M T Alrefai, C L Tarola, R Raagas, K Ridwan, M Shalal, N Lomis, A Paul, M D Alrefai, S Prakash, A Schwertani, D Shum-Tim
Objectives: Cell-based therapies have demonstrated variable degrees of success in the management of myocardial infarction and heart failure. By inducing a myocardial infarction in a rat model, the effects of secretome from human induced pluripotent stem cells (HiPSCs) and human mesenchymal stem cells (hMSCs) on cardiac function and remodeling were investigated.
Methods: HiPSCs and hMSCs were cultured and after 12 cycles, secretome was collected. The quantification of stem cell growth factors was measured using the ELISA test. Thirty female Lewis rats underwent surgical ligation of the left coronary artery. The rats were then randomized (n=10/group) to receive one of three treatments injected into the peri-infarct area; normal saline, HiPSC and hMSC. Left ventricular ejection fraction (LVEF), fractional shortening (FS), histology and serum proteomics were evaluated in a blinded fashion both pre-operatively and at 2, 4 and 6 weeks.
Results: ELISA studies revealed, Platelet-derived growth factor (PDGF) concentration of 3.35± 0.031 ng/ml (0.68± 0.027ng/ml) for MSC-CM group, 3.44± 0.042 ng/ml (0.78± 0.03 ng/ml) for the HiPSC-CM group, 3.2± 0.107 ng/ml (0.64±0.013 ng/ml) for the MSC-pre-group, 3.1± 0.075 ng/ml (0.71± 0.013 ng/ml) for the HiPSC-pre group and 3.3± 0.047 ng/ml (0.71± 0.014ng/ml) for the HiPSC-pre-r group at 60 min in comparison to at (0 min).Compared to non-treated (NT), HiPSC and hMSC, treated rats demonstrated significant improvement in LVEF and FS, and significant reduction in scar size (p<0.05) at 4 and 6 weeks. Proteomic analysis detected the presence of Vascular endothelial growth factor (VEGF) in the serum of rats receiving HiPSC, which was absent in the NT and hMSC groups.
Conclusion: The current study demonstrated a significant improvement of cardiac function and remodeling in response to secretome from HiPSCs and hMSCs. These findings suggest that secretome from HiPSCs may have potential therapy for acute myocardial infarction (MI) without the need of stem cell harvesting and implantation.
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