Category Archives: Cell Medicine

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Welcome to the Department of Cell Biology and Physiology in the School of Medicine at the University of North Carolina at Chapel Hill where our mission is to be nationally recognized for excellence in our discipline by Leading, Teaching and Caring.

LeadingWe conduct cutting-edge, innovative research that advances the discipline of cell biology and physiology, with an emphasis on topics that contribute to the improvement of human health. The UNC-CH Department of Cell Biology and Physiology is nationally-recognized and ranked #2 in the country for our level of NIH funding in 2016! The Department comprises over 35 basic science laboratories dedicated to integrative research in areas related to neuroscience, cardiovascular development and disease, cell motility, cellular cytoskeleton and intracellular trafficking, gastrointestinal biology, cellular mechanisms of aging and cancer biology. I encourage you to browse our website, which highlights each individual faculty research program. Our faculty, trainees and staff benefit from robust partnerships with numerous Centers across campus including the Lineberger Comprehensive Cancer Center, McAllister Heart Institute, Marsico Lung Institute and Thurston Arthritis Research Center, to name a few.

TeachingWe provide a rigorous and competitive educational experience for a diverse population of graduate and professional trainees which enables them to succeed in their future careers. The Department has a long tradition of successfully training the next generation of scientists. Our newly-launched Curriculum in Cell Biology and Physiology offers an integrated training program for PhD students. In addition, the Department is home to a multitude of undergraduate, medical and clinical fellow trainees who are seeking avenues for intellectually-engaging and creative research experiences. Research scientists who train in the discipline of cell biology and physiology will benefit from being able to synergize their training from several vantage points. For example, the development of sophisticated genetic engineering tools enables us to test focused hypotheses on the multi-cellular diversity of organs and their cellular compositions. Likewise, these same genetic techniques, coupled with the ability to image cell behavior at unprecedented resolution and the application of -omics approaches, permits a broader exploration into how cells sense and respond to their environments, either within an organ or in response to different pathophysiological conditions. In these ways, research trainees in our Department can capitalize on rapid technological advances and successfully apply their findings to inform the fundamental processes of normal and pathological physiology and cell biological behaviors.

CaringWe serve the people of North Carolina, the United States and the international community, by excelling in our research and educational missions thereby promoting the health and well-being of individuals and communities locally, nationally and internationally. The Department of Cell Biology and Physiology has a strong commitment to fostering an environment of inclusion, diversity and wellness within the workplace, which lays the foundation for collaborative partnerships and creative exploration. We provide award-wining mentoring and professional development activities for individuals at all career stages. Our faculty and trainees actively participate in local and national service, giving back to our communities.

It is an exciting time for the Department, with six new faculty hires, the launch of our state-of-the-art Hooker Imaging Core Facility and remarkable accolades and recognition of our distinguished faculty and trainees. I hope that you will enjoy exploring our research and educational programs, and encourage you to contact us if you would like to join and support our missions.

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Department of Cell Biology and Physiology, School of ...

A fast and cost-efficient technique for harvesting stem cells may have the potential to revolutionise the way vets treat orthopaedic conditions in horses.

The regenerative therapy, called Lipogems, uses fat tissue-derived mesenchymal stem cells from the tail head of the patient, which is prepared using a stable-side kit, meaning the procedure can be carried out immediately.

Historically, vets wanting to obtain stem cells would have to harvest fat tissue or bone marrow from the patient and send it to a laboratory for the cells to be cultivated and prepared for injection at another consultation a process that could take weeks and delay treatment.

In comparison, Lipogems allows the transplanting of lipoaspirate from fat tissue within 20 to 30 minutes of harvesting, said Lipocast Biotech UK, the company responsible for introducing the technique to the veterinary market for the first time.

Conditions treated to date include lesions of the superficial and deep flexor tendons, suspensory ligament desmitis (proximal, body and branch lesions), check ligament injuries and osteoarthritis affecting distal interphalangeal, fetlock and stifle joints.

Vet Tim Watson, of Waterlane Equine Vets in Gloucestershire, led initial work on the project.

In the past, people have cultured stem cells from fat tissues, but what this technique offers for the first time is the ability to extract stem cells in a quick, easy and relatively cost-effective way, so you can treat the horse immediately, Dr Watson said.

The technique means stem cell cultivation techniques are no longer the preserve of hospitals and laboratories.

Dr Watson said: Vets out on the road can do it. Potentially, it could revolutionise the way we treat orthopaedic conditions in horses.

There is nothing comparable with this technique in the industry.

Original post:
Vet: stem cell technique could revolutionise equine medicine - vet times

A French teen who underwent a first-of-its-kind procedure 15 months ago to change his DNA shows no signs of the sickle cell disease he had been suffering from. The procedure, which was performed at Necker Childrens Hospital in Paris, may offer hope to millions of patients who suffer from sickle cell disease, BBC News reported.

Sickle cell disease is a severe hereditary form of anemia, which causes patients to develop abnormal hemoglobin in red blood cells. The botched hemoglobin causes the cells to form a crescent or sickle shape, making it difficult to maneuver throughout the body. Sickle-shaped cells are less flexible, and may get stuck to vessel walls causing a blockage, which can stop blood flow to vital tissues.

Before undergoing the procedure, treatment for the unidentified teen included traveling to the hospital each month for a blood transfusion to dilute the defective blood, BBC News reported. According to the report, the excessive amount of treatment caused severe internal damage, and at age 13 he already needed a hip replacement and had his spleen removed.

In a world first, doctors at Necker Childrens Hospital removed his bone marrow and genetically altered it using a virus to compensate for the defect in his DNA responsible for sickle cell disease, BBC News reported. The results published in the New England Journal of Medicine said he no longer uses medication, and has been making normal blood for the past 15 months.

So far the patient has no sign of the disease, no pain, no hospitalization, Philippe Leboulch, professor of medicine at the University of Paris, told BBC News. He no longer requires a transfusion so we are quite pleased with that.

Doctors said the treatment will have to be repeated in other patients as the teen is the trials first, but that it does show powerful potential.

Ive worked in gene therapy for a long time and we make small steps and know theres years more work, Dr. Deborah Gill, of the gene medicine research group at the University of Oxford, told BBC News. But here you have someone who has received gene therapy and has complete clinical remission thats a huge step forward.

It was not clear how much the procedure would cost, or whether there are plans to expand to other countries.

Read more from the original source:
Doctors reverse teen's sickle cell disease with innovative gene therapy - Fox News

The artificial structure shows promise as a tool for medical research, though it cannot develop into an actual baby.

After an egg is fertilized by a sperm, it begins to divide multiple times. This process generates a small, free-floating ball of stem cells: a blastocyst.

Within a mammalian blastocyst, the cells that will become the body of the embryo (embryonic stem cells) begin to cluster at one end. Two other types of cells, the extra-embryonic trophoblast stem cells and the endoderm stem cells, begin to form patterns that will eventually become a placenta and a yolk sac, respectively.

To develop further, the blastocyst has to implant in the womb, where it transforms into a more complex architecture. However, implantation hides the embryo from view -- and from experimentation.

In the study, Zernicka-Goetz wanted to replicate developing embryonic events using stem cells.

Other scientists who have attempted the same thing have used only embryonic stem cells, but these experiments, though they have yielded embryoid bodies, have not been entirely successful. The artificial bodies never follow the same chain of events found in nature, and they lack the structure of a natural embryo.

Zernicka-Goetz, a professor in Cambridge's Department of Physiology, Development and Neuroscience, hypothesized that the trophoblast stem cells communicate with the embryonic stem cells and guide their development.

She and her colleagues placed embryonic and trophoblast stem cells within an extra-cellular matrix: the non-cell component found in all tissues and organs that provides biochemical support to cells. This formed a scaffold on which the two stem cell types could co-develop.

The embryonic stem cells sent chemical messages to the trophoblast stem cells and vice versa, said Zernicka-Goetz. Essentially, the different stem cells began to "talk to each other," and this helped the embryonic stem cells, she explained.

"They respond by turning on particular developmental gene circuits or by physically changing shape to accomplish some architectural remodeling," she wrote in an email. "This happens in normal embryogenesis and it is what we are trying to recreate in the culture dish."

Ultimately, the cells organized themselves into a structure that not only looked like an embryo, it behaved like one, with anatomically correct regions developing at the right time and in the right place.

"The results were spectacular -- they formed structures that developed in a way strongly resembling embryos in their architecture and expressing specific genes in the right place and at the right time," Zernicka-Goetz wrote.

