Category Archives: Cell Medicine

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

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

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

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

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

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

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

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

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

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

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

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

Adding just the right mixture of signaling moleculesproteins involved in developmentto human stem cells can coax them to resemble somites, which are groups of cells that give rise to skeletal muscles, bones, and cartilage ...

Researchers at the University of Maine MicroInstruments and Systems Laboratory (MISL), in collaboration with The Jackson Laboratory, have developed a new microfluidic tool that reproduces in the laboratory the same physiochemical ...

Cedars-Sinai scientists are seeking to build an improved stem-cell model of amyotrophic lateral sclerosis (ALS) to accelerate progress toward a cure for the devastating neurological disorder. Their findings demonstrate that ...

esearchers from Hokkaido University in Japan together with an international team of scientists implanted specialized embryonic stem cells into the severed spinal cords of rats. The stem cells, called neural progenitor cells, ...

Caltech scientists have converted cells of the lower-body region into facial tissue that makes cartilage, in new experiments using bird embryos. The researchers discovered a "gene circuit," composed of just three genes, that ...

New research has unravelled the mystery of how mitochondriathe energy generators within cellscan withstand attacks on their DNA from rogue molecules.

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

A gene previously identified as critical for tumor growth in many human cancers also maintains intestinal stem cells and encourages the growth of cells that support them, according to results of a study led by Johns Hopkins ...

A team of researchers at Sahlgrenska Academy has managed to generate cartilage tissue by printing stem cells using a 3-D-bioprinter. The fact that the stem cells survived being printed in this manner is a success in itself. ...

Using new gene-editing technology, researchers have rewired mouse stem cells to fight inflammation caused by arthritis and other chronic conditions. Such stem cells, known as SMART cells (Stem cells Modified for Autonomous ...

Researchers hope to one day use stem cells to heal burns, patch damaged heart tissue, even grow kidneys and other transplantable organs from scratch. This dream edges closer to reality every year, but one of the enduring ...

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New study reveals how embryonic cells make spinal cord, muscle and bone - Medical Xpress

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Goal is vaccine that targets inflammation in joints

Using CRISPR technology, a team of researchers led by Farshid Guilak, PhD, at Washington University School of Medicine in St. Louis, rewired stem cells' genetic circuits to produce an anti-inflammatory arthritis drug when the cells encounter inflammation. The technique eventually could act as a vaccine for arthritis and other chronic conditions.

Using new gene-editing technology, researchers have rewired mouse stem cells to fight inflammation caused by arthritis and other chronic conditions. Such stem cells, known as SMART cells (Stem cells Modified for Autonomous Regenerative Therapy),develop into cartilage cells that produce a biologic anti-inflammatory drug that, ideally, will replace arthritic cartilage and simultaneously protect joints and other tissues from damage that occurs with chronic inflammation.

The cells were developed at Washington University School of Medicine in St. Louis and Shriners Hospitals for Children-St. Louis, in collaboration with investigators at Duke University and Cytex Therapeutics Inc., both in Durham, N.C. The researchers initially worked with skin cells taken from the tails of mice and converted those cells into stem cells. Then, using the gene-editing tool CRISPR in cells grown in culture, they removed a key gene in the inflammatory process and replaced it with a gene that releases a biologic drug that combats inflammation.

The research is availableonline April 27 in the journal Stem Cell Reports.

Our goal is to package the rewired stem cells as a vaccine for arthritis, which would deliver an anti-inflammatory drug to an arthritic joint but only when it is needed, said Farshid Guilak, PhD, the papers senior author and a professor of orthopedic surgery at Washington University School of Medicine. To do this, we needed to create a smart cell.

Many current drugs used to treat arthritis including Enbrel, Humira and Remicade attack an inflammation-promoting molecule called tumor necrosis factor-alpha (TNF-alpha). But the problem with these drugs is that they are given systemically rather than targeted to joints. As a result, they interfere with the immune system throughout the body and can make patients susceptible to side effects such as infections.

We want to use our gene-editing technology as a way to deliver targeted therapy in response to localized inflammation in a joint, as opposed to current drug therapies that can interfere with the inflammatory response through the entire body, said Guilak, also a professor of developmental biology and of biomedical engineering and co-director of Washington Universitys Center of Regenerative Medicine. If this strategy proves to be successful, the engineered cells only would block inflammation when inflammatory signals are released, such as during an arthritic flare in that joint.

As part of the study, Guilak and his colleagues grew mouse stem cells in a test tube and then used CRISPR technology to replace a critical mediator of inflammation with a TNF-alpha inhibitor.

Exploiting tools from synthetic biology, we found we could re-code the program that stem cells use to orchestrate their response to inflammation, said Jonathan Brunger, PhD, the papers first author and a postdoctoral fellow in cellular and molecular pharmacology at the University of California, San Francisco.

