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Conditioned medium of H9c2 triggers VEGF dependent angiogenesis by activation of p38/pSTAT3 pathways in placenta derived stem cells for cardiac repair

Makhoul, Georges, Jurakhan, Rishi, Jaiswal, Prashant Kumar, Ridwan, Khalid, Li, Li, Selvasandran, Kaviyanka, Duong, Minh, Schwertani, Adel, Cecere, Renzo
Life sciences 2016 v.153 pp. 213-221
angiogenesis, bone marrow, cardiomyocytes, cell culture, cell differentiation, cell free system, cell membranes, connexins, culture media, cytoplasm, echocardiography, humans, myosin heavy chains, placenta, rats, stem cells, troponin I, vascular endothelial growth factors
Cardiomyocytes are understood to possess a limited regenerative capacity. Any myocardial insult leads to an irreversible injury. Mesenchymal stem cell differentiation into cardiomyocyte-like cells stands as one of the leading experimental therapies. However, a candidate cell source has yet to be defined. Here, we examined the in vitro and in vivo cardiac differentiation potential of human placenta derived stem cells (hPDSCs); a unique, abundant, and non-immunogenic cell source.H9c2 cell culture medium was applied to hPDSCs at different ratios for a period of 4weeks. In parallel, hPDSCs, human bone marrow stem cells, or cell free culture medium was injected in peri-infarcted regions induced in rat hearts.In vitro, hPDSCs pre-conditioned with H9c2 cell culture medium proportionally over-expressed alpha sarcoplasmic actinin and displaced connexin 43 from the cytoplasm to the cell membrane. Additionally, pre-conditioning promoted hPDSCs survival and triggered vascular endothelial growth factor (VEGF) dependent angiogenesis by activating the pAkt and p38MAPK/pSTAT3 pathways. In vivo, echocardiography analysis showed a significant improvement in cardiac parameters in the rats injected with hPDSCs, similar to the human bone marrow stem cells injected group. Moreover, hPDSCs detected within rat cardiac tissues expressed troponin I and myosin heavy chain. In accordance with the pre-conditioning findings, VEGF positive neovessels were observed in hearts injected with hPDSCs.hPDSCs have the potential to differentiate into cardiac-like cells and induce angiogenesis via paracrine effects. With the advantages of easy availability and young age, these cells could be more suitable for clinical translation.