About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Heart Function After Myocardial Infarction Shows Progress Due to HESC-derived Cardiomyocytes

by Medindia Content Team on August 29, 2007 at 5:41 PM
Font : A-A+

Heart Function After Myocardial Infarction Shows Progress Due to HESC-derived Cardiomyocytes

A new research by the Geron cooperation scientists and collaborators show that heat repair by human embryonic stem cell( hESC)-derived cardiomyocytes show good progress. The function of the heart after myocardial infarction also shows great improvement. This landmark study by the Geron is the first to document the probable clinical usefulness of reviving damaged heart muscle by injecting hESC-derived cardiomyocytes directly into the spot of the infarct. The research would enable the cooperation to manufacture the cardiomyocytes in a scaleable production system for the ongoing research in large animals and finally to test in humans. The research is published online in Nature Biotechnology.

The study describes the feeder- and serum-free, scalable production of hESC-derived cardiomyocytes, their survival in the infarct zone of rats when transplanted four days after infarction, and echocardiographic and MRI evidence of significant improvement in cardiac structure and contractile function. Geron's scientists conducted the study in collaboration with Charles Murry, M.D., Ph.D., and Michael Laflamme, M.D., Ph.D., at the University of Washington.

Advertisement

"This is one of the most important publications on hESCs for Geron to date," said Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer. "Our cardiomyocytes are the first human cardiac cells shown to survive after injection into an infarcted ventricle and to produce significant improvement in heart function. hESCs are the only cell type shown definitively to form cardiomyocytes."

Approximately 5.2 million people in the United States suffer from heart failure, and approximately 865,000 people experience myocardial infarction each year. About 36% of this population progresses to heart failure within five years of a first infarction. More than one-third of all heart failure patients die within two years of diagnosis.
Advertisement

"We're developing our cardiomyocyte product, GRNCM1, to address the large unmet need in heart failure," Dr. Okarma added. "We expect GRNCM1 to be our second hESC-derived cell type to enter clinical development."

Production and Characterization of hESC-derived Cardiomyocytes In the study, researchers produced human cardiomyocytes from hESCs using a sequential, directed differentiation protocol that did not rely on serum or feeder cells. The procedure was scalable and efficient, with each hESC producing approximately three human cardiomyocytes. After final enrichment, greater than 80% of the cells were cardiomyocytes. The hESC-derived cardiomyocytes displayed surface and intracellular markers, as well as electrophysiologic and pharmacologic properties consistent with human cardiomyocytes, the majority of which represented ventricular cardiomyocytes. Engraftment Following Transplantation.

To enable survival in the heart, the hESC-derived cardiomyocytes were suspended in a cocktail of survival factors that had been experimentally determined to dramatically enhance cell survival after injection into the infarcted ventricular wall. Four weeks later, tissue sections from the infarcted hearts were examined for the presence of the human cells. The vast majority of human cardiomyocytes were localized in the central region of the infarct, suggesting that the cells were capable of engraftment in the hostile environment of the infarct zone. Moreover, a portion of the cardiomyocytes was mitotic after injection, possibly enhancing their regenerative efficiency. The grafts also induced a brisk, host-derived angiogenic response: all the implants contained numerous capillaries lined with rat endothelial cells.

Safety No teratomas, tumor masses, or aberrant structures were seen in any of the hearts receiving hESC-derived cardiomyocytes. A highly sensitive PCR assay was used to determine whether any hESC-derived cells had migrated to other non-cardiac organs. None were detected in brain, kidney, liver, lung or spleen, indicating the absence of migration of the injected cells from the heart.

Impact of Transplanted hESC-derived Cardiomyocytes on Cardiac Structure and Function

To assess the impact of injected cells on cardiac structure and function, all animals received echocardiography at baseline (two days after infarction but two days prior to cell injection) and at four weeks post cardiomyocyte implantation. All animals exhibited significant cardiac dysfunction two days post infarct. On average, left-ventricular end diastolic and systolic diameters increased by 10% and 42%, respectively, and fractional shortening decreased by 40% compared to uninfarcted controls.

Four days after infarction, animals were injected with 10 million hESC-derived cardiomyocytes suspended in the survival cocktail. Animals injected with either the survival cocktail alone, serum-free media without cells, or equivalent numbers of non-cardiac hESC-derived cells suspended in the survival cocktail served as control groups.

Echocardiography performed four weeks after cell implantation showed attenuation of left-ventricular end-diastolic and end-systolic diameters in animals receiving cardiomyocytes versus all three control groups. In addition, fractional shortening was significantly improved (0.01) in animals that received cardiomyocytes compared to all three control groups. MRI analysis showed improved left-ventricular ejection fraction (p=0.05) in the cardiomyocyte-treated rats compared to controls, as well as a 2.5-fold increase in systolic wall thickening in the infarct zone relative to controls (0.01).

Significance This study is the first to document the potential clinical utility of regenerating damaged heart muscle by injecting hESC-derived cardiomyocytes directly into the infarct zone of the heart. The survival cocktail administered with the cells enables their long-term survival in the infarcted muscle. The injected cells stimulate endogenous blood vessel formation, possibly contributing to both cell survival and improved contractile function. The scalable production system allows for production runs at sufficient scale for large animal studies (ongoing) as well as for ultimate testing in humans.

Source: Eurekalert
BIN/C
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
News Category
What's New on Medindia
Health Benefits of Sea Buckthorn
Contraceptive Pills in Polycystic Ovary Syndrome (PCOS) Curtail Type 2 Diabetes Risk
Mushroom May Help Cut Down the Odds of Developing Depression
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Heart Healthy Heart Statins Mitral Valve Prolapse Aortic Valve Stenosis Cardiac Markers Pericarditis Cardiogenic Shock 

Recommended Reading
A New Milestone in Stem Cell Research
patients who have recently suffered a major heart attack will be injected with selected stem cells ....
Aortic Valve Stenosis
Aortic valve Stenosis is an abnormal narrowing of the c valve. Symptoms include angina, and that of ...
Cardiac Markers
Cardiac markers are biomarkers which are measured to evaluate the function of heart. The test for tr...
Cardiogenic Shock
Cardiogenic shock is defined as reduced cardiac output due to inability of the heart to pump adequat...
Mitral Valve Prolapse
Mitral Valve Prolapse is a relatively common condition and causes leakage of blood through the valve...
Pericarditis
Pericarditis occurs when the pericardium gets inflamed. Pericarditis is characterized by severe ches...
Statins
Statins are new wonder drugs that are proving to be efficacious, not merely in relieving symptoms bu...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use