Despite its resemblance to a real embryo, this artificial embryo will not develop into a healthy fetus, the researchers said. That would require the endoderm stem cells, which "does other things that are most likely necessary for further development," said Zernicka-Goetz.

"Whether adding these to the system would be enough to achieve further development, I don't know," she said.

"Correct placental development" is essential for proper implantation into "either the womb or a substitute for the womb," she said. "To achieve this will be some time off."

According to Dr. Christos Coutifaris, president-elect of the American Society for Reproductive Medicine and a professor at the University of Pennsylvania, the new study is significant because it shows how "the cells that are extra-embryonic -- the ones that are going to give rise to the placenta -- actually play a role" in the development of cells that eventually become the fetus.

"It's not two completely separate entities," Coutifaris said, referring to the embryo and its support structure. Understanding how the two types of cells interact and the chemical signals they exchange is "really, really critical."

Zernicka-Goetz's model has practical applications in research, where it can be used to better understand the conversation between embryonic stem cells and trophoblast stem cells, he said. "You can manipulate these cells molecularly to try to understand these interactions and how early development occurs pre-implantation."

According to Kyle E. Orwig, an associate professor of obstetrics, gynecology and reproductive sciences, and molecular genetics and biochemistry at the University of Pittsburgh, Zernicka-Goetz's model "will enable investigators to investigate the effects of genetic manipulations, environmental toxins, therapeutics and factors on embryo development." Artificial embryos "represent a powerful tool for research that might reduce (but not eliminate) the need for human embryos," Orwig said.

Dr. David Adamson, a reproductive endocrinologist, an adjunct clinical professor at Stanford University and chairman of the International Committee Monitoring Assisted Reproductive Technologies, believes that it's "very important to continue to do basic science research in reproductive medicine."

"How our species reproduces is very important to know," Adamson said. "When you learn about reproduction and learn how cells reproduce and how cells differentiate and what makes things happen normally and what makes thing happen abnormally, then there clearly are a lot of potential therapeutic applications."

Past advances in reproductive medicine have helped scientists prevent genetic-based diseases, he said. Specifically, in vitro fertilization techniques have allowed doctors to biopsy and conduct genetic tests on embryos to prevent inherited illnesses, including Huntington's.

In vitro fertilization is "fundamentally transformative," said Adamson, who sees the new research as adding to the wealth of knowledge about this procedure.

In fact, Zernicka-Goetz works in the same nondescript brick building on the Cambridge campus where Robert Edwards, a reproductive medicine pioneer, once toiled. Edwards developed the Nobel Prize-winning technique of in vitro fertilization, which eventually resulted in the birth of the first "test tube" baby, Louise Brown.

Helping families have babies is the most obvious contribution of in vitro fertilization. Today, Adamson said, there have been approximately 6.5 million babies born using in vitro fertilization since the procedure was first developed. An exact number is not known because many countries, including China, do not have registries to count them, explained Adamson.

Meanwhile, Zernicka-Goetz said she will continue her work on embryonic development as she and the members of her lab are "totally driven by a curiosity to understand these fundamental aspects of life."

She plans to use human stem cells to create a similar embryonic model. Then she plans to use that model to learn more about normal embryonic development and understand when it goes wrong without needing to experiment on an actual human embryo.

The work also "continually teaches us about the properties of stem cells," Zernicka-Goetz said. She added that this knowledge is useful for developing "therapies to replace faulty tissues in so-called regenerative medicine."

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Artificial embryo shows early potential for medical therapies, not babies - CNN

The natural lifecycle of cells that line the intestine is critical to preserving stable conditions in the gut, according to new research led by a Weill Cornell Medicine investigator. The findings may lead to the development of new therapies to alleviate inflammatory bowel disease (IBD) and other chronic inflammatory illnesses.

In the study, published Nov. 9 in Nature, the scientists investigated the healthy turnover of epithelial cells, which are born and die every four to five days, to better understand how the gut maintains a healthy equilibrium. Because cells, called phagocytes, can clear dying cells so quickly in the body, it had been difficult to study this process in tissues. The inability to clear dying cells has been linked to inflammation and autoimmunity. Dying epithelial cells are shed into the gut lumen, so their active clearance is not necessary and they were thought to have no role in intestinal inflammation.

