Next Generation Regenerative Therapy with Pim-1 Enhanced Cardiac Progenitor Cells

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PROJECT SUMMARY Myocardial regenerative therapy is poised to revolutionize the way heart failure is treated, but further improvements and enhanced products are needed to make this therapy truly safe and efficacious. Our company, CardioCreate, Inc., has pioneered the use of genetic engineering to enhance the regenerative potential of human Cardiac Progenitor Cells (CPCs) intended for autologous therapeutic utilization. CPCs support myocardial repair and improve cardiac performance through reduction of scar size and increased cardiac output. Pim-1, an endogenous constitutively activated enzyme found within CPCs, is produced in response to stress or pathologic injury in the myocardium. Pim-1 up-regulation enhances cell survival through mediating transcription, cell growth, proliferation, survival, and expansion of the CPC pool. Our legacy of over a decade of research on Pim-1 biology culminates with demonstration of remarkable regenerative effects mediated by adoptively transferred human Pim-1 enhanced CPCs in rodent and swine models with significantly improved cardiac performance relative to unmodified CPCs, bone marrow stem cells and mesenchymal stem cells. Our studies with human Pim-1 enhanced CPCs have also demonstrated the reversal of aging affects on human CPCs, such as down regulation of senescence markers, increased telomere length and mitochondrial activity and the enhancement of proliferation. The technology of using autologous Pim-1 enhanced Cardiac Progenitor Cells (CardioEnhancers™) represents a novel and efficacious treatment for heart failure, leading to improved health, longevity and wellbeing of our society. CardioEnhancers™ have the potential to provide a potential treatment and cure for cardiovascular disease, most specifically heart failure, which is the leading cause of death in the United States and equally affects men and women of all ethnicities and races. This proposal represents the convergent evolution of a decade of high-level mechanistic biological research coupled with entrepreneurial implementation of regenerative medicine solutions moving from the laboratory toward clinical setting implementation. In this Phase 1 STTR proposal the focus will be to complete initial in vitro safety profiling through a combination of oncogenicity and genotoxicity assessments necessary for FDA mandated IND approval. The Phase I goal is to generate the first battery of test results requested by the FDA to evaluate the safety profile of CardioEnhancers™. The innovation of this STTR rests in the trajectory toward implementation of next-generation stem cell therapy for treatment of heart failure. The significance of this STTR will allow CardioCreate, Inc. to move forward as a small business towards the objectives of finding an effective and safe therapeutic treatment for heart disease that may be used internationally, providing highly- skilled manufacturing jobs to US citizens and advancing the high-tech scientific achievement for our US research community.