Over the course of a few days, the team directed the modified stem cells to grow into cartilage cells and produce cartilage tissue. Further experiments by the team showed that the engineered cartilage was protected from inflammation.

We hijacked an inflammatory pathway to create cells that produced a protective drug, Brunger said.

The researchers also encoded the stem/cartilage cells with genes that made the cells light up when responding to inflammation, so the scientists easily could determine when the cells were responding. Recently, Guilaks team has begun testing the engineered stem cells in mouse models of rheumatoid arthritis and other inflammatory diseases.

If the work can be replicated in animals and then developed into a clinical therapy, the engineered cells or cartilage grown from stem cells would respond to inflammation by releasing a biologic drug the TNF-alpha inhibitor that would protect the synthetic cartilage cells that Guilaks team created and the natural cartilage cells in specific joints.

When these cells see TNF-alpha, they rapidly activate a therapy that reduces inflammation, Guilak explained. We believe this strategy also may work for other systems that depend on a feedback loop. In diabetes, for example, its possible we could make stem cells that would sense glucose and turn on insulin in response. We are using pluripotent stem cells, so we can make them into any cell type, and with CRISPR, we can remove or insert genes that have the potential to treat many types of disorders.

With an eye toward further applications of this approach, Brunger added, The ability to build living tissues from smart stem cells that precisely respond to their environment opens up exciting possibilities for investigation in regenerative medicine.

Brunger JM, Zutshi A, Willard VP, Gersbach CA, Guilak F. Genome engineering of stem cells for autonomously regulated, closed-loop delivery of biologic drugs. Stem Cell Reports. April 27, 2017.

This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute on Aging of the National Institutes of Health (NIH), grant numbers AR061042, AR50245, AR46652, AR48182, AR067467, AR065956, AG15768, OD008586. Additional funding provided by the Nancy Taylor Foundation for Chronic Diseases; the Arthritis Foundation; the National Science Foundation (NSF), CAREER award number CBET-1151035; and the Collaborative Research Center of the AO Foundation, Davos, Switzerland.

Authors Farshid Guilak, and Vincent Willard have a financial interest in Cytex Therapeutics of Durham, N.C., which may choose to license this technology. Cytex is a startup founded by some of the investigators. They could realize financial gain if the technology eventually is approved for clinical use.

Washington University School of Medicines 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked seventh in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Stem cells edited to fight arthritis - Washington University School of Medicine in St. Louis

LOS ANGELES, April 26, 2017 /PRNewswire/ --Capricor Therapeutics, Inc. (CAPR), a clinical-stage biotechnology company developing first-in-class biological therapies for cardiac and other medical conditions, today announced that Linda Marbn, Ph.D., president and chief executive officer, is scheduled to present at the Alliance for Regenerative Medicine's 5th Annual Cell & Gene Therapy Investor Day on April 27, 2017 at The State Room in Boston, Massachusetts. The presentation will begin at approximately 9:40 a.m. eastern time and a live webcast of the event will be available at http://www.arminvestorday.com/webcast/.

About Capricor Therapeutics

Capricor Therapeutics, Inc. (CAPR) is a clinical-stage biotechnology company developing first-in-class biological therapies for cardiac and other medical conditions. Capricor's lead candidate, CAP-1002, is a cell-based candidate currently in clinical development for the treatment of Duchenne muscular dystrophy, myocardial infarction (heart attack), and heart failure. Capricor is exploring the potential of CAP-2003, a cell-free, exosome-based candidate, to treat a variety of disorders. For more information, visit http://www.capricor.com.

Cautionary Note Regarding Forward-Looking Statements

Statements in this press release regarding the efficacy, safety, and intended utilization of Capricor's product candidates; the initiation, conduct, size, timing and results of discovery efforts and clinical trials; the pace of enrollment of clinical trials; plans regarding regulatory filings, future research and clinical trials; plans regarding current and future collaborative activities and the ownership of commercial rights; scope, duration, validity and enforceability of intellectual property rights; future royalty streams, expectations with respect to the expected use of proceeds from the recently completed offerings and the anticipated effects of the offerings, and any other statements about Capricor's management team's future expectations, beliefs, goals, plans or prospects constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Any statements that are not statements of historical fact (including statements containing the words "believes," "plans," "could," "anticipates," "expects," "estimates," "should," "target," "will," "would" and similar expressions) should also be considered to be forward-looking statements. There are a number of important factors that could cause actual results or events to differ materially from those indicated by such forward-looking statements. More information about these and other risks that may impact Capricor's business is set forth in Capricor's Annual Report on Form 10-K for the year ended December 31, 2016, as filed with the Securities and Exchange Commission on March 16, 2017, and in its Registration Statement on Form S-3, as filed with the Securities and Exchange Commission on September 28, 2015, together with prospectus supplements thereto. All forward-looking statements in this press release are based on information available to Capricor as of the date hereof, and Capricor assumes no obligation to update these forward-looking statements.

