Stem cell study points to cardiac treatment

SAN FRANCISCO — A UCSF stem cell study conducted in mice suggests a novel strategy for treating damaged cardiac tissue in patients following a heart attack. The approach potentially could improve cardiac function, minimize scar size, lead to the development of new blood vessels – and avoid the risk of tissue rejection.

In the investigation, reported online in the journal PLoS ONE, UCSF researchers isolated and characterized a novel type of cardiac stem cell from the heart tissue of middle-aged mice following a heart attack.

Then, in one experiment, they placed the cells in the culture dish and showed they had the ability to differentiate into cardiomyocytes, or “beating heart cells,” as well as endothelial cells and smooth muscle cells, all of which make up the heart.

In another, they made copies, or “clones,” of the cells and engrafted them in the tissue of other mice of the same genetic background who also had experienced heart attacks. The cells induced angiogenesis, or blood vessel growth, or differentiated, or specialized, into endothelial and smooth muscle cells, improving cardiac function.  

“These findings are very exciting,” said first author Jianqin Ye, Ph.D., M.D., senior scientist at UCSF’s Translational Cardiac Stem Cell Program. First, “we showed that we can isolate these cells from the heart of middle-aged animals, even after a heart attack.” Second, he said, “we determined that we can return these cells to the animals to induce repair.”

Importantly, the stem cells were identified and isolated in all four chambers of the heart, potentially making it possible to isolate them from patients’ hearts by doing right ventricular biopsies, said Ye. This procedure is “the safest way of obtaining cells from the heart of live patients, and is relatively easy to perform,” he said.

“The finding extends the current knowledge in the field of native cardiac progenitor cell therapy,” said senior author Yerem Yeghiazarians, M.D., director of UCSF’s Translational Cardiac Stem Cell Program and an associate professor at the UCSF Division of Cardiology. “Most of the previous research has focused on a different subset of cardiac progenitor cells. These novel cardiac precursor cells appear to have great therapeutic potential.”

The hope, he said, is that patients who have severe heart failure after a heart attack or have cardiomyopathy would be able to be treated with their own cardiac stem cells to improve the overall health and function of the heart. Because the cells would have come from the patients, themselves, there would be no concern of cell rejection after therapy.

The cells, known as Sca-1+ stem enriched in Islet (Isl-1) expressing cardiac precursors, play a major role in cardiac development. Until now, most of the research has focused on a different subset of cardiac progenitor, or early stage, cells known as, c-kit cells.

The Sca-1+ cells, like the c-kit cells, are located within a larger clump of cells called cardiospheres.

The UCSF researchers used special culture techniques and isolated Sca-1+ cells enriched in the Isl-1expressing cells, which are believed to be instrumental in the heart’s development. Since Isl-1 is expressed in the cell nucleus, it has been difficult to isolate them but the new technique enriches for this cell population.

The findings suggest a potential treatment strategy, said Yeghiazarians. “Heart disease, including heart attack and heart failure, is the number one killer in advanced countries. It would be a huge advance if we could decrease repeat hospitalizations, improve the quality of life and increase survival.” More studies are being planned to address these issues in the future.

An estimated 785,000 Americans will have a new heart attack this year, and 470,000 who will have a recurrent attack. Heart disease remains the number one killer in the United States, accounting for one out of every three deaths, according to the American Heart Association.

Medical costs of cardiovascular disease are projected to triple from $272.5 billion to $818.1 billion between now and 2030, according to a report published in the journal Circulation.

First author Ye, Henry Shih, Richard E. Sievers, Yan Zhang, and Megha Prasad are with the UCSF Division of Cardiology; Yeghiazarians and Andrew Boyle are with the UCSF Division of Cardiology and the UCSF Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research; William Grossman is with the UCSF Division of Cardiology and the UCSF Cardiovascular Research Institute; Harold S. Bernstein is with the UCSF Cardiovascular Research Institute, the UCSF Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, and the UCSF Department of Pediatrics; Hua Su is with UCSF Department of Anesthesia and Perioperative Care; and Yan Zhou with the UCSF Department of Cell and Tissue Biology.