The investigators sought to understand whether phagocytes can take up dying epithelial cells in the gut and, if so, how these phagocytes respond. Specifically, the study tried to ascertain which genes are expressed by phagocytes after the uptake of dead cells. To answer these questions, the scientists engineered a mouse model where they could turn on apoptosis and catch phagocytes in the act of sampling dying cells. Through a series of experiments, they found that several of the genes modulated up or down in phagocytes bearing dead cells overlapped with the same genes that have been associated with susceptibility to IBD.

The mouse model used in the study enables the visualization of a dying red cell within the green fluorescently-labeled small intestinal epithelial cells. The green outline of villi shown delineates the single cell layer of the intestinal epithelium. Cell nuclei are shown in blue. Weill Cornell Medicine investigators tracked dying intestinal epithelial cells into the underlying phagocytes (not visible), and asked how their uptake modulates gene expression in those phagocytes.

The fact that there was an overlap shows that apoptosis must play a role in maintaining equilibrium in the gut, said Dr. Julie Magarian Blander, a senior faculty member in the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine who was recently recruited as a professor of immunology from Mount Sinai. This study identified cell death within the epithelium as an important factor to consider when thinking about therapeutic strategies for patients with IBD.

In their experiments, the scientists expressed a green fluorescent protein fused to the diphtheria toxin receptor within intestinal epithelial cells of mice, which made them visible under a microscope and sensitive to diphtheria toxin. They injected into these mice a carefully titrated dose of toxin into the intestinal walls of mice to induce cell death. Then the team examined the phagocytes that turned green after they internalized dead cells. Macrophages, one kind of phagocyte, expressed genes that help process the increased lipid and cholesterol load they acquired from dying cells. Dendritic cells, another type of phagocyte, activated genes responsible for instructing the development of regulatory CD4 T cells, a class of suppressive white blood cells. Notably, both phagocytes expressed a common suppression of inflammation gene signature.

Because the same genes that confer susceptibility to IBD were modulated in response to apoptotic cell sampling, the research indicates that a disruption of the phagocytes immunosuppressive response would have consequences for homeostasis or stable conditions in the gut.

We know there is excessive cell death, inflammation and microbial imbalance in IBD, so the prediction is that the immunosuppressive program in phagocytes, associated with natural cell death in the gut epithelium, would be disrupted, Dr. Blander said. The goal in the treatment of IBD is to enhance healing in the gut, but now we know that this also helps phagocytes restore their immunosuppressive and homeostatic functions. We think this would translate into helping patients stay in remission. Theres a lot to learn from phagocytes and we may be able to target the same pathways they use to suppress inflammation in patients with IBD.

The study validates the importance of healing in the mucosa, or lining, of the intestine as a therapy and enhances the understanding of that process. The next phase of Dr. Blanders research will be to investigate how the inflammatory conditions of IBD alter cell death and the homeostatic immunosuppressive functions of intestinal phagocytes, and to do so in both mouse models and different groups of IBD patients undergoing anti-TNF therapy at the Jill Roberts Center for Inflammatory Bowel Disease at New York-Presbyterian and Weill Cornell Medicine.

Read this article:
Cell Death in Gut Implicated in IBD - Cornell Chronicle

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Foundation Medicine, Inc. (NASDAQ:FMI) today announced that it has received payment from Palmetto GBA, the Companys Medicare Administrative Contractor (MAC) in North Carolina, for its FoundationOne comprehensive genomic profiling assay when used in the clinical course of care for individuals in the United States with Stage IIIB/IV non-small cell lung cancer (NSCLC) who meet the eligibility requirements under Palmetto GBAs Local Coverage Determination L36143 (LCD). The LCD was most recently updated on December 22, 2016. Foundation Medicine began submitting an initial set of claims to Palmetto GBA in January 2017 for FoundationOne, and received its first payments for claims under this LCD on March 1, 2017.

Coverage and payment for FoundationOne under Palmetto GBAs LCD is a positive step toward advancing access to precision medicines for individuals living with non-small cell lung cancer, said Troy Cox, chief executive officer for Foundation Medicine. We look forward to continuing to work with Palmetto GBA as we gain additional payment experience under this LCD for non-small cell lung cancer. We will continue to work with FDA and CMS as they review our universal companion diagnostic test through the Parallel Review process with the goal of being the first pan-cancer, universal companion diagnostic test to receive FDA approval and a National Coverage Determination from CMS.

