDA approval in almost 20 years. However, the active ingredient in EndariL-glutamineis an old chemical that can be purchased over the counter, which could complicate Emmauss ability to obtain insurance coverage.

In Emmauss pivotal clinical trial, treatment with Endari over 48 weeks reduced the frequency and length of hospital visits for sickle cell pain crises compared to placebo. Commonly reported side effects of the drug included constipation, nausea, and headache.

Sickle cell disease is a rare, inherited disorder characterized by abnormally sickle-shaped red blood cells. These malformed red blood cells clog blood vessels and cut off oxygen to the bodys tissues, leading to episodes of severe pain and organ damage.

Approximately 100,000 people in the U.S. have sickle cell disease, according to the National Institutes of Health.

While Endari focuses on reducing the complications of sickle cell disease, Bluebird Bio is developing a gene therapy to treat the diseases underlying cause and potentially cure patients. Research using the CRISPR gene-editing technology aims to accomplish the same goal.

Other companies working on new, novel drugs targeting sickle cell include Global Blood Therapeutics and Novartis.

Republished with permission fromSTAT. This articleoriginally appearedon July 7, 2017

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FDA Approves First Sickle Cell Drug in 20 Years - Scientific American

Neural stem cells steered by electric fields in rat brain – Medical Xpress

July 11, 2017 Transplants of neural stem cells might be used to treat brain injuries, but how to get them to the right location? UC Davis researcher Min Zhao and Junfeng Feng, a neurosurgeon at Ren Ji Hospital, Shanghai, showed that they can steer transplanted stem cells (green, in inset on right) to one part of a rat's brain using electrical fields. Credit: Junfeng Feng

Electric fields can be used to guide neural stem cells transplanted into the brain towards a specific location. The research, published July 11 in the journal Stem Cell Reports, opens possibilities for effectively guiding stem cells to repair brain damage.

Professor Min Zhao at the University of California, Davis School of Medicine's Institute for Regenerative Cures studies how electric fields can guide wound healing. Damaged tissues generate weak electric fields, and Zhao's research has shown how these electric fields can attract cells into wounds to heal them.

"One unmet need in regenerative medicine is how to effectively and safely mobilize and guide stem cells to migrate to lesion sites for repair," Zhao said. "Inefficient migration of those cells to lesions is a significant roadblock to developing effective clinical applications."

Dr. Junfeng Feng, a neurosurgeon at Ren Ji Hospital, Shanghai Jiao Tong University and Shanghai Institute of Head Trauma, visited Zhao's lab to study how electric fields might guide stem cells implanted in the brain.

Natural neural stem cellscells that can develop into other brain tissuesare found deep in the brain, in the subventricular zone and hippocampus. To repair damage to the outer layers of the brain (the cortex), they have to migrate some distance, especially in the large human brain. Transplanted stem cells might also have to migrate some way to find an area of damage.

Stem Cells Move "Upstream"

Feng and Zhao developed a model of stem cell transplants in rats. They placed human neural stem cells in the rostral migration stream - a pathway in the rat brain that carries cells towards the olfactory bulb, which governs the animal's sense of smell. Cells move along this pathway partly carried by the flow of cerebrospinal fluid and partly guided by chemical signals.

By applying an electric field within the rat's brain, they found that they could get the transplanted stem cells to swim "upstream" against the fluid flow and natural cues and head for other locations within the brain.

The transplanted stem cells were still in their new locations weeks or months after treatment.

"Electrical mobilization and guidance of stem cells in the brain therefore provides a potential approach to facilitate stem cell therapies for brain diseases, stroke and injuries," Zhao said.

Explore further: Distant brain regions selectively recruit stem cells

More information: Jun-Feng Feng et al, Electrical Guidance of Human Stem Cells in the Rat Brain, Stem Cell Reports (2017). DOI: 10.1016/j.stemcr.2017.05.035

Journal reference: Stem Cell Reports

Provided by: UC Davis

Stem cells from bone marrow or fat improve recovery after stroke in rats, finds a study published in BioMed Central's open access journal Stem Cell Research & Therapy. Treatment with stem cells improved the amount of brain ...

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Scientists discover treatment target for pulmonary fibrosis – Medical Xpress

July 11, 2017 by Anna Williams The figure demonstrates how human pathology (top) can be digitized for precision medicine (bottom). Before, we were limited to histologic analysis of lung tissues. Now we can measure the expression of every gene and every cell within that lung and actually digitize that biology, Budinger said. Credit: Northwestern University

In new research published in the Journal of Experimental Medicine, Northwestern Medicine scientists have demonstrated that a unique population of immune cells plays a key role in the development of pulmonary fibrosis. They also showed that targeting such cells could lead to new treatments for the disease.

The study, a collaboration across multiple divisions, departments and schools at Northwestern, was led by Scott Budinger, MD, chief of Pulmonary and Critical Care in the Department of Medicine, and Harris Perlman, PhD, chief of Rheumatology in the Department of Medicine.

Pulmonary fibrosisincluding idiopathic pulmonary fibrosis and scleroderma-associated pulmonary fibrosisis a fatal disease marked by scarring and hardening of lung tissue. The cause is often unknown, and there is currently no effective treatment.

Previously, it was generally accepted in the field that immune cells were unimportant to the development of pulmonary fibrosis. But data from Northwestern's extensive research program in sclerodermaan autoimmune disease closely tied to pulmonary fibrosis that results in hardening of the skinsuggested immune cells may actually play an important role.

To test that hypothesis, the team of scientists utilized next-generation sequencing technologies and novel animal models generated at Northwestern to trace immune cells throughout the progression of pulmonary fibrosis.

They also applied those tools to the analysis of tissue samples collected at Northwestern Medicine hospitals, correlating the animal model data with the patient samples. "One of the strengths of our study is that we go from bench to bedside," Perlman said.

The scientists discovered that a new sub-population of immune cells called monocyte-derived alveolar macrophages were in fact a key driver of disease development in pulmonary fibrosis. Further, the genetic deletion of this population of cells prevented fibrosis in mouse models.

"This will be transformative for the field," said first author Alexander Misharin, MD, PhD, assistant professor of Medicine in the Division of Pulmonary and Critical Care. "Pulmonary fibrosis is a complex diseaseit's not driven by a single gene or cell typebut this study now demonstrates that these immune cells play a key role. This will change the current paradigm."

The findings have important implications for the development of future therapies, especially given that targeting such cells may lead to fewer adverse effects. "These cells are attractive for therapy because they don't need to be there. They aren't necessary for normal function or developmental purposes," said Perlman, also the Mabel Greene Myers Professor of Medicine.

The new methods used in the research could also spark future research in the field.

"This is a novel application of genomic technologies to understanding pulmonary fibrosis," said Budinger, also the Ernest S. Bazley Professor of Airway Diseases and a professor of Cell and Molecular Biology. "By showing that these technologies can be directly applied to patient samples, we offer the promise of incorporating them into personalized medicine approaches. It creates a resource for the research community to develop novel therapies."

The team is now actively deploying these technologies to examine lungs from patients with pulmonary fibrosis, fibrotic skins from patients with scleroderma and joints from patients with rheumatoid arthritis to identify other common immune mechanisms in fibrosis that might be targets for new therapies.

Budinger, Perlman and Misharin are also members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

In a separate finding, the scientists discovered that injury to a mouse early in life permanently altered the immune cell population in the lungs, findings that could have implications for aging research. "Severe injury early in life permanently changes you, in a way that might impact your susceptibility to disease when you get older," Budinger said.

Explore further: Vaccine improves fibrosis in mouse model of idiopathic pulmonary fibrosis

More information: Alexander V. Misharin et al. Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span, The Journal of Experimental Medicine (2017). DOI: 10.1084/jem.20162152

A Yale-led research team has identified an important enzyme that could lead to new therapies for a chronic fatal lung disease that affects hundreds of thousands in the United States each year.

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Researchers identify master molecule behind corneal inflammation – Medical Xpress


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Researchers identify master molecule behind corneal inflammation
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Researchers identify master molecule behind corneal inflammation - Medical Xpress

Regenerating the Body With Stem Cells Hype or Hope? – Labiotech.eu (blog)

When the Japanese researcher Shinya Yamanaka managed to reprogram adult cells into an embryonic-like state to yield induced pluripotent stem cells (iPSCs), this was supposed to herald a revolution in regenerative medicine. But 10 years after their discovery, a therapeutic breakthrough is still outstanding.

The overall stem cell therapy field has failed today to show a very clear cut clinical benefit, told me Georges Rawadi, VP for Business Development at Celyad. The field now needs some significant success to attract attention.

Even though investors prefer placing their bets on the hot T cell therapies these days, some stem cell technologies such as iPSCs are starting to get traction as big industry players are exploring the territory. Last year, Bayer and Versant threw $225M into the pot to launch BlueRock Therapeutics, a regenerative medicine company that plans to develop iPSC-based therapies. A year before, Fujifilm spent $307M to acquire the iPSC company Cellular Dynamics.

Although a big success story is still lagging behind, recent advances in the field argue that stem cells indeed have the potential to translate into effective therapies for currently intractable diseases. Heres an overview of what biotechs stem cells are up to!

Stem cell treatment is not a new concept hematopoietic stem cells (HSCs) were described as early as the 1960s and bone marrow transplants have been used to treat blood cancer for decades.

The reason that we get excited about stem cell therapies comes from our experience with the hematopoietic stem cells. If you want to see what a mature stem cell therapy is like, you only need to look at bone marrow transplantation explained James Peyer, Managing Partner at Apollo Ventures, who has a Ph.D. in stem cell biology.