The study was supported by funds from the Wayne and Gladys Valley Foundation, the UCSF Cardiac Stem Cell Fund and the Harold Castle Foundation.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

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Stem cell study points to cardiac treatment

Stem Cell Research Heals Scarring from Heart Attacks

Infusing stem cells into the arteries of heart attack patients can heal damaging scars, according to new research, a feat previously thought impossible.

Stem cells - cells that form different tissue of in the body - helped half of tested heart attack patients recover from their scars over a six-month period, according to the study. The control group did not see any additional recovery in their hearts.

The researchers recommended the experimental therapy expand into clinical trials beyond the 17 patients who received the original treatment.

"This has never been accomplished before, despite a decade of cell therapy trials for patients with heart attacks. Now we have done it," Eduardo Marban, director of the Cedars-Sinai Heart Institute and one of the study's co-authors, said in a statement. "The effects are substantial."

The research included a group of 25 patients who had suffered from heart attacks caused by a blockage in an artery. The online version of The Lancet published the research on Valentine's Day.

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The year-long study tested the effects of the stem cells on 17 patients, compared to eight control patients who received standard treatments of medication along with diet and exercise recommendations.

For each test patient, clinicians created a stock of stem cells from a heart sample smaller than a raisin. The researchers then injected the stem cells back into an artery damaged from the heart attack.

The authors reported no deaths or major side effects in either group. However, four patients in the stem cell group showed adverse reactions to the treatment whereas only one control showed complications. Adverse reactions included problems that required implantation of a defibrillator, according to the study.

"These results signal an approaching paradigm shift in the care of heart attack patients," Shlomo Melmed, dean of the Cedars-Sinai Heart Institute and a study co-author, said in a statement. "In the past, all we could do was to try to minimize heart damage by promptly opening up an occluded artery. Now, this study shows there is a regenerative therapy that may actually reverse the damage caused by a heart attack."

Other doctors expressed cautious optimism based on the results of the trial therapy.

"By preventing the consequences of a heart attack you may be able to prevent further down the heart failure that happens in [many of these] patients," Dr. Sonia Skarlatos, deputy director of the division of cardiovascular sciences at the NIH's National Heart, Lung, and Blood Institute, told CNN.

The researchers from the Cedars-Sinai Heart Institute initially set out to determine if the use of stem cells in heart attack patients was safe, and said they were surprised and excited to see the reduction in heart scarring and increase in healthy muscle tissue.

Marbán said the study will revolutionize how heart attacks are treated. "This discovery challenges the conventional wisdom that, once established, scar is permanent and that, once lost, healthy heart muscle cannot be restored."

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Stem Cell Research Heals Scarring from Heart Attacks

Stem Cell Study in Mice Offers Hope for Treating Heart Attack Patients

Newswise — A UCSF stem cell study conducted in mice suggests a novel strategy for treating damaged cardiac tissue in patients following a heart attack. The approach potentially could improve cardiac function, minimize scar size, lead to the development of new blood vessels – and avoid the risk of tissue rejection.

In the investigation, reported online in the journal PLoS ONE, the researchers isolated and characterized a novel type of cardiac stem cell from the heart tissue of middle-aged mice following a heart attack.

Then, in one experiment, they placed the cells in the culture dish and showed they had the ability to differentiate into cardiomyocytes, or “beating heart cells,” as well as endothelial cells and smooth muscle cells, all of which make up the heart.

In another, they made copies, or “clones,” of the cells and engrafted them in the tissue of other mice of the same genetic background who also had experienced heart attacks. The cells induced angiogenesis, or blood vessel growth, or differentiated, or specialized, into endothelial and smooth muscle cells, improving cardiac function.