About Foundation Medicine Foundation Medicine (NASDAQ:FMI) is a molecular information company dedicated to a transformation in cancer care in which treatment is informed by a deep understanding of the genomic changes that contribute to each patient's unique cancer. The company offers a full suite of comprehensive genomic profiling assays to identify the molecular alterations in a patient's cancer and match them with relevant targeted therapies, immunotherapies and clinical trials. Foundation Medicines molecular information platform aims to improve day-to-day care for patients by serving the needs of clinicians, academic researchers and drug developers to help advance the science of molecular medicine in cancer. For more information, please visit http://www.FoundationMedicine.com or follow Foundation Medicine on Twitter (@FoundationATCG).

Cautionary Note Regarding Forward-Looking Statements for Foundation Medicine

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding reimbursement of the Companys comprehensive genomic profiling assays, the benefits provided by anFDA-approved and CMS-covered version of the Companys universal companion diagnostic test, and progress with the Parallel Review process with FDAand CMS; the scope and timing of any approval of FoundationOne as a medical device by FDAand any potential national coverage decisions by CMS; and strategies for achievingMedicarecoverage decisions at the local or national level and new and expanded coverage from third-party payers.All such forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include the risks that FDA does not approve our universal companion diagnosic test as a medical device or that CMS does not decide to offer our universal companion diagnostic test as a covered benefit underMedicare; FDAor CMS is delayed in the completion of the Parallel Review process; and the risks described under the caption "Risk Factors" inFoundation Medicine's Annual Report on Form 10-K for the year endedDecember 31, 2016, which is being filed with the Securities and Exchange Commission on the date hereof, as well as other risks detailed inFoundation Medicine'ssubsequent filings with theSecurities and Exchange Commission. All information in this press release is as of the date of the release, andFoundation Medicine undertakes no duty to update this information unless required by law.

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Foundation Medicine Receives Medicare Payment in Non-Small ... - Business Wire (press release)

SEOUL, South Korea--(BUSINESS WIRE)--R-Japan, an affiliated company of Nature Cell (KOSDAQ: 007390), announced its business performance for 2016.

In 2016 R-Japan cultured and supplied a total of 1,055.9 billion stem cells for 5 affiliated hospitals including Nishihara Clinic. The company conducted regenerative medical treatment more than 3,500 times and achieved sales of KRW10.4 billion as well as the ordinary profit of KRW1.6 billion.

The patients who received the regenerative medical treatment with stem cells supplied by R-Japan did not have any side effects. This performance of the medical treatment for the past 1 year has been officially reported to Japans Ministry of Health, Labor and Welfare.

Moreover, the medical treatments effects regarding degenerative arthritis, critical limb ischemia, autoimmune disease and skin care have been gradually acknowledged. R-Japan reported the number of medical treatments for degenerative arthritis exceeded 650 and the satisfaction regarding its therapeutic effect was very high.

R-Japan is promoting the expansion of affiliated medical institutions in 27 regions including Hokkaido, Kansai, Kyushu, etc., expecting the earnest activation of the stem cell regenerative medical treatment in 2017. Moreover, the company is planning to expand the area of medical treatment to anti-aging and Alzheimers disease. The company expects to perform regenerative medical treatment more than 5,000 times and supply cells which will be worth more than 1.5 trillion won for this year.

From this March, production processes will be allocated to Nature Cell and the affiliated company R Bio, which received permission for manufacturing from Japans Ministry of Health, Labor and Welfare. Japan BioStar Stemcell Research Institute (Director: Jeong-chan Ra) will be established in the KOBE Biomedical Innovation Cluster.

About R-JAPAN

R-JAPAN Co., Ltd. is the advanced biotechnology company specialized in manufacturing mesenchymal stem cells regenerative therapy with stem cell technology of Biostar Stem cell Research Institute in Korea. R-Japans proprietary technology is to isolate, multiply, and store adult mesenchymal stem cells with ensuring genetic integrity. R-Japan currently cultures approximately 1,000 cases per month and has been evaluated by many medical institutions. As a result, R-Japan has been cultured 5,860 billion cells for 24,293 patients since stem cell processing facility was operated.

Read more:
R-Japan Leads Japan's Regenerative Medicine Technology with Korean Autologous Fat Stem Cell Culture Technology - Business Wire (press release)

WEDNESDAY, March 1, 2017 (HealthDay News) -- Researchers are reporting early success using gene therapy to treat, or even potentially cure, sickle cell anemia.

