Monthly Archives: March 2017

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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Cell Death in Gut Implicated in IBD | Newsroom | Weill Cornell ... - Cornell Chronicle

March 1, 2017 by Marilynn Marchione This 2009 colorized microscope image made available by the Sickle Cell Foundation of Georgia via the Centers for Disease Control and Prevention shows a sickle cell, left, and normal red blood cells of a patient with sickle cell anemia. Researchers say 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. The case is detailed in the March 2, 2017 issue of the New England Journal of Medicine. (Janice Haney Carr/CDC/Sickle Cell Foundation of Georgia via AP)

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.

The first-in-the-world case is detailed in Thursday's New England Journal of Medicine.

About 90,000 people in the U.S., mostly blacks, have sickle cell, the first disease for which a molecular cause was found. Worldwide, about 275,000 babies are born with it each year.

"Vexing questions of race and stigma have shadowed the history of its medical treatment," including a time when blacks who carry the bad gene were urged not to have children, spurring accusations of genocide, Keith Wailoo of Princeton University wrote in a separate article in the journal.

The disease is caused by a single typo in the DNA alphabet of the gene for hemoglobin, the stuff in red blood cells that carries oxygen. When it's defective, the cells sickle into a crescent shape, clogging tiny blood vessels and causing bouts of extreme pain and sometimes more serious problems such as strokes and organ damage. It keeps many people from playing sports and enjoying other activities of normal life.

A stem cell transplant from a blood-matched sibling is a potential cure, but in the U.S., fewer than one in five people have a donor like that. Pain crises are treated with blood transfusions and drugs, but they're a temporary fix. Gene therapy offers hope of a lasting one.

The boy, now 15, was treated at Necker Children's Hospital in Paris in October 2014. Researchers gave him a gene, taken up by his blood stem cells, to help prevent the sickling. Now, about half of his red blood cells have normal hemoglobin; he has not needed a transfusion since three months after his treatment and is off all medicines.

"It's not a cure but it doesn't matter," because the disease is effectively dodged, said Philippe Leboulch, who helped invent the therapy and helped found Bluebird Bio in Cambridge, Massachusetts, the company that treated the boy. The work was supported by a grant from the French government's research agency.

Bluebird has treated at least six others in the U.S. and France. Full results have not been reported, but the gene therapy has not taken hold as well in some of them as it did in the French teen. Researchers think they know why and are adjusting methods to try to do better.

Two other gene therapy studies for sickle cell are underway in the U.S.at the University of California, Los Angeles and Cincinnati Children's Hospitaland another is about to start at Harvard and Boston Children's Hospital using a little different approach.

"This work gives considerable promise" for a solution to a very common problem, said Dr. Stuart Orkin, a Boston Children's Hospital doctor who is an inventor on a patent related to gene editing.

"The results are quite good in this patient," he said of the French teen. "It shows gene therapy is on the right track."

Explore further: BCL11A-based gene therapy for sickle cell disease passes key preclinical test

More information: Gene therapy: ghr.nlm.nih.gov/primer/therapy/availability

2017 The Associated Press. All rights reserved.

A precision-engineered gene therapy virus, inserted into blood stem cells that are then transplanted, markedly reduced sickle-induced red-cell damage in mice with sickle cell disease, researchers from Dana-Farber/Boston Children's ...

Sickle cell disease and the blood disorder beta thalassemia affect more than 180,000 Americans and millions more worldwide. Both diseases can be made milder or even cured by increasing fetal hemoglobin (HbF) levels, but current ...

Scientists at the Center for Regenerative Medicine (CReM) at Boston Medical Center (BMC) and Boston University School of Medicine (BUSM) are creating an induced pluripotent stem cell (iPSC)-based research library that opens ...

UCLA stem cell researchers have shown that a novel stem cell gene therapy method could lead to a one-time, lasting treatment for sickle cell diseasethe nation's most common inherited blood disorder.

A team of researchers at the Stanford University School of Medicine has used a gene-editing tool known as CRISPR to repair the gene that causes sickle cell disease in human stem cells, which they say is a key step toward ...

Scientists have developed a new approach to repair a defective gene in blood-forming stem cells from patients with a rare genetic immunodeficiency disorder called X-linked chronic granulomatous disease (X-CGD). After transplant ...

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.

A research team, led by the University of Minnesota, has discovered a groundbreaking process to successfully rewarm large-scale animal heart valves and blood vessels preserved at very low temperatures. The discovery is a ...

Working with yeast and human cells, researchers at Johns Hopkins say they have discovered an unexpected route for cells to eliminate protein clumps that may sometimes be the molecular equivalent of throwing too much or the ...