According to Peyer, the hematopoietic stem cell field is one of the most active areas in the stem cell world right now, mainly fueled by our advances in the gene editing space. Tools like CRISPR and TALEN allow for the genetic modification of a patients own bone marrow stem cells, which can then be expanded and returned to the patient for the correction of a genetic defect.

Last year, regulators gave green light to one of the first therapies of this kind. Strimvelis, developed by GSK, consists of an ex vivo stem cell gene therapy to treat patients with the very rare type of Severe Combined Immunodeficiency (SCID). Using the patients own cells avoids the risk of graft versus host disease (GvHD), which still affects around 30% of people receiving a bone marrow transplant.

Small wonder that the CRISPR companies, CRISPR Therapeutics, Editas, and Intellia are all active in this field, with preclinical programs in a number hematological diseases.

To date, the most prominent stem cells in the clinic are mesenchymal stem cells (MSCs), which are moving through more than 300 registered clinical trials for a wide array of diseases. These cells are able to form a variety of tissues including bone, cartilage, muscle or fat, and can be readily harvested from patients or donors for use in autologous or allogeneic therapies.

While MSCs have deluded the biotech scene with good safety profiles in clinical trials, their actual regenerative potential remains controversial, and there have been a great number of clinical failures, which many blame on a lack of demonstrated mechanisms of action.

As Peyer explained, The problem here is that, as opposed to other adult stem cells, the MSC has been unclearly defined. We know roughly what it does but we dont fully understand the molecular mechanisms driving these cells. On top of being unclearly defined, the regenerative powers of MSCs have been massively over-claimed in the past.

Another reason for the lack of clinical benefit has also been attributed to the use of undifferentiated MSCs, as Rawadi explained to me. The Belgian biotech Celyad, which has been pioneering cell therapy in the cardiovascular space, is using bone-marrow derived autologous MSCs and differentiates them into cardiomyocyte precursors to produce new heart muscle in patients with heart failure.

Although the company missed its primary endpoint in a phase III trial last year, Celyad has staked out a patient subpopulation that showed significant improvement. Its technology still has the confidence of the FDA, which just handed out a Fast Track designation and Celyad is now planning a refined Phase III trial.

One of Celyads major competitors, Australian Mesoblast, is forging ahead using allogeneic MSCs with Phase III programs in heart failure, chronic low back pain (CLBP) due to disc degeneration, as well as a range of inflammatory conditions including GvHD and rheumatoid arthritis.

Although the ability of MSCs to regenerate tissues remains questionable, the Mesoblasts approach hinges on a body of evidence showing that MSCs can suppress inflammation and mobilize endogenous repair mechanisms through indirect effects on immune cells.

Indeed, the first-ever approved stem cell therapy, Prochymal, also depends on this mechanism. Prochymal was developed by US-based Osiris Therapeutics and in 2012 received Canadian approval to treat acute GvHD. But after Sanofi opted to shelve its partnership with Osiris prior to FDA approval, the biotech sold out its off-the-shelf stem cell platform to Mesoblast in a $100M deal.

In Belgium, companies like TiGenix and Promethera are also banking on the immunomodulatory properties of MSCs. The companies are developing treatments for patients with Crohns disease and liver diseases, respectively.

The ultimate hope for stem cell therapies has been to regenerate damaged or diseased tissues as found in diabetes, heart failure or blindness. Holostem Terapie Avanzate, a spin-off from the University of Modena and Reggio Emilia was the first company to move towards this goal.

Building on 20 long years of research, the biotech has developed Holoclar, the first and only autologous stem cell therapy (apart from bone marrow transplants) to enter the European market. Holoclar is based on limbal stem cells, located in a part of the eye called the limbus, which can be used to restore eyesight in patients that have lost sight due to burn injuries.

Meanwhile, UK-based Reneuron is developing off-the-shelf therapies that aim to restore the cognitive function of patients following a stroke. Backed by no other than Neil Woodford, the company recently raised an impressive 100M to advance its lead therapy to the market.

The biotechs fetal-derived neural stem cell line CTX was able to significantly reduce the disability of post-stroke patients in a Phase II trial and ReNeuron is now planning to push its candidate into pivotal trials.

A major question in the space a decade ago was safety. Today, theres been a lot of trials done that show that safety is not an issue. I think safety is kind of off the table but efficacy is still a question mark. And thats what were trying to deliver now, Olav Helleb, CEO of ReNeuron, told me.

While neural stem cells and other tissue-specific stem cells are able to regenerate the cells of a particular tissue, Embryonic Stem Cells (ESCs) and their engineered counterparts, iPSCs, are capable of making every cell type in the body, a property known as pluripotency. Pluripotent stem cells can also expand indefinitely in culture and their identification unlocked massive expectations for these cells to transform the regenerative medicine field.

