Navigation Links
Geron Demonstrates hESC-derived cardiomyocytes improve heart function after myocardial infarction
Date:8/27/2007

MENLO PARK, Calif., Aug. 27, 2007 Geron Corporation (Nasdaq: GERN) today reported its scientists and collaborators have demonstrated that human embryonic stem cell (hESC)-derived cardiomyocytes improve heart function when transplanted after myocardial infarction.

Published online Aug. 26 in Nature Biotechnology, the landmark study is the first to document the potential clinical utility of regenerating damaged heart muscle by injecting hESC-derived cardiomyocytes directly into the site of the infarct. In addition, the research confirms the effectiveness of a scalable production system that enables Geron to manufacture the cardiomyocytes for use in ongoing large animal studies and, ultimately, testing in humans.

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. Gerons 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.

This is one of the most important publications on hESCs for Geron to date, said Thomas B. Okarma, Ph.D., M.D., Gerons 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.

Were 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.


'/>"/>
Contact: Sion Rogers
sion.rogers@russopartnersllc.com
212-845-4292
Russo Partners, LLC
Source:Eurekalert

Related biology news :

1. Study Demonstrates Gene Expression Microarrays are Comparable and Reproducible
2. MRSA study demonstrates need for frequent hand washing and environmental disinfection in health care settings
3. Sangamo BioSciences demonstrates its ZFP treatment protects cells from HIV infection
4. New research demonstrates bone-marrow derived stem cells can reverse genetic kidney disease
5. Xie Lab demonstrates the role of microRNA pathway
6. Adding Radiation Therapy To Chemotherapy Improves Survival In Patients With High-risk Breast Cancer
7. Emory Study Tests Bone Marrow Stem Cells to Improve Circulation in Legs
8. Improved Outcomes Releases GeneLinker(TM) Gold and Platinum Version 4.6
9. Discovery of key proteins shape could lead to improved bacterial pneumonia vaccine
10. Novel ultrafast laser detection of cancer cells also may improve understanding of stem cells
11. Vascular structure and function improve with diet and exercise
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/25/2016)...  Glencoe Software, the world-leading supplier of image data ... provide the data management solution OMERO Plus for the ... Photo - http://photos.prnewswire.com/prnh/20160125/325328LOGO ... Phenotypic analysis measures the characteristics and behavior of ... states such as health and disease, the presence or ...
(Date:1/22/2016)... , Jan. 22, 2016 ... addition of the "Global Biometrics Market ... their offering. --> http://www.researchandmarkets.com/research/p74whf/global_biometrics ... "Global Biometrics Market in Retail Sector ... --> Research and Markets ( ...
(Date:1/20/2016)... A market that just keeps on growing. Molecular Diagnostics ... genomics knowledge. Learn all about it in this new ... trends are pushing market growth and company valuations. Trends ... pathogen evolution - next generation sequencing - emergence of ... the role of genetic material in Disease and Health ...
Breaking Biology News(10 mins):
(Date:2/8/2016)... ... February 08, 2016 , ... Franz Inc. , ... Database technology, today announced the availability of AllegroGraph 6, the leading Semantic Graph ... Cloudera Certified Technology Program (CCPT). AllegroGraph is the first Semantic Graph Database ...
(Date:2/8/2016)... -- Diplomat Pharmacy, Inc. (NYSE: DPLO) announced today that its new website has gone live. On Thursday, ... mobile-friendly. Visit the new site: www.diplomat.is ... ... ... "The goal was to reimagine the website and create ...
(Date:2/6/2016)... Virginia (PRWEB) , ... February 06, 2016 , ... ... E-mail: amitchell(at)cee(dot)org , The Center for Excellence in Education Sponsors Teacher Training ... VA – February 4, 2016 – The Center for Excellence in Education (CEE) ...
(Date:2/5/2016)... 5, 2016 On Thursday, February 11, ... for community, health and disaster services, and the ... to enhance care coordination and service delivery for the ... need and to better connect service providers to the ... San Diego has handled more than ...
Breaking Biology Technology: