Abstract 16457: Transplantation of Human Induced Pluripotent Stem Cells Derived Cardiac Cells for Cardiac Repair
Objective: We investigated cardiac functional improvements using three distinct human induced pluripoent stem cells (hiPSCs)-derived cell populations.
Methods: Cardiac myocytes (CMs), endothelial cells (ECs), and smooth muscle cells (SMCs) were differentiated from DriPS16, a human iPSC line reprogrammed from human dermal fibroblasts. Myocardial ischemia was created by ligation of the 1st diagonal and 1st marginal coronary arteries for 60 min followed by reperfusion (I/R). Two-million each of CMs, ECs, and SMCs were injected into the ischemic myocardium. To prevent cell leakage via injection track, a fibrin patch was applied to the surface of I/R myocardium. Gelatin microsphere encapsulating IGF was loaded in the patch. Three animal groups were: saline injection (I/R, n=6), patch transplantation (P, n=6), patch+intramyocardial injection of three cardiac lineage cells (P+cell, n=6). TUNEL study was performed to determine the apoptosis of host myocytes at day-3 after surgery. Functional studies (1 and 4 weeks follow-up) were assessed by magnetic resonance imaging (MRI) and spectroscopy (MRS). The fate of transplanted cells was determined by immunohistology study.
Results: The transplantation of cardiac cells significantly reduced apoptosis of host myocytes. Significantly increased revascularization at scar boarder zone (BZ) in P+cell group was achieved as compared with I/R and P groups (p<0.05, each). A significantly improved perfusion in BZ area was also achieved in P+cell group. Survival human cells formed cardiac muscle fibers and vessels in porcine heart. MRI study demonstrated that significantly improved LV pump function of P+cell group (EF=54.6±5.6%, p<0.05 for each) as compared with I/R (42.9±3.1%) and P (43.4±4.6%) groups. Similarly, the thickening fraction of infarct zone (IZ) and BZ were observed in P+cell (6.7±2.3, p<0.05 for each) group as compared with I/R (-9.7±6.9) and P (-8.1±7) groups. Systolic wall stress of IZ was significantly lower (144± 25 Pa, p<0.05, for each) in P+cell group as compared with I/R (219±38 Pa) and P (216±44 Pa) groups.
Conclusion: These findings demonstrate that transplantation of three cardio-vascular cell populations derived from hiPSCs holds a great therapeutic potential for myocardial repair.
- © 2012 by American Heart Association, Inc.