Receiving this Diversity supplement will support my student, Stefan Veizades, who is of Salvadorian (Latino) descent, in his pursuit of a career in academic medicine. Stefan has spent the last summer building his skills in molecular and cellular biology in preparation for further training during his undergraduate years. During the academic year, he will hone and apply these skills to better characterize mesenchymal stem cells isolated from fat that potentially generate functional vessels to serve as natural bypasses for the ischemic myocardium. This project is a natural extension of Aim 2 of my proposal, which identifies novel growth factors and stromal cell subpopulations that may modify the tissue microenvironment and improve the survival of cardiomyocytes derived from human induced pluripotent stem cells in an ischemic model of myocardial infarction. It is unclear whether the stromal sub-populations that we identified in Aim 2 can be stand-alone therapy. End-stage heart failure from ischemic heart disease remains a devastating disease with high morbidity and mortality. It is estimated that one in nine death results from heart failure. Some patients with ischemic heart disease can develop collateral circulation, namely, new vessels in the area of injury that provide natural bypasses for areas of poor blood flow. It remains unclear how these collaterals develop and to what extent they can protect the myocardium from permanent damage. In this proposal, we will use advanced cellular and molecular imaging techniques (e.g., flow cytometry, lineage tracing, single cell sequencing, and small animal imaging studies) to characterize subpopulations of mesenchymal cells isolated from fat that can produce functional vessels in the ischemic microenvironment. If successful, these cells can serve not only serve as adjuvant therapy for supporting the transplantation of iPSC, but also become stand-alone therapy to provide collateral circulation to protect hearts from damage.

Public Health Relevance

One of the ways to treat blocked arteries in the heart is to perform coronary artery bypass grafting, a procedure whereby the surgeon takes a vein or artery from another part of one?s body and creates a new route for blood to flow around the blocked area. In this proposal, we would like to see if special populations of fat cells can form blood vessels to serve as natural bypasses to supply oxygen and nutrients to the heart and preserve its function after a heart attack.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Lee, Albert
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Stanford University
Internal Medicine/Medicine
Schools of Medicine
United States
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Lee, Andrew S; Inayathullah, Mohammed; Lijkwan, Maarten A et al. (2018) Prolonged survival of transplanted stem cells after ischaemic injury via the slow release of pro-survival peptides from a collagen matrix. Nat Biomed Eng 2:104-113
Chung, Kieran S; Nguyen, Patricia K (2018) Non-invasive measures of coronary microcirculation: Taking the long road to the clinic. J Nucl Cardiol 25:2112-2115
Wardak, Mirwais; Nguyen, Patricia K (2018) The Gift of Light: Using Multiplexed Optical Imaging to Probe Cardiac Metabolism in Health and Disease. Circ Cardiovasc Imaging 11:e007597
Lee, Andrew S; Tang, Chad; Hong, Wan Xing et al. (2017) Brief Report: External Beam Radiation Therapy for the Treatment of Human Pluripotent Stem Cell-Derived Teratomas. Stem Cells 35:1994-2000