By changing one small portion of a stimulus that influences part of one molecule's function, engineers and researchers at Washington University in St. Louis have opened the door for more insight into how the molecule is associated ...

A minimally invasive, fiber-optic technique that accurately measures the passive stretch and twitch contraction of living muscle tissue could someday be an alternative to the painful muscle biopsies used to diagnose and treat ...

An in-depth computational analysis of genetic variants implicated in both schizophrenia and rheumatoid arthritis by researchers at the University of Pittsburgh points to eight genes that may explain why susceptibility to ...

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Gene therapy lets a French teen dodge sickle cell disease - Medical Xpress

Regenestem, LLC (http://www.regenestem.com), a U.S.-based medical practice company that focuses on adult stem cell treatments for patients around the world as well as physician training on the latest technologies, is pleased to announce that for the second straight year it will be hosting a conference on regenerative medicine on the island of Cuba. The 2017 Inter American Regenerative and Cellular Medicine Conference (http://www.regenestemconference.com) will be held October 25-27, in Havana.

Miami, Florida (PRWEB) March 01, 2017

Coming off the success of its inaugural conference on regenerative medicine held in Cuba last October, the American company Regenestem (http://www.regenestem.com) has announced that it will host the second such event later this year. The company looks to continue the scientific collaboration that took place at last year's conference between medical professionals from the U.S., Cuba and around the world.

Regenestem, an international medical practice firm based in South Florida and focused on adult stem cell therapies and physician training, will present the Second Inter American Regenerative and Cellular Medicine Conference, October 25-27, at the Palacio de Convenciones, in Havana. The event is held in association with the Cuban Institute of Hematology.

"Our first regenerative medicine conference in Cuba was such a tremendous success that as it was winding down, we knew we had to continue the momentum and hold the second conference in 2017," said Ricardo De Cubas, conference organizer and CEO of Regenestem. "International research initiatives must start with face-to-face interactions between physicians from various countries. This event successfully brings together clinician-researchers worldwide who all have a focus in regenerative medicine, while at the same time enhancing the scientific collaboration specifically between the U.S. and Cuba."

In October 2016, more than 180 physicians and other medical professionals from 14 countries attended the first annual conference on regenerative medicine.

The three-day event explores adult stem cell therapies as a standard form of medical treatment. The program also addresses specific issues involving the process of replacing, reengineering or regenerating human cells, tissues and organs to restore or establish a body's normal function.

Along with the presentations and discussions, the conference also provides a series of hands-on training workshops that focus on the procedures for conducting many of the more popular adult stem cell therapies.

Those physicians already confirmed as conference speakers for the second year are:

For more information or to register for the conference, go to http://www.regenestemconference.com or call (305) 224-1858.

About Regenestem, LLC

Regenestem (http://www.regenestem.com) is an international medical practice company focused on providing comprehensive solutions involving adult stem cell treatments and research. The company has assembled a talented staff of medical specialists - professionals trained in the latest cutting-edge procedures and protocols in cellular medicine. Regenestem is certified for the medical tourism market, and staff physicians are board-certified or board-eligible, providing services in more than 10 specialties. Regenestem investigates, shares, utilizes and integrates the latest protocols in the adult stem cell arena to deliver the best medical solutions to its patients. The brand includes a membership association of regenerative medicine clinics, a training and education division, and an online store.

Recently, Regenestem received approval for an information page at Wikipedia, the free online encyclopedia, at https://en.wikipedia.org/wiki/Regenestem.

For the original version on PRWeb visit: http://www.prweb.com/releases/2017/03/prweb14113450.htm

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Regenestem, LLC to Host 2nd Annual Inter American Regenerative and Cellular Medicine Conference in Cuba - Benzinga

SAN CARLOS, Calif. & BALTIMORE--(BUSINESS WIRE)--Johns Hopkins Medicine, the Maryland Stem Cell Research Fund (MSCRF) and BioCardia, Inc. (OTC:BCDA) today announced that the first patient has been treated in the pivotal Phase III CardiAMP clinical trial of a cell-based therapy for the treatment of ischemic heart failure that develops after a heart attack. The first patient was treated at Johns Hopkins Hospital by a team led by Peter Johnston, MD, a faculty member in the Department of Medicine and Division of Cardiology, and principal investigator of the trial at Johns Hopkins.

The investigational CardiAMP therapy is designed to deliver a high dose of a patients own bone marrow cells directly to the point of cardiac dysfunction, potentially stimulating the bodys natural healing mechanism after a heart attack.

The patient experience with CardiAMP therapy begins with a pre-procedural cell potency screening test. If a patient qualifies for therapy, they are scheduled for a bone marrow aspiration. A point of care cell processing platform is then utilized to concentrate the autologous bone marrow cells, which are subsequently delivered in a minimally-invasive procedure directly to the damaged regions in a patients heart.

