ASSOCIATE PROFESSOR Microbiology
Mount Sinai School of Medicine
Isolation and Characterization of Human Induced Pleuripotent Stem Cell Cardiomyocytes from Patients with Idiopathic Cardiomyopathy
Background/Hypothesis: Cardiomyopathy is a leading cause of morbidity and mortality worldwide. In roughly 50% of patients no underlying cause is identified (Idiopathic Cardiomyopathy). Our group has recently demonstrated that human Embryonic Stem Cells hESCs can be used to produce homogenous populations of cardiovascular cells, greatly advancing their potential for study of heart disease. Recently, direct reprogramming of human adult somatic cells into hESC-like lines called human induced pluripotent stem (hIPS) cells has been accomplished using defined combinations of factors. We hypothesize that human tissue collected at the time of cardiac surgery can be used to create patient-specific hIPS cell lines from patients with idiopathic and non-idiopathic cardiomyopathy. These lines could then be used to create cardiomyocytes for the development of novel diagnostic tools and treatments for cardiomyopathy. Methods: We will harvest tissue from patients with cardiomyopathy at the time of cardiac surgery. Fibroblasts lines will be used to generate hIPS cells. We will then used our previously described techniques to generate enriched populations of cardioprogenitor cells (CPCs) from the hIPS cells. These IPS derived CPCs will then be subjected to gene, protein and physiologic analysis. Future work will focus on using chemical libraries to identify novel pharmacologic agents. Clinical Significance: The development of technology for the generation of hIPS lines from patients with idiopathic cardiomyopathy has the potential to have a great impact on the diagnosis and treatment of this deadly and prevalent disease. Human iPS cell-derived dysfunctional myocytes can serve as proof of an inheritable form of disease as well as aid in the development of personalized pharmacologic regimens consisting of medications that the patients will best respond. These dysfunctional hiPS cell-derived cardiomyocytes could also be used for a screening of (novel) small molecules to identify new pharmacologic agents.