Document Detail


Stem cell-based delivery of Hypoxamir-210 to the infarcted heart: implications on stem cell survival and preservation of infarcted heart function.
MedLine Citation:
PMID:  22648522     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study seeks to test our hypothesis that transgenic induction of miR-210 in mesenchymal stem cells (MSC) simulates the pro-survival effects of ischemic preconditioning (IPC) and that engraftment of (PC)MSC helps in the functional recovery of ischemic heart by miR-210 transfer to host cardiomyocytes through gap junctions. miR-210 expression in MSC was achieved by IPC or nanoparticle-based transfection of miR-210 plasmid ((miR)MSC) and functional recovery of the infarcted heart of rat transplanted with (PC)MSC or (miR)MSC was evaluated. Both (PC)MSC and (miR)MSC showed higher survival under lethal anoxia as compared to (non-PC)MSC and scramble-transfected MSC ((Sc)MSC) controls with concomitantly lower CASP8AP2 expression. Similarly, both (PC)MSC and (miR)MSC survived better and accelerated functional recovery of ischemic heart post-transplantation. To validate our hypothesis that MSC deliver miR-210 to host cardiomyocytes, in vitro co-culture between cardiomyocytes and (PC)MSC or (miR)MSC (using (non-PC)MSC or (Sc)MSC as controls) showed co-localization of miR-210 with gap-junctional connexin-43. miR-210 transfer to cardiomyocytes was blocked by heptanol pretreatment. Moreover, higher survival of cardiomyocytes co-cultured with (PC)MSC was observed with concomitant expression of CASP8AP2 as compared to cardiomyocytes co-cultured with (non-PC)MSC thus suggesting that miR-210 was translocated from MSC to protect host cardiomyocytes. Induction of miR-210 in MSC promoted their survival post-engraftment in the infarcted heart. Moreover, direct transfer of pro-survival miR-210 from (miR)MSC to host cardiomyocytes led to functional recovery of the ischemic heart.
Authors:
Ha Won Kim; Shujia Jiang; Muhammad Ashraf; Khawaja Husnain Haider
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-05-31
Journal Detail:
Title:  Journal of molecular medicine (Berlin, Germany)     Volume:  90     ISSN:  1432-1440     ISO Abbreviation:  J. Mol. Med.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-20     Completed Date:  2013-01-02     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  9504370     Medline TA:  J Mol Med (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  997-1010     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of Cincinnati, 231-Albert Sabin Way, Cincinnati, OH 45267, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Survival
Cells, Cultured
Coculture Techniques
Female
Gap Junctions / metabolism
Gene Transfer Techniques*
Heart / physiopathology
Male
Mesenchymal Stem Cell Transplantation / methods*
Mesenchymal Stromal Cells / cytology*,  metabolism
MicroRNAs / administration & dosage*,  genetics,  metabolism,  therapeutic use*
Myocardial Infarction / genetics,  physiopathology,  surgery,  therapy*
Myocytes, Cardiac / cytology,  metabolism
Rats
Rats, Inbred F344
Up-Regulation
Grant Support
ID/Acronym/Agency:
HL-087246/HL/NHLBI NIH HHS; HL-087288/HL/NHLBI NIH HHS; HL-089535/HL/NHLBI NIH HHS; HL106190-01/HL/NHLBI NIH HHS; R01 HL087288/HL/NHLBI NIH HHS; R01 HL089535/HL/NHLBI NIH HHS; R01 HL106190/HL/NHLBI NIH HHS; R37 HL074272/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/MIRN210 microRNA, rat; 0/MicroRNAs
Comments/Corrections

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