This cell-based therapy offers great potential for heart failure patients, said Carl Pepine, MD, professor and former chief of cardiovascular medicine at the University of Florida, Gainesville and national co-principal investigator of the CardiAMP trial. We look forward to validating the impact of the therapy on patients quality of life and functional capacity in this important study.

In addition to Dr. Johnston, the CardiAMP research team at Johns Hopkins includes Gary Gerstenblith, MD, Jeffrey Brinker, MD, Ivan Borrello, MD, Judi Willhide, Katherine Laws, Audrey Dudek, Michele Fisher and John Texter, as well as the nurses and technicians of the Johns Hopkins Cardiovascular Interventional Laboratory.

Funding the clinical trial of this cell therapy, which could be the first cardiac cell therapy approved in the United States, is an important step towards treatments, said Dan Gincel, PhD., executive director of the MSCRF at TEDCO. Through our clinical program, we are advancing cures and improving healthcare in the State of Maryland.

The CardiAMP Heart Failure Trial is a phase III, multi-center, randomized, double-blinded, sham-controlled study of up to 260 patients at up to 40 centers nationwide, which includes an optional 10-patient roll-in cohort. The primary endpoint for the trial is a significant improvement in Six Minute Walk distance at 12 months post-treatment. Study subjects must be diagnosed with New York Heart Association (NYHA) Class II or III heart failure as a result of a previous heart attack. The national co-principal investigators are Dr. Pepine and Amish Raval, MD, of the University of Wisconsin.

For information about eligibility or enrollment in the trial, please visit http://www.clinicaltrials.gov or ask your cardiologist.

About BioCardia BioCardia, Inc., headquartered in San Carlos, CA, is developing regenerative biologic therapies to treat cardiovascular disease. CardiAMP and CardiALLO cell therapies are the companys biotherapeutic product candidates in clinical development. For more information, visit http://www.BioCardia.com.

About Johns Hopkins Medicine Johns Hopkins Medicine (JHM), headquartered in Baltimore, Maryland, is one of the leading health care systems in the United States. Johns Hopkins Medicine unites physicians and scientists of the Johns Hopkins University School of Medicine with the organizations, health professionals and facilities of The Johns Hopkins Hospital and Health System. For more information, visit http://www.hopkinsmedicine.org.

About Maryland Stem Cell Research Fund The Maryland Stem Cell Research Act of 2006was established by the Governor and the Maryland General Assembly during the 2006 legislative session and created the Maryland Stem Cell Research Fund. This fund is continued through an appropriation in the Governor's annual budget. The purpose of the Fund is to promote state-funded stem cell research and cures through grants and loans to public and private entities in the State. For more information, visit http://www.MSCRF.org.

Forward Looking Statements This press release contains forward-looking statements as that term is defined under the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, among other things, references to the enrollment of our Phase 3 trial, commercialization and efficacy of our products and therapies, the product development timelines of our competitors. Actual results could differ from those projected in any forward-looking statements due to numerous factors. Such factors include, among others, the inherent uncertainties associated with developing new products or technologies, unexpected expenditures, the ability to raise the additional funding needed to continue to pursue BioCardias business and product development plans, competition in the industry in which BioCardia operates and overall market conditions, and whether the combined funds will support BioCardias operations and enable BioCardia to advance its pivotal Phase 3 CardiAMP cell therapy program. These forward-looking statements are made as of the date of this press release, and BioCardia assumes no obligation to update the forward-looking statements.

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Johns Hopkins Medicine, Maryland Stem Cell Research Fund and ... - Business Wire (press release)

March 1, 2017 Mitochondria (red) that have imported misfolded proteins (green). Credit: Erli Jin and Linhao Ruan/Johns Hopkins Medicine

Working with yeast and human cells, researchers at Johns Hopkins say they have discovered an unexpected route for cells to eliminate protein clumps that may sometimes be the molecular equivalent of throwing too much or the wrong trash into the garbage disposal. Their finding, they say, could help explain part of what goes awry in the progression of such neurodegenerative diseases as Parkinson's and Alzheimer's.

Proteins in the cell that are damaged or folded incorrectly tend to form clumps or aggregates, which have been thought to dissolve gradually in a cell's cytoplasm or nucleus thanks to an enzyme complex called the proteasome, or in a digestive organelle called the lysosome.

But in experiments on yeast, which has many structures similar to those in human cells, the Johns Hopkins scientists unexpectedly found that many of those protein clumps break down in the cell's energy-producing powerhouses, called mitochondria. They also found that too many misfolded proteins can clog up and damage this vital structure.

