Science Current Events | Science News | Brightsurf.com
 
Email a Friend Send to a friend
Printer Friendly Print Geron Demonstrates hESC-derived cardiomyocytes improve heart function after myocardial infarction

Geron Demonstrates hESC-derived cardiomyocytes improve heart function after myocardial infarction

August 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. 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.

"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.

"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.

Russo Partners, LLC



Related Myocardial Infarction Current Events and Myocardial Infarction News Articles Myocardial Infarction Current Events and Myocardial Infarction News RSS Myocardial Infarction Current Events and Myocardial Infarction News RSS
Survival after heart attack improves in younger women
In recent years, women, particularly younger women, experienced larger improvements in hospital mortality after myocardial infarction (MI) than men, according to a study published in the Oct. 26, 2009 issue of Archives of Internal Medicine.

Cost Effectiveness of Blood Pressure Device Evaluated
A study conducted by the University of Rochester Medical Center (URMC) demonstrates that, for certain patient populations, an experimental device that lowers blood pressure may be a cost effective treatment. The implantable device, called Rheos, is in advanced stages of testing for individuals with drug resistant hypertension.

Drug-eluting stents better than bare-metal stents for heart attack patients
Late-breaking data from the landmark HORIZONS-AMI clinical trial, presented at the 21st annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium, demonstrated that after two years, in heart attack patients, the use of a drug-eluting stent (paclitaxel) was safer and more effective than a bare-metal stent; and that the administration of the anticoagulant medication bivalirudin enhanced safety and efficacy compared to the use of heparin + GPIIb/IIIa inhibitors.

SPIRIT IV trial shows everolimus stent sets new standard for event-free survival
Late-breaking data from SPIRIT IV, a large-scale multi-center study of nearly 4,000 patients in the U.S., shows that an everolimus-eluting stent demonstrated enhanced safety and efficacy in the treatment of de novo native coronary artery lesions when compared to a paclitaxel-eluting stent, and showed that "low late loss" may be achieved with drug-eluting stents without sacrificing safety.

A consistent decline in heart attack rates following the implementation of smoking bans
Strongly enforced legislation to restrict smoking produces rapid and substantial reductions in community rates of heart attack, according to a meta-analysis published today in Circulation, the journal of the American Heart Association.

Pre-hospital organization: The first links in the chain of survival for heart attack patients
Mortality rate following a heart attack has fallen by more than 50% in Europe over the past 25 years. However, because only minor advances in the medical treatment of AMI are expected over the next decade, it is through organisational changes in the pre-hospital phase that mortality rate will continue this decline to below 5%.

Stent for life initiative
Primary angioplasty (with stent implantation) is the most effective therapy for acute myocardial infarction (AMI), but it is not available to many patients, even though most European countries have sufficient resources (ie, catheterisation laboratories) for its wider use.

GERD negatively impacts sleep quality, results in considerable economic burden
There has been much debate about the relationship between gastroesophageal reflux disease (GERD) and sleep.

Results from the Kyoto heart study
The KYOTO HEART Study, which took place in Japan between January 2004 and January 2009, shows that the addition of valsartan to conventional antihypertensive treatment to improve blood pressure control is associated with an improved cardiovascular outcome in Japanese hypertensive patients at high risk of CVD events.

Aspirin works for primary prevention in moderate and high risk diabetics
The beneficial effects of aspirin in primary prevention of cardiovascular events i.e. stroke, MI and cardiac death are known and generally accepted.
More Myocardial Infarction Current Events and Myocardial Infarction News Articles
Myocardial Infarction: An Incredibly Easy! Miniguide

Myocardial Infarction: An Incredibly Easy! Miniguide
by Springhouse (Editor)

Pocket-sized guide to risk factors, pathophysiology, prevention, physical examination, diagnostic tests, drug therapy, complications, recovery, patient education, and more. Includes key concepts, quizzes, memory joggers, and color illustrations of pathophysiology. Two-tone format. For nurses. Trim size: 5.5 x 4.5 inches. Softcover. DNLM: Myocardial Infarction Handbooks.

New Paradigms in the Treatment of Myocardial Infarction (NCME Video 857)

New Paradigms in the Treatment of Myocardial Infarction (NCME Video 857)
Also With: Network for Continuing Medical Education (Primary Contributor), Deepak L. Bhatt (Primary Contributor), Marc S. Sabatine (Primary Contributor)

How is the standard of care for patients with MI being redefined in 2005? In these live, interactive dinner forums, two national cardiovascular experts present results from recent clinical trials that may impact future guidelines. Topics include the first major milestone in over a decade for incremental pharmacologic reperfusion and mortality reduction in STEMI; fine points in choosing PCI versus thrombolysis in STEMI; the role of troponins, hs-CRP, and other CV risk markers in targeting therapies in UA/NSTEMI; and interpreting the latest results from drug-eluting stent trials. A community cardiovascular expert from your area will join the national faculty to discuss how to incorporate new evidence-based medicine into actionable critical pathways at your own hospital. Late-breaking...

