Surface Biomarker Code for Isolation of Cardiac Progenitors and Distinct Cardiac Lineages

Funding Type: 
Tools and Technologies II
Grant Number: 
RT2-01912
Investigator: 
ICOC Funds Committed: 
$0
Public Abstract: 
Nearly 5 million people in the US are afflicted with heart failure with an additional 550,000 new cases diagnosed each year. Despite current treatment regimens, heart failure still remains the leading cause of morbidity and mortality in the US and developed world due to failure to adequately replace lost ventricular myocardium from ischemia-induced infarct. Consequently, stem cell-based therapies to replace lost or damaged ventricular myocardium hold great promise. However, pluripotent stem cells carry a risk of uncontrolled growth and subsequent tumors/teratomas. Furthermore, cell transplantation of heterogeneous populations of cardiac and non-cardiac tissue may result in an arrhythmic substrate in patients' hearts potentially leading to sudden cardiac death. Thus, creating protocols that allow for purification of homogeneous populations of differentiating cardiac subpopulations, in particular ventricular myocytes, is critical toward realizing the potential of stem cell therapy in heart failure patients. Toward this end, we have proposed to develop tools and technologies that address this rate-limiting issue by identifying surface biomarker codes that specifically define subpopulations of differentiating hPSC-derived cardiomyocytes. Moreover, we will use this code to develop protocols to FACS purify progenitor as well as mature hPSC-derived cardiomyocytes. These protocols will be applicable to cardiomyocytes derived from not only PSCs but also other cell populations including transdifferentiation of non-cardiac tissues and cardiac progenitor cells. As a result, this precise selection of specific populations of hPSC-derived cardiomyocytes will provide a source of human cardiomyocytes 1) to further study the development and expansion of differentiating hPSC-derived cardiac lineages; 2) to model cardiac diseases which affect specific cardiac cell types, including long QT syndrome, atrial/ventricular fibrillation, cardiac conduction blocks and cardiomyopathies; 3) to screen drugs for future cardiac treatments, and 4) to implement regenerative cell therapies for myocardial infarctions.
Statement of Benefit to California: 
Nearly 5 million people in the US are afflicted with heart failure with an additional 550,000 new cases diagnosed each year. Despite current treatment regimens, heart failure still remains the leading cause of morbidity and mortality in California, US and developed world because of the inability to adequately replace lost ventricular heart cells from myocardial infarctions or "heart attacks." Though stem cell-based therapies to replace lost or damaged ventricular myocardium hold great promise, pluripotent stem cells carry a risk of uncontrolled growth and subsequent tumors/teratomas. Furthermore, cell transplantation of heterogeneous populations of cardiac and non-cardiac tissue may result in an arrhythmic substrate in patients' hearts potentially leading to sudden cardiac death. Thus, creating protocols that allow for isolation of pure populations of differentiating cardiac subpopulations, in particular ventricular myocytes, is critical toward realizing the potential of stem cell therapy in heart failure patients. Toward this end, we have proposed to create novel tools and strategies for the purification of specific cardiac populations for stem cell-based cardiac regenerative therapies.

© 2013 California Institute for Regenerative Medicine