The findings come from just one patient, a teenage boy in France. But more than 15 months after receiving the treatment, he remained free of symptoms and his usual medications.

That's a big change from his situation before the gene therapy, according to his doctors at Necker Children's Hospital in Paris.

For years, the boy had been suffering bouts of severe pain, as well as other sickle cell complications that affected his lungs, bones and spleen.

Medical experts stressed, however, that much more research lies ahead before gene therapy can become an option for sickle cell anemia.

It's not clear how long the benefits will last, they said. And the approach obviously has to be tested in more patients.

"This is not right around the corner," said Dr. George Buchanan, a professor emeritus of pediatrics at the University of Texas Southwestern Medical Center in Dallas.

That said, Buchanan called the results a "breakthrough" against a disease that can be debilitating and difficult to treat.

Buchanan, who wasn't involved in the research, helped craft the current treatment guidelines for sickle cell.

"This is what people have been wanting and waiting for," he said. "So it's exciting."

Sickle cell anemia is an inherited disease that mainly affects people of African, South American or Mediterranean descent. In the United States, about 1 in 365 black children is born with the condition, according to the U.S. National Heart, Lung, and Blood Institute.

It arises when a person inherits two copies of an abnormal hemoglobin gene -- one from each parent. Hemoglobin is an oxygen-carrying protein in the body's red blood cells.

When red blood cells contain "sickle" hemoglobin, they become crescent-shaped, rather than disc-shaped. Those abnormal cells tend to be sticky and can block blood flow -- causing symptoms such pain, fatigue and shortness of breath. Over time, the disease can damage organs throughout the body.

There are treatments for sickle cell, such as some cancer drugs, Buchanan pointed out, but they can be difficult to manage and have side effects.

There is one potential cure for sickle cell, Buchanan said: a bone marrow transplant.

In that procedure, doctors use chemotherapy drugs to wipe out the patient's existing bone marrow stem cells -- which are producing the faulty red blood cells. They are then replaced with bone marrow cells from a healthy donor.

A major problem, Buchanan said, is that the donor typically has to be a sibling who is genetically compatible -- and free of sickle cell disease.

"We've known for a long time that bone marrow transplants can work," Buchanan said. "But most patients don't have a donor."

That's where gene therapy could fit in. Essentially, the aim is to genetically alter patients' own blood stem cells so they don't produce abnormal hemoglobin.

In this case, the French team, led by Dr. Marina Cavazzana, of Necker Children's Hospital's biotherapy department, focused on a gene called beta globin. In sickle cell anemia, beta globin is mutated.

First, the researchers extracted a stem cell supply from their teen patient's bone marrow, before using chemotherapy to wipe out the remaining stem cells.

Then they used a modified virus to deliver an "anti-sickling" version of the beta globin gene into the stem cells they'd removed pre-chemo. The modified stem cells were infused back into the patient.

Over the next few months, the boy showed a growing number of new blood cells bearing the mark of the anti-sickling gene. The result was that roughly half of his hemoglobin was no longer abnormal.

In essence, Buchanan explained, the therapy "converted" the patient to sickle-cell trait -- that is, a person who carries only one copy of the abnormal hemoglobin gene. Those individuals don't develop sickle cell disease.

"This is encouraging," said Dr. David Williams, president of the Dana-Farber/Boston Children's Cancer and Blood Disorders Center.

But, he cautioned, "the caveat is, this is one patient, and 15 months is a short follow-up."

Williams and his colleagues are studying a different approach to sickle cell gene therapy. It aims to restart the body's production of healthy fetal hemoglobin -- to replace the abnormal "adult" hemoglobin seen in sickle cell.

The hope, Williams said, is that gene therapy will ultimately offer a one-time treatment that cures sickle cell. But no one knows yet whether that will happen.

According to Williams, two key questions are: What's the long-term safety? And will the altered stem cells last for a patient's lifetime?

If gene therapy is proven to work, there will no doubt be practical obstacles to its widespread use, according to Buchanan. It's a high-tech treatment, and many sickle cell patients are low-income and far from a major medical center, he said.

But, Buchanan said, the new findings have now "opened a door."

The study was partly funded by Bluebird Bio, the company developing the therapy.