CAP-1002 is an Investigational New Drug and is not approved for any indications. Capricor's exosomes technology, including CAP-2003, has not yet been approved for clinical investigation.

For more information, please contact:

Corporate Capricor Therapeutics, Inc. AJ Bergmann, Vice President of Finance +1-310-358-3200 abergmann@capricor.com

Investor RelationsArgot Partners Kimberly Minarovich +1-212-600-1902 kimberly@argotpartners.com

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/capricor-therapeutics-to-present-at-the-alliance-for-regenerative-medicines-cell--gene-therapy-investor-day-300445808.html

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Capricor Therapeutics to Present at the Alliance for Regenerative Medicine's Cell & Gene Therapy Investor Day - Yahoo Finance

Photo by Hannah Robbins/HSCI

In a cross-school collaboration, Harvard researchers Steve McCarroll (left) and Kevin Eggan couple stem cell science with genetics and genomicsto advance the understanding of human brain illnesses. Their latest project identifiedmutations that stem cell lines acquire in culture.

Regenerative medicine using human pluripotent stem cells to grow transplantable tissue outside the body carries the promise to treat a range of intractable disorders, such as diabetes and Parkinsons disease.

However, a research team from the Harvard Stem Cell Institute (HSCI), Harvard Medical School (HMS), and the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard has found that as stem cell lines grow in a lab dish, they often acquire mutations in the TP53 (p53) gene, an important tumor suppressor responsible for controlling cell growth and division.

Their research suggests that genetic sequencing technologies should be used to screen for mutated cells in stem cell cultures, so that cultures with mutated cells can be excluded from scientific experiments and clinical therapies. If such methods are not employed it could lead to an elevated cancer risk in those receiving transplants.

The paper, published online today in the journal Nature, comes at just the right time, the researchers said, as experimental treatments using human pluripotent stem cells are ramping up across the country.

Our results underscore the need for the field of regenerative medicine to proceed with care, said the studys co-corresponding author Kevin Eggan, an HSCI principal faculty member and the director of stem cell biology for the Stanley Center. Eggans lab in Harvard Universitys Department of Stem Cell and Regenerative Biology uses human stem cells to study the mechanisms of brain disorders, including amyotrophic lateral sclerosis, intellectual disability, and schizophrenia.

The research, the team said, should not discourage the pursuit of experimental treatments but instead be heeded as a call to screen rigorously all cell lines for mutations at various stages of development as well as immediately before transplantation.

Our findings indicate that an additional series of quality control checks should be implemented during the production of stem cells and their downstream use in developing therapies, Eggan said. Fortunately, these genetic checks can be readily performed with precise, sensitive, and increasingly inexpensive sequencing methods.

With human stem cells, researchers can re-create human tissue in the lab. This enables them to study the mechanisms by which certain genes can predispose an individual to a particular disease. Eggan has been working with Steve McCarroll, associate professor of genetics at Harvard Medical School and director of genetics at the Stanley Center, to study how genes shape the biology of neurons, which can be derived from these stem cells.

McCarrolls lab recently discovered a common, precancerous condition in which a blood stem cell in the body acquires a pro-growth mutation and then outcompetes a persons normal stem cells, becoming the dominant generator of his or her blood cells. People in whom this condition has appeared are 12 times likelier to develop blood cancer later in life. The studys lead authors, Florian Merkle and Sulagna Ghosh, collaborated with Eggan and McCarroll to test whether laboratory-grown stem cells might be vulnerable to an analogous process.

Cells in the lab, like cells in the body, acquire mutations all the time, said McCarroll, co-corresponding author. Mutations in most genes have little impact on the larger tissue or cell line. But cells with a pro-growth mutation can outcompete other cells, become very numerous, and take over a tissue. We found that this process of clonal selection the basis of cancer formation in the body is also routinely happening in laboratories.

To find acquired mutations, the researchers performed genetic analyses on 140 stem cell lines 26 of which were developed for therapeutic purposes using Good Manufacturing Practices, a quality control standard set by regulatory agencies in multiple countries. The remaining 114 were listed on the National Institutes of Health registry of human pluripotent stem cells.

While we expected to find some mutations in stem cell lines, we were surprised to find that about 5 percent of the stem cell lines we analyzed had acquired mutations in a tumor-suppressing gene called p53, said Merkle.

Nicknamed the guardian of the genome, p53 controls cell growth and cell death. People who inherit p53 mutations develop a rare disorder called Li-Fraumeni Syndrome, which confers a near 100 percent risk of developing cancer in a wide range of tissue types.

The specific mutations that the researchers observed are dominant-negative mutations, meaning that when they are present on even one copy of p53, they are able to compromise the function of the normal protein, whose components are made from both gene copies. The exact same dominant-negative mutations are among the most commonly observed mutations in human cancers.

These precise mutations are very familiar to cancer scientists. They are among the worst p53 mutations to have, said Ghosh, a co-lead author of the study.