The team's findings, described March 1 in Nature, could help explain why protein clumping and mitochondrial deterioration are both hallmarks of neurodegenerative diseases.

Rong Li, Ph.D., professor of cell biology, biomedical engineering and oncology at the Johns Hopkins University School of Medicine and a member of the Johns Hopkins Kimmel Cancer Center, who led the study, likens the disposal system to the interplay between a household's trash and a garbage disposal in the kitchen sink. The disposal is handy and helps keep the house free of food scraps, but the danger is that with too much trash, especially tough-to-grind garbage, the system could get clogged up or break down.

In a previous study, Li and her team found protein aggregates, which form abundantly under stressful conditions, such as intense heat, stuck to the outer surface of mitochondria. In this study, they found the aggregates bind to proteins that form the pores mitochondria normally use to import proteins needed to build this organelle. If these pores are damaged by mutations, then aggregates cannot be dissolved, the researchers report. These observations led the team to hypothesize that misfolded proteins in the aggregates are pulled into mitochondria for disposal, much like food scraps dropped into the garbage disposal. Testing this hypothesis was tricky, Li says, because most of the misfolded proteins started out in the cytoplasm, and most of those that enter mitochondria quickly get ground up.

As a consequence, Li and her team used a technique in which a fluorescent protein was split into two parts. Then, they put one part inside the mitochondria and linked the other part with a misfolded and clumping protein in the cytoplasm. If the misfolded protein entered the mitochondria, the two parts of the fluorescent protein could come together and light up the mitochondria. This was indeed what happened.

"With any experiment," Li says, "you have a hypothesis, but in your head, you may be skeptical, so seeing the bright mitochondria was an enlightening moment."

To see what might happen in a diseased system, the team then put into yeast cells a protein implicated in the neurodegenerative disease known as amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease. After a heat treatment that caused the ALS protein to misfold, it also wound up in the mitochondria. The researchers then did an experiment in which a lot of proteins in the cytoplasm were made to misfold and found that when too much of these proteins entered mitochondria, they started to break down.

The team wanted to make sure that the phenomenon it had observed in the yeast cells could also happen in human cells, so the scientists used the same split-fluorescent protein method to observe misfolded proteins to enter the mitochondria of lab-grown human retinal pigmented epithelial cells. As observed in yeast, misfolded proteins, but not those that were properly folded, entered and lit up mitochondria.

Biological systems are in general quite robust, but there are also some Achilles' heels that may be disease prone, Li says, and relying on the mitochondrial system to help with cleanup may be one such example. While young and healthy mitochondria may be fully up to the task, aged mitochondria or those overwhelmed by too much cleanup in troubled cells may suffer damage, which could then impair many of their other vital functions.

Explore further: Cell disposal faults could contribute to Parkinson's, study finds

More information: Linhao Ruan et al, Cytosolic proteostasis through importing of misfolded proteins into mitochondria, Nature (2017). DOI: 10.1038/nature21695

A fault with the natural waste disposal system that helps to keep our brain cell 'batteries' healthy may contribute to neurodegenerative disease, a new study has found.

To stay healthy, neurons must prevent protein aggregates and defective organelles such as mitochondria from accumulating inside them. We now know that an animal species has found a solution to its neuronal trash problemone ...

Scientists at the Stowers Institute for Medical Research have made a surprising finding about the aggregates of misfolded cellular proteins that have been linked to aging-related disorders such as Parkinson's disease. The ...

A new University of Colorado Boulder study shows for the first time the final stages of how mitochondria, the sausage-shaped, power-generating organelles found in nearly all living cells, regularly divide and propagate.

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.

A research team, led by the University of Minnesota, has discovered a groundbreaking process to successfully rewarm large-scale animal heart valves and blood vessels preserved at very low temperatures. The discovery is a ...

Working with yeast and human cells, researchers at Johns Hopkins say they have discovered an unexpected route for cells to eliminate protein clumps that may sometimes be the molecular equivalent of throwing too much or the ...

By changing one small portion of a stimulus that influences part of one molecule's function, engineers and researchers at Washington University in St. Louis have opened the door for more insight into how the molecule is associated ...

A minimally invasive, fiber-optic technique that accurately measures the passive stretch and twitch contraction of living muscle tissue could someday be an alternative to the painful muscle biopsies used to diagnose and treat ...

An in-depth computational analysis of genetic variants implicated in both schizophrenia and rheumatoid arthritis by researchers at the University of Pittsburgh points to eight genes that may explain why susceptibility to ...

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In cleaning up misfolded proteins, cell powerhouses can break down - Medical Xpress