  Adult Acute Myocardial Infarction [VHS]
Starring: Aha



Myocardial Infarction (Heartbreak)

Myocardial Infarction (Heartbreak)
Swamp Dogg (Primary Contributor)



Prevention of Myocardial Infarction

Prevention of Myocardial Infarction
by JoAnn E. Manson (Editor), Paul M. Ridker (Editor), J. Michael Gaziano (Editor), Charles H. Hennekens (Editor)

Harvard Medical School, Boston, MA. Clinical research on coronary disease prevention. Chapters on lifestyle modifications, hypertension and hypercholesterolemia, antiplatelet, antioxidant, and estrogen replacement therapies. For health care providers, general internists, and physicians.

Magnesium Malate 150 mg - 120 VegCapsules

Magnesium Malate 150 mg - 120 VegCapsules
by NutraMedix Inc

Magnesium is an essential mineral that is required by every cell in the human body and is important for helping to maintain normal cardiovascular, muscle, nerve, bone and cellular function.

Mini Heart Set Model

Mini Heart Set Model
by Anatomical

This Mini Heart Set Model contains 3 hearts. First shows normal heart anatomy. Also has Myocardial Infarction heart demonstrating a partially healed, thinned, and discolored 5 infarcted areas. Includes a thrombus in the apex of the heart. Also contains a heart demonstrating Congestive Heart Failure as a result of hypertension. The left ventricle hypertrophy and the correspondingly enlarged and distorted shape of the heart is shown both internally and externally. All models are approximately 50% actual size. Normal and MI hearts: 4"x 2-1/4"x 1-3/4". CHF: 4"x 2-1/2"x 2-1/4".

Critical Care Compendium

Critical Care Compendium
by Mind-Forge Education Services LLC

This is a collection of Self Learning Modules and pocket guides. Below are some of the modules and pocket guides in this product. **A quick handy guide to quickly interpret the 12 lead electrocardiogram, identify ischemia, reciprocal changes and to quickly localize a myocardial infarction and involved coronary arteries. **A brief presentation on atrial fibrillation/flutter, optimal monitoring leads, causes and complications related to open heart surgery. **A brief over view of current Advanced Cardiac Life Support treatment algorithms. **ACLS 2006 Code Drugs: Detailed description of 2006 ACLS code drugs and drip charts. (Current for 2007) **A detailed guide to the autonomic nervous system with emphasis placed on parasympathetic and sympathetic involvement and pharmacological...

New Paradigms in the Treatment of Myocardial Infarction (NCME Video 857)

New Paradigms in the Treatment of Myocardial Infarction (NCME Video 857)
Also With: Network For Continuing Medical Education (Primary Contributor), Deepak L. Bhatt (Primary Contributor), Marc S. Sabatine (Primary Contributor)

How is the standard of care for patients with MI being redefined in 2005? In these live, interactive dinner forums, two national cardiovascular experts present results from recent clinical trials that may impact future guidelines. Topics include the first major milestone in over a decade for incremental pharmacologic reperfusion and mortality reduction in STEMI; fine points in choosing PCI versus thrombolysis in STEMI; the role of troponins, hs-CRP, and other CV risk markers in targeting therapies in UA/NSTEMI; and interpreting the latest results from drug-eluting stent trials. A community cardiovascular expert from your area will join the national faculty to discuss how to incorporate new evidence-based medicine into actionable critical pathways at your own hospital. Late-breaking...

Primary Angioplasty: Mechanical Interventions for Acute Myocardial Infarction, Second Edition

Primary Angioplasty: Mechanical Interventions for Acute Myocardial Infarction, Second Edition
by David Antoniucci (Editor)

Key features:

REVISION OF A BESTSELLER - the Second Edition is a critical guide on the rationale, techniques, and effectiveness of direct percutaneous mechanical revascularization for acute myocardial infarction, to help physicians keep up with the changing times

COMPREHENSIVE - Guides experienced interventional cardiologists, as well as trainees, through the angioplasty process safely and effectively, helping physicians improve patient outcomes

BROAD TREATMENT TECHNIQUES - on stenting, thrombectomy, atherectomy, and others, help physicians combat atherosclerotic plaque and give patients the best care possible

DETAILED MANAGEMENT STRATEGIES - for traditional cases, as well as for the special needs of diabetic, elderly, and female patients, equip clinicians with...

© 2009 BrightSurf.com