The researchers performed a sophisticated set of DNA analyses to rule out the possibility that these mutations had been inherited rather than acquired as the cells grew in the lab. In subsequent experiments, the Harvard scientists found that p53 mutant cells outperformed and outcompeted non-mutant cells in the lab dish. In other words, a culture with a million healthy cells and one p53 mutant cell, said Eggan, could quickly become a culture of only mutant cells.

The spectrum of tissues at risk for transformation when harboring a p53 mutation includes many of those that we would like to target for repair with regenerative medicine using human pluripotent stem cells, said Eggan. Those organs include the pancreas, brain, blood, bone, skin, liver, and lungs.

However, Eggan and McCarroll emphasized that now that this phenomenon has been found, inexpensive gene-sequencing tests will allow researchers to identify and remove from the production line cell cultures with worrisome mutations that might prove dangerous after transplantation.

The researchers point out in their paper that screening approaches to identify these p53 mutations and others that confer cancer risk already exist and are used in cancer diagnostics. In fact, in an ongoing clinical trial that is transplanting cells derived from induced pluripotent stem cells, gene sequencing is used to ensure the transplanted cell products are free of dangerous mutations.

This work was supported by the Harvard Stem Cell Institute, the Stanley Center for Psychiatric Research, the Rosetrees Trust, the Azrieli Foundation, Howard Hughes Medical Institute, the Wellcome Trust, the Medical Research Council, the Academy of Medical Sciences, and by grants from the NIH.

By Al Powell, Harvard Staff Writer | April 26, 2017

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Stem cell lines grown in lab dish may acquire mutations - Harvard Gazette

Regenerative medicine using human pluripotent stem cells to grow transplantable tissue outside the body carries the promise to treat a range of intractable disorders, such as diabetes and Parkinson's disease.

However, a research team from the Harvard Stem Cell Institute (HSCI), Harvard Medical School (HMS), and the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard has found that as stem cell lines grow in a lab dish, they often acquire mutations in the TP53 (p53) gene, an important tumor suppressor responsible for controlling cell growth and division.

Their research suggests that genetic sequencing technologies should be used to screen for mutated cells in stem cell cultures, so that cultures with mutated cells can be excluded from scientific experiments and clinical therapies. If such methods are not employed it could lead to an elevated cancer risk in those receiving transplants.

The paper, published online in the journal Nature on April, 26, comes at just the right time, the researchers said, as experimental treatments using human pluripotent stem cells are ramping up across the country.

"Our results underscore the need for the field of regenerative medicine to proceed with care," said the study's co-corresponding author Kevin Eggan, an HSCI Principal Faculty member and the director of stem cell biology for the Stanley Center. Eggan's lab in Harvard University's Department of Stem Cell and Regenerative Biology uses human stem cells to study the mechanisms of brain disorders, including amyotrophic lateral sclerosis, intellectual disability, and schizophrenia.

The research, the team said, should not discourage the pursuit of experimental treatments but instead be heeded as a call to screen rigorously all cell lines for mutations at various stages of development as well as immediately before transplantation.

"Our findings indicate that an additional series of quality control checks should be implemented during the production of stem cells and their downstream use in developing therapies," Eggan said. "Fortunately, these genetic checks can be readily performed with precise, sensitive, and increasingly inexpensive sequencing methods."

With human stem cells, researchers can recreate human tissue in the lab. This enables them to study the mechanisms by which certain genes can predispose an individual to a particular disease. Eggan has been working with Steve McCarroll, associate professor of genetics at Harvard Medical School and director of genetics at the Stanley Center, to study how genes shape the biology of neurons, which can be derived from these stem cells.

McCarroll's lab recently discovered a common, precancerous condition in which a blood stem cell in the body acquires a pro-growth mutation and then outcompetes a person's normal stem cells, becoming the dominant generator of his or her blood cells. People in whom this condition has appeared are 12 times more likely to develop blood cancer later in life. The study's lead authors, Florian Merkle and Sulagna Ghosh, collaborated with Eggan and McCarroll to test whether laboratory-grown stem cells might be vulnerable to an analogous process.

"Cells in the lab, like cells in the body, acquire mutations all the time," said McCarroll, co-corresponding author. "Mutations in most genes have little impact on the larger tissue or cell line. But cells with a pro-growth mutation can outcompete other cells, become very numerous, and 'take over' a tissue. We found that this process of clonal selection -- the basis of cancer formation in the body -- is also routinely happening in laboratories."

To find acquired mutations, the researchers performed genetic analyses on 140 stem cell lines -- 26 of which were developed for therapeutic purposes using Good Manufacturing Practices, a quality control standard set by regulatory agencies in multiple countries. The remaining 114 were listed on the NIH registry of human pluripotent stem cells.

