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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Division of Experimental Surgery, McGill University, Montreal, Canada.
Georges
G
Makhoul
Division of Experimental Surgery, McGill University, Montreal, Canada.
Rishi
R
Jurakhan
Division of Experimental Surgery, McGill University, Montreal, Canada.
Prashant Kumar
PK
Jaiswal
Division of Experimental Surgery, McGill University, Montreal, Canada.
Khalid
K
Ridwan
Division of Experimental Surgery, McGill University, Montreal, Canada.
Li
L
Li
Division of Experimental Surgery, McGill University, Montreal, Canada.
Kaviyanka
K
Selvasandran
Research Institute of the McGill University Health Center, Montreal, Canada.
Minh
M
Duong
Department of Experimental Medicine, McGill University, Montreal, Canada.
Adel
A
Schwertani
Division of Experimental Surgery, McGill University, Montreal, Canada; Department of Cardiac Surgery, McGill University, Montreal, Canada. Electronic address: renzo.cecere@muhc.mcgill.ca.
Renzo
R
Cecere
D000818:Animals; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D009206:Myocardium / Q000166:cytology*; D009389:Neovascularization, Pathologic; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D051381:Rats; D011917:Rats, Inbred Lew; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D017077:Culture Media, Conditioned; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D042461:Vascular Endothelial Growth Factor A; D048051:p38 Mitogen-Activated Protein Kinases
Angiogenesis; Cellular cardiomyoplasty; Placenta derived stem cell; Vascular endothelial growth factor