“These findings are very exciting,” said first author Jianqin Ye, PhD, MD, senior scientist at UCSF’s Translational Cardiac Stem Cell Program. First, “we showed that we can isolate these cells from the heart of middle-aged animals, even after a heart attack.” Second, he said, “we determined that we can return these cells to the animals to induce repair.”

Importantly, the stem cells were identified and isolated in all four chambers of the heart, potentially making it possible to isolate them from patients’ hearts by doing right ventricular biopsies, said Ye. This procedure is “the safest way of obtaining cells from the heart of live patients, and is relatively easy to perform,” he said.

“The finding extends the current knowledge in the field of native cardiac progenitor cell therapy,” said senior author Yerem Yeghiazarians, MD, director of UCSF’s Translational Cardiac Stem Cell Program and an associate professor at the UCSF Division of Cardiology. “Most of the previous research has focused on a different subset of cardiac progenitor cells. These novel cardiac precursor cells appear to have great therapeutic potential.”

The hope, he said, is that patients who have severe heart failure after a heart attack or have cardiomyopathy would be able to be treated with their own cardiac stem cells to improve the overall health and function of the heart. Because the cells would have come from the patients, themselves, there would be no concern of cell rejection after therapy.

The cells, known as Sca-1+ stem enriched in Islet (Isl-1) expressing cardiac precursors, play a major role in cardiac development. Until now, most of the research has focused on a different subset of cardiac progenitor, or early stage, cells known as, c-kit cells.

The Sca-1+ cells, like the c-kit cells, are located within a larger clump of cells called cardiospheres.

The UCSF researchers used special culture techniques and isolated Sca-1+ cells enriched in the Isl-1expressing cells, which are believed to be instrumental in the heart’s development. Since Isl-1 is expressed in the cell nucleus, it has been difficult to isolate them but the new technique enriches for this cell population.

The findings suggest a potential treatment strategy, said Yeghiazarians. “Heart disease, including heart attack and heart failure, is the number one killer in advanced countries. It would be a huge advance if we could decrease repeat hospitalizations, improve the quality of life and increase survival.” More studies are being planned to address these issues in the future.

An estimated 785,000 Americans will have a new heart attack this year, and 470,000 who will have a recurrent attack. Heart disease remains the number one killer in the United States, accounting for one out of every three deaths, according to the American Heart Association.

Medical costs of cardiovascular disease are projected to triple from $272.5 billion to $818.1 billion between now and 2030, according to a report published in the journal Circulation.

First author Ye, Henry Shih, Richard E. Sievers, Yan Zhang, and Megha Prasad are with the UCSF Division of Cardiology; Yeghiazarians and Andrew Boyle are with the UCSF Division of Cardiology and the UCSF Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research; William Grossman is with the UCSF Division of Cardiology and the UCSF Cardiovascular Research Institute; Harold S. Bernstein is with the UCSF Cardiovascular Research Institute, the UCSF Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, and the UCSF Department of Pediatrics; Hua Su is with UCSF Department of Anesthesia and Perioperative Care; and Yan Zhou with the UCSF Department of Cell and Tissue Biology.

The study was supported by funds from the Wayne and Gladys Valley Foundation, the UCSF Cardiac Stem Cell Fund and the Harold Castle Foundation.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

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Stem Cell Study in Mice Offers Hope for Treating Heart Attack Patients

Stem Cell Stocks: Mending Scarred Hearts

A new study at Johns Hopkins University has shown that stem cells from patients' own cardiac tissue can be used to heal scarred tissue after a heart attack. This is certainly exciting news considering heart failure is still the No. 1 cause of death in men and women.

The study included 25 heart attack victims, 17 of whom got the stem cell treatment. Those patients saw a 50% reduction in cardiac scar tissue after one year, while the eight control patients saw no improvement.

The procedure involves removing a tiny portion of heart tissue through a needle, cultivating the stem cells from that tissue, and reinserting them in a second minimally invasive procedure, according to Bloomberg.

