Abstract 12291: Structural, Functional And Bioenergetic Benefits Of Human Vascular Cell Transplantation Into Acutely Infarcted Swine Hearts
Objective We sought to examine the beneficial effects and underlying mechanisms of transplantation of hiPSC-derived vascular cells (VC, endothelial and smooth muscle cells) into infarcted swine hearts.
Methods & Results Immuno-suppressed female Yorkshire pigs were assigned to groups of: i) LAD ligation for 60 min followed by reperfusion (I/R) (MI, n=15), ii) I/R + 4×106 VCs using a novel fibrin patch enhanced delivery system (CELL, n=16), and iii) size-matched normal pigs (NL, n=11). 6 swine per each group were given BrdU (10 mg/kg/day) for 7 days. At 4 weeks (WK) post infarction, the CELL group showed significantly better LV function than the MI group (MRI, p<0.05), which was accompanied by attenuation of myocardial hypertrophy, and reduction of wall stress and scar size. VC proliferated and persistently engrafted for at least 4 WK post transplantation based on GFP staining, with a portion of which integrated into host vessels. VC induced neo-vascularization and significantly improved border zone (BZ) myocardial blood flow (p<0.05, microspheres). VC also recruited c-kit+ cells to the injury site, many of which co-expressed GATA4. The CELL group showed a significantly higher BrdU incorporation rate in the BZ cardiomyocytes than the MI group (BrdU+Myocyte%: 8.7±2.0% in CELL vs. 1.9±0.4% in MI, p<0.05) suggesting increased BZ cardiomyocyte turnover. Using a novel magnetic resonance spectroscopy technique we observed severe abnormalities of ATP turnover rate in the BZ of untreated MI hearts (61% reduction vs. NL hearts, p<0.05).These abnormalities were abolished in the VC treated hearts.
Conclusion VC transplantation markedly attenuated the progression of post-infarction LV remodeling. The beneficial effects did not directly contribute from the regeneration of engrafted cells, rather resulted from VC-associated paracrine effects, which include protection of cardiomyocytes, stimulation of neo-vascularization, recruitment of endogenous progenitor cells and enhancement of cardiomyocyte regeneration from endogenous progenitor cells. Whether preservation of bioenergetic capability in treated hearts was directly related to VC signaling and/or a secondary consequence of better preserved LV perfusion and structure remains to be defined.
- © 2012 by American Heart Association, Inc.