"While we expected to find some mutations in stem cell lines, we were surprised to find that about five percent of the stem cell lines we analyzed had acquired mutations in a tumor-suppressing gene called p53," said Merkle.

Nicknamed the "guardian of the genome," p53 controls cell growth and cell death. People who inherit p53 mutations develop a rare disorder called Li-Fraumeni Syndrome, which confers a near 100 percent risk of developing cancer in a wide range of tissue types.

The specific mutations that the researchers observed are "dominant negative" mutations, meaning, when present on even one copy of P53, they are able to compromise the function of the normal protein, whose components are made from both gene copies. The exact same dominant-negative mutations are among the most commonly observed mutations in human cancers.

"These precise mutations are very familiar to cancer scientists. They are among the worst P53 mutations to have," said Sulagna Ghosh, a co-lead author of the study.

The researchers performed a sophisticated set of DNA analyses to rule out the possibility that these mutations had been inherited rather than acquired as the cells grew in the lab. In subsequent experiments, the Harvard scientists found that p53 mutant cells outperformed and outcompeted non-mutant cells in the lab dish. In other words, a culture with a million healthy cells and one p53 mutant cell, said Eggan, could quickly become a culture of only mutant cells.

"The spectrum of tissues at risk for transformation when harboring a p53 mutation include many of those that we would like to target for repair with regenerative medicine using human pluripotent stem cells," said Eggan. Those organs include the pancreas, brain, blood, bone, skin, liver and lungs.

However, Eggan and McCarroll emphasized that now that this phenomenon has been found, inexpensive gene-sequencing tests will allow researchers to identify and remove from the production line cell cultures with concerning mutations that might prove dangerous after transplantation.

The researchers point out in their paper that screening approaches to identify these p53 mutations and others that confer cancer risk already exist and are used in cancer diagnostics. In fact, in an ongoing clinical trial that is transplanting cells derived from induced pluripotent stem cells (iPSCs), gene sequencing is used to ensure the transplanted cell products are free of dangerous mutations.

Read more:
Genes need to be screened for stem cell transplants - Science Daily

Capricor Therapeutics, Inc. (NASDAQ: CAPR) is a clinical-stage biotechnology company developing first-in-class biological therapies for cardiac and other medical conditions. Capricor's lead candidate, CAP-1002, is a cell-based candidate currently in clinical development for the treatment of Duchenne muscular dystrophy, myocardial infarction (heart attack), and heart failure. Capricor is exploring the potential of CAP-2003, a cell-free, exosome-based candidate, to treat a variety of disorders. For more information, visit http://www.capricor.com.

Cautionary Note Regarding Forward-Looking Statements

Statements in this press release regarding the efficacy, safety, and intended utilization of Capricor's product candidates; the initiation, conduct, size, timing and results of discovery efforts and clinical trials; the pace of enrollment of clinical trials; plans regarding regulatory filings, future research and clinical trials; plans regarding current and future collaborative activities and the ownership of commercial rights; scope, duration, validity and enforceability of intellectual property rights; future royalty streams, expectations with respect to the expected use of proceeds from the recently completed offerings and the anticipated effects of the offerings, and any other statements about Capricor's management team's future expectations, beliefs, goals, plans or prospects constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Any statements that are not statements of historical fact (including statements containing the words "believes," "plans," "could," "anticipates," "expects," "estimates," "should," "target," "will," "would" and similar expressions) should also be considered to be forward-looking statements. There are a number of important factors that could cause actual results or events to differ materially from those indicated by such forward-looking statements. More information about these and other risks that may impact Capricor's business is set forth in Capricor's Annual Report on Form 10-K for the year ended December 31, 2016, as filed with the Securities and Exchange Commission on March 16, 2017, and in its Registration Statement on Form S-3, as filed with the Securities and Exchange Commission on September 28, 2015, together with prospectus supplements thereto. All forward-looking statements in this press release are based on information available to Capricor as of the date hereof, and Capricor assumes no obligation to update these forward-looking statements.

CAP-1002 is an Investigational New Drug and is not approved for any indications. Capricor's exosomes technology, including CAP-2003, has not yet been approved for clinical investigation.

For more information, please contact:

Corporate Capricor Therapeutics, Inc. AJ Bergmann, Vice President of Finance +1-310-358-3200 abergmann@capricor.com

Investor RelationsArgot Partners Kimberly Minarovich +1-212-600-1902 kimberly@argotpartners.com

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/capricor-therapeutics-to-present-at-the-alliance-for-regenerative-medicines-cell--gene-therapy-investor-day-300445808.html

SOURCE Capricor Therapeutics, Inc.

http://capricor.com

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Capricor Therapeutics to Present at the Alliance for Regenerative Medicine's Cell & Gene Therapy Investor Day - PR Newswire (press release)

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Dr. Murdoch is a stem cell biologist with an interest in development and regenerative medicine. After completing post-doctoral training at Yale University, she took the role of Assistant Professor at Eastern Connecticut State University, where her time is split between teaching and researching nervous system development.