"If we can regenerate the whole heart, then the patient would be completely normal," said Eduardo Marban, director of Cedars-Sinai Heart Institute who was the study's lead author. "We haven't fulfilled that yet, but we've gotten rid of half of the injury, and that's a good start."

Business section: Investing ideas
Interested in investing in the promise that stem cell therapy holds? For a look at the investing landscape, we compiled a list of the 10 largest companies involved in stem cell therapy.

Do you think this industry will see growth from stem cell research? (Click here to access free, interactive tools to analyze these ideas.)

1. BioTime (NYSE: BTX  ) : Focuses on regenerative medicine and blood plasma volume expanders. Market cap at $291.95M. The company develops and markets research products in the field of stem cells and regenerative medicine. It develops therapeutic products derived from stem cells for the treatment of retinal and neural degenerative diseases; cardiovascular and blood diseases; therapeutic applications of stem cells to treat orthopedic diseases, injuries, and cancer; and retinal cell product for use in the treatment of age-related macular degeneration.

2. Cleveland BioLabs (Nasdaq: CBLI  ) : Market cap at $111.50M. Its products include Protectan CBLB502, a radioprotectant molecule with multiple medical and defense applications for reducing injury from acute stresses, such as radiation and chemotherapy by mobilizing various natural cell protecting mechanisms, including inhibition of apoptosis, reduction of oxidative damage, and induction of factors that induce protection and regeneration of stem cells in bone marrow and the intestines, and Protectan CBLB612, a modified lipopeptide mycoplasma that acts as a stimulator and mobilizer of hematopoietic stem cells to peripheral blood, providing hematopoietic recovery during chemotherapy and during donor preparation for bone marrow transplantation.

3. Gentium: Focuses on the development and manufacture of its primary product candidate, defibrotide, an investigational drug based on a mixture of single-stranded and double-stranded DNA extracted from pig intestines. Market cap at $128.29M. The company develops defibrotide for the treatment and prevention of hepatic veno-occlusive disease (VOD), a condition that occurs when veins in the liver are blocked as a result of cancer treatments, such as chemotherapy or radiation, that are administered prior to stem cell transplantation.

4. Geron (Nasdaq: GERN  ) : Develops biopharmaceuticals for the treatment of cancer and chronic degenerative diseases, including spinal cord injury, heart failure, and diabetes. Market cap at $265.57M. The company has licensing agreement with the University Campus Suffolk to develop human embryonic stem cell-derived chondrocytes for the treatment of cartilage damage and joint disease.

5. Harvard Bioscience: Develops, manufactures, and markets apparatus and scientific instruments used in life science research in pharmaceutical and biotechnology companies, universities, and government laboratories in the United States and internationally. Market cap at $118.28M. Develops devices used by clinicians and researchers in the field of regenerative medicine, including bioreactors for growing tissue and organs outside the body, and injectors for stem cell therapy.

6. Lydall (NYSE: LDL  ) : Designs and manufactures specialty engineered products for thermal/acoustical, filtration/separation, and bio/medical applications in the United States. Market cap at $163.44M. In addition, it offers Cell-Freeze, a medical device used for cryogenic storage of peripheral blood stem cells.

8. Osiris Therapeutics (Nasdaq: OSIR  ) : Focuses on the development and marketing of therapeutic products to treat various medical conditions in the inflammatory, autoimmune, orthopedic, and cardiovascular areas. Market cap at $157.26M. A stem cell company, focuses on the development and marketing of therapeutic products to treat various medical conditions in the inflammatory, autoimmune, orthopedic, and cardiovascular areas.

7. Verastem: Market cap at $229.00M. Focuses on discovering and developing proprietary small molecule drugs targeting cancer stem cells (CSCs) in breast and other cancers.

Interactive Chart: Press Play to compare changes in analyst ratings over the last two years for the stocks mentioned above. Analyst ratings sourced from Zacks Investment Research.

Kapitall's Alexander Crawford does not own any of the shares mentioned above.

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Stem Cell Stocks: Mending Scarred Hearts