Yet, these cells come with significant challenges associated with the safety of the final preparation. Apart from ethical issues surrounding ESCs, today, a lot of companies have been cautious about using these cells for therapy, because undifferentiated pluripotent cells can drive tumor formation, explained Rawadi. Since ESCs can, in principle, form every cell type, they can lead to the formation of teratomas.

A major reason for the fairly slow progress in the field is based on the difficulties of directing a pluripotent cell to exactly the cell type that is needed for cell therapy. We can readily drive the cells from the undifferentiated state to the differentiated state. However, getting those cells to pause anywhere in the middle of this continuum to yield progenitor cells is incredibly challenging, Peyer explained. Another challenge, he says, is to engraft the cells in the right place to enable them to become fully integrated.

Besides initial hurdles, companies like US-based Asterias or ViaCyte are now running the first Phase I/II trials with ESC-derived cells to treat patients with spinal cord injuries and to restore the beta cells in type I diabetes. So far, the eye has been the the dominant organ for many of the first human clinical trials with pluripotent stem cells, where the cells are assessed in diseases such as age-related macular degeneration (AMD) to restore the loss of the retinal epithelium.

Deriving retinal epithelium from pluripotent cells is relatively easy and in fact, researchers in Japan are now running the very first clinical trial using donor-derived iPSCs to treat patients with AMD. For reasons of safety and standardization, the trial is based on an allogeneic approach. However, since this doesnt offer an exact genetic match, allogeneic therapies raise the prospect of immune rejection, an issue that has been plaguing the use of ESCs.

But the scientists in Japan have contended that iPSC banks could potentially solve this problem. The team in Japan is currently establishing an iPSC bank, consisting of HLA-characterized cell lines from 5-10 different donors, which should match 3050% of Japans population.

Such haplobanks have the benefits of allogeneic cell therapy, namely cost-effectiveness and standardization, but you still have matching immune systems, Peyer agrees.

For now, this remains a vision for the future, but the potential seems enormous. As Julian Howell, CMO of ReNeuron, told me, iPSCs have still got an awful long way to go. For the iPSC program running in Japan, they recently acknowledged that it took about $1.5M and 6 months to treat each patient. Its a great idea but its still got some way to go before it reaches the scale that could get into the clinic.

Images via nobeastsofierce,Natali_ Mis,vchal/ Shutterstock

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Regenerating the Body With Stem Cells Hype or Hope? - Labiotech.eu (blog)

Broomfield’s Regenexx in merger with Iowa company – Boulder Daily Camera

Dr. John Schultz gives an injection of bone marrow derived stem cells into the knee of patient Steve Brink from Washington state at the Regenexx offices in Broomfield June 12. (Paul Aiken / Staff Photographer)

_Broomfield's Regenexx, a stem cell treatment network, has completed its merger with Des Moines, Iowa-based Harbor View Medical.

The company corporate headquarters will move to Des Moines as a result, with the company's medical headquarters remaining in Broomfield, according to spokeswoman Caroline Patterson.

Patterson there would be no layoffs in Broomfield as a result of the merger.

Regenexx co-founder, Dr. Christopher Centeno, a pioneer in using stem cells to treat orthopedic injuries, will maintain his role as chief medical officer and Jason Hellickson will become CEO.

Regenexx treatments include injection of a patient's own stem cells and platelet-rich plasma (PRP) to encourage healing of tendons, joints and muscles.

"Most of what we currently call orthopedic surgery will, in the next 10-20 years, be in the dust bin of history," Centano told the Daily Camera last month. "Thirty years from now, cutting people open and drilling holes will be considered barbaric."

Despite advances in research, critics say the safety and effectiveness of these regenerative treatments is largely unregulated and remains poorly understood.

A study by Mayo Clinic, whose results were published last year, noted that patients in a blind study, who had arthritis in both knees, saw benefits from the treatment, but that it wasn't clear why. Just one knee had actually been injected with the stem cells.

The stem cell treatments,have generated controversy among some medical professionals because they cost thousands of dollars and have not been widely studied. Last year the U.S. Food and Drug Administration (FDA) held a series of scientific meetings examining how best to regulate and ensure the safety and efficacy of this approach.

The Mayo Clinic study, overseen by the FDA, concluded that the procedure it sstudied was safe to undergo, but it was not ready to recommend it for "routine arthritis care."

Still the use of stem cell treatments in everything from veterinary clinics to dermatology orthopedic practices is growing. Founded in 2005, Regenexx lists 48 clinics worldwide, including a new facility it opened in Mumbai this month.

Jerd Smith: 303-473-1332, smithj@dailycamera.com or twitter.com/jerd_smith

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Broomfield's Regenexx in merger with Iowa company - Boulder Daily Camera