As our understanding of stem cells has increased, the possibility of using stem cell therapies to treat disease is on the horizon. Barbara Murdoch, Ph.D., Assistant Professor at Eastern Connecticut State University, is studying stem cells found in the olfactory epithelium (OE) with the aim of finding therapies for neurodegeneration.

Exclusive neurogenic niche: The olfactory epithelium

The OE is one of the few tissues in the body which is known to regenerate neurons, preserving our sense of smell throughout our lives.

Have you ever had the experience where you smell something and the scent evokes a memory from years back in time? asked Dr. Murdoch. This is because not only can the stem cells in the OE divide and differentiate to replace the lost neurons, but they can also recreate the exact same connection in the brain as the neuron they are replacing.

Dr. Murdoch explained how by studying these stem cells, she hoped to elucidate the environment and signaling molecules which restrict them to certain cell fates. The aim of her research is to direct neural stem/progenitor cells to create neurons in vitro. We can transplant neuronal precursor cells which are on their way to make neurons into patients, for example to help them recover after a stroke, said Dr. Murdoch.

Development of the olfactory epithelium approaches

One approach to understanding what dictates cell fate is to investigate the regions enriched for progenitors and determine their local microenvironment. The communication signals forming the microenvironment can be used to drive the production of new neurons from neuronal precursors in vitro. To investigate olfactory development, Dr. Murdoch carries out confocal microscopy using antibodies against numerous cell markers such as nestin, 3-tubulin and GFAP.

I was at a meeting when, just by chance, I came across a representative from Covance (now BioLegend) who had an anti-nestin antibody and was kind enough to give me a sample. When I tried it, it was brilliant in the olfactory epithelium and the brain, said Dr. Murdoch.

Dr. Murdoch published her findings in the 2008 Journal of Neuroscience paper, demonstrating that there were stem cell-like cells in the embryonic OE which are very similar to neural cells in the brain known as radial glia cells. Radial glia are responsible for the production of most if not all neurons in the brain. Previously, it was thought that radial glia cells were restricted to the central nervous system, but Dr. Murdochs research shows that they are also present in the OE, which is part of the peripheral nervous system.

The reason I think this was missed by so many other researchers was that the antibody that was typically used as a marker of neural stem cells, the anti-nestin antibody, worked well in the brain but not very well in the OE, Dr. Murdoch explained. However, the new antibody from BioLegend was targeting a different epitope, allowing it to identify and bind well to nestin expressed in the OE.

Dr. Murdoch described finding effective primary antibodies as a somewhat hit or miss process. Often when Im searching for antibodies, I try to get a sample and test it with the organism and tissue type Im using. When you find antibodies that work, you stick with them. Thats the reason why I stick with the antibodies from BioLegend, as they are so specific time and time again, Dr. Murdoch added.

The image shows differentiation into neurons (green) and glia (red). Blue indicates cell nuclei. Provided by Dr. Murdoch.

Future research and application in regenerative medicine approaches

Now an Assistant Professor at Eastern Connecticut State University, Dr. Murdoch is furthering her research by using chick embryos as a model to study how the OE develops.

Were trying to find pockets of progenitor cells and learn what the environmental influences surrounding those cells are in vivo, Dr. Murdoch explained.

This research has implications for regenerative medicine, where the same signals found in vivo can be recreated in vitro to make new neurons from neural precursors, derived either from human embryonic or induced pluripotent stem cells. Future work will aim to construct 3D scaffolds combined with signaling molecules and matrices to affect cell fate, Dr. Murdoch said.

Research such as Dr. Murdochs is contributing to an improved understanding of the signaling cascades found in neurogenic niches. Understanding the factors which decide cell fate and coordinate the generation of complex tissue is an important step in developing stem cell therapies to treat neurodegenerative states, such as Parkinsons disease, traumatic brain injury and stroke.

Dr. Murdochs work is funded by the CSU-AAUP.

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Neurological Regenerative Medicine Unlocking the Potential of ... - SelectScience

Enlarge / Oh, there's that cure I was looking for.

Tried, true, and FDA-approved drugs for cancer and depressionalready in medicine cabinetsmay also be long-sought treatments for devastating brain diseases such as Alzheimers, Parkinsons, and other forms of dementia, according to a new study in Brain, a Journal of Neurology.

The research is still in early stages; it only involved mouse and cell experiments, which are frequently not predictive of how things will go in humans. Nevertheless, the preliminary findings are strong, and scientists are optimistic that the drugs couldone day help patients with progressive brain disease. Researchers are moving toward human trials. And this process would be streamlined because the drugs have already cleared safety tests. But even if the early findings hold up, it would still take years to reach patients.

In the preliminary tests, the two drugstrazodone hydrochloride, used to treat depression and anxiety, and dibenzoylmethane (DBM), effective against prostate and breast tumorscould shut down a devastating stress response in brain cells, known to be critical for the progression of brain diseases. The drugs both protected brain cells and restored memory in mice suffering from brain diseases.