The results were published March 1 in the New England Journal of Medicine.

Read more:
Gene Therapy: A Breakthrough for Sickle Cell Anemia? - Montana Standard

March 3, 2017 by Jeff Norris

A molecular key to aging of the blood and immune system has been discovered in new research conducted at UC San Francisco, raising hope that it may be possible to find a way to slow or reverse the growing risk for aging-associated chronic inflammatory diseases, anemia, blood cancers, and life-threatening infections.

The key is a link between the health of a rare population of adult stem cells that arise early in development and are responsible for replenishing all blood cell types throughout a lifetime, and a newly identified role for autophagy, an important cellular cleanup and recycling process that was the focus of the 2016 Nobel Prize in Physiology or Medicine.

In their new study, published online March 1 in Nature, the UCSF team discovered that in addition to its normal role in cellular waste-processing, autophagy also is needed for the orderly maintenance of blood-forming hematopoietic stem cells (HSCs), the adult stem cells that give rise to red blood cells, which carry oxygen, and to platelets, which prevent bleeding, as well as the entire immune system, which fights infections and disposes of pathogens.

The researchers found that autophagy keeps HSCs in check by allowing metabolically active HSCs to return to a resting, quiescent state akin to hibernation. This is the default state of adult HSCs, allowing their maintenance for a lifetime.

According to Emmanuelle Passegu, PhD, the senior scientist for the study, "This is a previously unknown role for autophagy in stem cell biology."

Failure to activate autophagy has profound impacts on the blood system, Passegu's team found, leading to the unbalanced production of certain types of blood cells. Defective autophagy also diminished the ability of HSCs to regenerate the entire blood system when they were transplanted into irradiated mice, a procedure similar to bone marrow transplantation.

The researchers determined that 70 percent of HSCs from old mice were not undergoing autophagy, and these cells exhibited the dysfunctional features common among old HSCs. However, the 30 percent of old HSCs that did undergo autophagy looked and acted like HSCs from younger mice.

Passegu led the study while she was a professor of medicine with the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCSF. In January she became an Alumni Professor in the Department of Genetics & Development and the director of the Columbia Stem Cell Initiative at Columbia University Medical Center.

Therapies for Rejuvenating Aging Blood and Immune Systems Scientists have identified many different tissue-specific stem cells, all of whose performance declines with age, Passegu said. Finding out how this occurs has been an active area of research, and a focus of her laboratory group in recent years.

In a large series of experiments and analyses, many conducted by the study's first author, Theodore Ho, a UCSF graduate student, the scientists compared characteristics of HSCs from old mice with those of HSCs from younger mice that had been genetically programmed so that they could not undergo autophagy. They found that loss of autophagy in young mice was sufficient to drive many of the defects that arise naturally in the blood of old mice, including changes in the cellular appearance of HSCs and a disruption in the normal proportions of the various types of blood cells, characteristics of old age.

Previous research had shown that autophagy causes the formation of "sacs" within cells that can engulf and enzymatically digest molecules and even major cellular structures, including mitochondria, the cell's biochemical power plants. But in the new study, the researchers found that genetically programmed loss of autophagy resulted in the accumulation of activated mitochondria with increased oxidative metabolism that triggered chemical modifications of DNA in HSCs.

These "epigenetic" DNA modifications altered the activities of genes in a way that changed the developmental fate of HSCs. They triggered disproportionate production of certain blood cells and reduced the ability of HSCs to regenerate the entire blood system when transplanted. This result was similar to what the researchers observed in the majority of old HSCs that failed to activate autophagy.

In contrast, the minority of old HSCs that still exhibited significant levels of autophagy were able to keep their mitochondria and metabolism in check, and could re-establish a healthy blood system following transplantation, similar to HSCs from young mice.

However, in a hopeful sign for potential future therapies to rejuvenate blood stem cells, the researchers succeeded in restoring autophagy to old HSCs by treating them with pharmacological agents in a lab dish.

"This discovery might provide an interesting therapeutic angle to use in re-activating autophagy in all of the old HSCs, to slow the aging of the blood system and to improve engraftment during bone marrow or HSC transplantation," Passegu said. "It is our hope that the end point will be a way to really improve the fitness of stem cells and to use that capability to help the elderly by preventing the development of blood cancers and providing them with better immune systems to fight infections."