"We're excited by the potential of these findings from this well-conducted and robust study, Doug Brown, of the Alzheimer's Society, told the BBC.

David Dexter, from Parkinson's UK, added that if these studies were replicated in human clinical trials, both trazodone and DBM could represent a major step forward.

For years, researchers have known that a stress response in cells, called unfolded protein response, or UPR, is involved in a bunch of neurodegenerative diseases. The response kicks in when theres a buildup of unfolded or misfolded proteins. Typically, protein chains are folded into specific 3D structures that are often critical for their function in the body. But this folding goes awry in some neurodegenerative conditions, such as prion diseases, Alzheimer's disease, Parkinson's disease, and other forms of dementia.

When this happens, UPR kicks in. It shuts down protein production, tries to junk the botched proteins, and gets protein production machinery back in order. If all goes well, the cell can resume normal protein production. But if it doesnt, UPR initiates apoptosis, aka cell suicide.

In neurodegenerative diseases, things dont go well; UPR is over-activated, and brain cells start dying off. Scientists know that hampering UPR can protect brain cells and restore memory in mice engineered to mimic having Alzheimer's disease. But so far, all the compounds found to knock back UPR were highly toxic or highly insoluble (they dont work as medicine).

For a drug discovery shortcut, researchers at the University of Cambridge wondered: do we already have drugs that can interfere with UPRbut just dont know it? They screened a library of 1,040 FDA-approved drugs to find out.

Because UPR is highly conserved across animals, the researchers could use worms to screen the drugs. They initially found 20 drugs that seemed to have UPR-dampening effects. Upon further testing, they whittled down the list to five, then to two.

In further cell experiments, both trazodone and DBM inhibited a specific step in UPR and restored protein production. In mice, the drugs traversed the blood-brain barrier. When the researchers infected mice with a prion disease, clinically relevant doses of either drug held back neurological symptoms, boosted survival, and substantially reduced loss of brain cells in most of the infected mice. In mice that modeled a type of dementia, called frontotemporal dementia, both drugs could rescue the rodents memory and restore protein synthesis in brain cells.

The two drugs were markedly neuroprotective, the authors conclude. These drugs therefore represent an important step forward in the pursuit of disease-modifying treatments for Alzheimers and related disorders.

Trazodone, the authors note, is even already approved for use in the elderly. Clinical trials are the next step.

Brain, 2017. DOI: 10.1093/brain/awx074 (About DOIs).

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Drugs already in medicine cabinets may fight dementia, early data suggests - Ars Technica

On Saturday evening I, along with millions of other people, watched the premiere of Auntie Oprahs film, The Immortal Life of Henrietta Lacks, on HBO. At the beginning of the film, I was nestled in my bed, eating a bowl of popcorn. I knew the premise of the movie and seriously, who doesnt love a good Oprah Winfrey performance (and let me just say, as usual, she delivered). But by the middle of the film, I was no longer lying comfortably, instead I was sitting upright, slightly teary-eyed...and by the end, there was popcorn on the floor and I was standing in front my television, gripping my remote tightly and shaking my head in disbelief. I immediately scrolled through Facebook to see if I was alone, and just as I imagined, I wasnt.

Several people with skin like mine who watched the film felt just like I did. Dont get me wrong, the movie was well done and the acting was superb, but it did something that I wasnt expecting. It evoked emotions that are still somewhat difficult for me to articulate. Simply put, I hurt for Henrietta Lacks and her family.

As I watched the movie, I thought to myself, why didnt I learn more about Henny (Henny because shes now my auntie in my head) in school? From grades 7-12, I attended a health sciences magnet school. In college, I was a biology major. To say I know a little something about HeLa is an understatement, but I honestly dont recall hearing much about the owner of those magical cells. Yes, magical. Black girl magic isnt just a hashtag, you know. But I digress. Like many Black women, Henrietta Lacks was an unknown hero who, thanks to the book and subsequent film about her life, is no longer an obscure entity. However, unlike the three heroines in one of my favorite movies, Hidden Figures, Henriettas story did not have such a happy ending.

Henrietta was diagnosed with cervical cancer and died from the disease at the age of 31. As a result, she left a special legacy and five children whose lives would never be the same. But it wasnt her untimely death that shocked me as that was quite common back in the day. No, it was the blatant disregard for her basic human rights that I found so appalling. To which human right am I referring? Henrietta was not given the right to consent, and even though it was not required at that time, ethically, she should have been asked for the use of her cells.