Explore further: Scientists wage fight against aging bone marrow stem cell niche

More information: Theodore T. Ho et al. Autophagy maintains the metabolism and function of young and old stem cells, Nature (2017). DOI: 10.1038/nature21388

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A French teen who was given gene therapy for sickle cell disease more than two years ago now has enough properly working red blood cells to dodge the effects of the disorder, researchers report.

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Researchers find key to 'tired' blood and immune systems - Medical Xpress

The natural lifecycle of cells that line the intestine is critical to preserving stable conditions in the gut, according to new research led by a Weill Cornell Medicine investigator. The findings may lead to the development of new therapies to alleviate inflammatory bowel disease (IBD) and other chronic inflammatory illnesses.

In the study, published Nov. 9 in Nature, the scientists investigated the healthy turnover of epithelial cells, which are born and die every four to five days, to better understand how the gut maintains a healthy equilibrium. Because cells, called phagocytes, can clear dying cells so quickly in the body, it had been difficult to study this process in tissues. The inability to clear dying cells has been linked to inflammation and autoimmunity. Dying epithelial cells are shed into the gut lumen, so their active clearance is not necessary and they were thought to have no role in intestinal inflammation.

The investigators sought to understand whether phagocytes can take up dying epithelial cells in the gut and, if so, how these phagocytes respond. Specifically, the study tried to ascertain which genes are expressed by phagocytes after the uptake of dead cells. To answer these questions, the scientists engineered a mouse model where they could turn on apoptosis and catch phagocytes in the act of sampling dying cells. Through a series of experiments, they found that several of the genes modulated up or down in phagocytes bearing dead cells overlapped with the same genes that have been associated with susceptibility to IBD.

The mouse model used in the study enables the visualization of a dying red cell within the green fluorescently-labeled small intestinal epithelial cells. The green outline of villi shown delineates the single cell layer of the intestinal epithelium. Cell nuclei are shown in blue. Weill Cornell Medicine investigators tracked dying intestinal epithelial cells into the underlying phagocytes (not visible), and asked how their uptake modulates gene expression in those phagocytes.

The fact that there was an overlap shows that apoptosis must play a role in maintaining equilibrium in the gut, said Dr. Julie Magarian Blander, a senior faculty member in the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine who was recently recruited as a professor of immunology from Mount Sinai. This study identified cell death within the epithelium as an important factor to consider when thinking about therapeutic strategies for patients with IBD.

In their experiments, the scientists expressed a green fluorescent protein fused to the diphtheria toxin receptor within intestinal epithelial cells of mice, which made them visible under a microscope and sensitive to diphtheria toxin. They injected into these mice a carefully titrated dose of toxin into the intestinal walls of mice to induce cell death. Then the team examined the phagocytes that turned green after they internalized dead cells. Macrophages, one kind of phagocyte, expressed genes that help process the increased lipid and cholesterol load they acquired from dying cells. Dendritic cells, another type of phagocyte, activated genes responsible for instructing the development of regulatory CD4 T cells, a class of suppressive white blood cells. Notably, both phagocytes expressed a common suppression of inflammation gene signature.

Because the same genes that confer susceptibility to IBD were modulated in response to apoptotic cell sampling, the research indicates that a disruption of the phagocytes immunosuppressive response would have consequences for homeostasis or stable conditions in the gut.

We know there is excessive cell death, inflammation and microbial imbalance in IBD, so the prediction is that the immunosuppressive program in phagocytes, associated with natural cell death in the gut epithelium, would be disrupted, Dr. Blander said. The goal in the treatment of IBD is to enhance healing in the gut, but now we know that this also helps phagocytes restore their immunosuppressive and homeostatic functions. We think this would translate into helping patients stay in remission. Theres a lot to learn from phagocytes and we may be able to target the same pathways they use to suppress inflammation in patients with IBD.

The study validates the importance of healing in the mucosa, or lining, of the intestine as a therapy and enhances the understanding of that process. The next phase of Dr. Blanders research will be to investigate how the inflammatory conditions of IBD alter cell death and the homeostatic immunosuppressive functions of intestinal phagocytes, and to do so in both mouse models and different groups of IBD patients undergoing anti-TNF therapy at the Jill Roberts Center for Inflammatory Bowel Disease at New York-Presbyterian and Weill Cornell Medicine.

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