Picture this. Youre a young woman, lying in a hospital bed, gravely ill and undergoing treatment for a disease you dont fully understand. There are doctors and nurses coming in and out of your room. They are talking to you, smiling at you, and poking you with needles. They spread your legs to take a piece of your cervix so they can figure out how to fix you. Its ok because you trust them. But not one time do they ask you if they can use the cells from your body to learn more about your disease. No one takes the time to explain to you how the use of your cells could possibly benefit others for years to come. And after you pass away, no one consults your grieving family members to obtain permission to continue the use of your cells.

Mrs. Lacks, we need your permission for something. Can we use the cells from your biopsy for research? Theres a possibility that you could help us understand this disease better. You could also be helping others.

I imagine a conversation like that with Henrietta would have sufficed, but that didnt happen. So lets not sugarcoat it. Henriettas cells were stolen. Her cells were taken and used to advance research and medical practices and she went virtually unknown for years. And to make matters worse, her family still has not been properly compensated. Unbelievable, I know. Now, some may wonder whats so great about Henriettas cells anyway. Why does her family deserve anything after all of this time? Well, let me explain.

Henrietta cells, i.e., HeLa, were unique. You may say she was an ordinary woman with extraordinary cells. HeLa cells are an immortalized cell line, meaning the cells can be reproduced infinitely in a lab. Her cells have aided in the advancement of science and modern medicine tremendously. For example, the cells were used to develop the polio vaccine. In addition, they have been instrumental in HIV and cancer research. Oh, but it doesnt stop there. These cells even paved the way for in vitro fertilization, and the list goes on and on. And while I am thankful for the progress Henriettas cells have afforded medical research, the treatment of Blacks as guinea pigs in the past has left a very bitter taste in my mouth.

Real talk. What occurred to Henrietta wasnt an isolated incident. We all know about the Tuskegee Experiment the time scientists used Black men as lab animals to study the effects of Syphilis but I wonder just how many stories like Henriettas and the Tuskegee Experiment are still untold? And why have the contributions of so many Blacks been undervalued or erased from the history books? And lastly, why is health equity still so difficult to attain in 2017. What do I mean by that last question? Well, for example, Black women are still dying from breast and cervical cancers at higher rates than other ethnic/racial groups. The same goes for Black men and prostate cancer. I could go on but you get the point. The fact is, I dont know the answers to these questions, and as a public health professional, I am working everyday to identify solutions. But what I do know is this, modern medicine has a huge unpaid debt. The creditors are the descendants of Mrs. Henrietta Lacks, and I, for one, think its time to pay up.

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Henrietta Lacks And Modern Medicine's Greatest Unpaid Debt - Huffington Post

Fort Lauderdale, FL Life Extension has partnered with Insilico Medicine to introduce Ageless Cell, the first supplement in its GEROPROTECT line to promote healthy aging by inhibiting cellular senescence.

Cellular senescence is a natural part of the aging process where cells no longer function optimally, affecting organ function, cellular metabolism, and inflammatory response. The accumulation of these senescent cells contributes to the process of aging. The Ageless Cell supplements inhibit the effects of cellular senescence by acting as geroprotectors, or interventions aimed to increase longevity and impede the onset of age-related diseases by targeting and inhibiting senescence-inducing pathways and inhibiting the development of senescent cells.

The partnership with Insilico Medicine allowed researchers to use deep learning algorithms to comb through hundreds of studies and thousands of data points a process that could have taken decades to identify four key anti-aging nutrients: N-Acetyl-L-Cysteine (NAC), myricetin, gamma-tocotrienol, and EGCG. These compounds target pathways that are known to contribute to or protect against the development of senescent cells.

Specifically, NAC upregulates signaling pathways that protect cells against oxidative stress, which promotes cellular senescence. It also reduces pathways that promote inflammation. Myricetin regulates a family of stress-responsive signaling molecules known to regulate aging in many tissues. It also promotes cell differentiation and self-repair. Gamma tocotrienol modulates the mevalonate pathway that controls cholesterol production, cancer promotion, and bone formation. And EGCG regulates the Wnt pathway that determines the fate of developing cells and also prevents sugar-induced damage to tissues, helping to suppress their pro-aging effects.

Clinical aging studies are extremely difficult, if not impossible, to perform at this time. Our collaboration with Insilico Medicine has allowed us to develop geroprotective formulations by using artificial intelligence to study very large data sets, said Andrew G. Swick, Ph.D., senior vice president of product development and scientific affairs for Life Extension.

Scientists found these four nutrients have various complementary and reinforcing properties to influence key anti-aging pathways and combat aging factors by modulating specific biological pathways. By rejuvenating near-senescent cells and encouraging the bodys healthy process for dealing with senescent cells, Ageless Cell turns back the clock at the cellular level, said Michael A. Smith, M.D., senior health scientist for Life Extension. Alex Zhavoronkov, Ph.D., CEO of Insilico Medicine said, Together, these four natural compounds represent the beginning of the future anti-aging cocktails identified using artificial intelligence under expert human supervision.

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Life Extension and Insilico Medicine Use AI to Develop Ageless Cell - WholeFoods Magazine