Document Detail


Reprogramming of skeletal myoblasts for induction of pluripotency for tumor-free cardiomyogenesis in the infarcted heart.
MedLine Citation:
PMID:  21566212     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: Skeletal myoblasts (SMs) with inherent myogenic properties are better candidates for reprogramming to pluripotency.
OBJECTIVE: To reprogram SMs to pluripotency and show that reprogrammed SMs (SiPS) express embryonic gene and microRNA profiles and that transplantation of predifferentiated cardiac progenitors reduce tumor formation.
METHODS AND RESULTS: The pMXs vector containing mouse cDNAs for Yamanaka's quartet of stemness factors were used for transduction of SMs purified from male Oct4-GFP(+) transgenic mouse. Three weeks later, GFP(+) colonies of SiPS were isolated and propagated in vitro. SiPS were positive for alkaline phosphatase, expressed SSEA1, and displayed a panel of embryonic stem (ES) cell-specific pluripotency markers. Embryoid body formation yielded beating cardiomyocyte-like cells, which expressed early and late cardiac-specific markers. SiPS also had an microRNA profile that was altered during their cardiomyogenic differentiation. Noticeable abrogation of let-7 family and significant up-regulation of miR-200a-c was observed in SiPS and SiPS-derived cardiomyocytes, respectively. In vivo studies in an experimental model of acute myocardial infarction showed extensive survival of SiPS and SiPS-derived cardiomyocytes in mouse heart after transplantation. Our results from 4-week studies in DMEM without cells (group 1), SMs (group-2), SiPS (group-3), and SiPS-derived cardiomyocytes (group 4) showed extensive myogenic integration of the transplanted cells in group 4 with attenuated infarct size and improved cardiac function without tumorgenesis.
CONCLUSIONS: Successful reprogramming was achieved in SMs with ES cell-like microRNA profile. Given the tumorgenic nature of SiPS, their predifferentiation into cardiomyocytes would be important for tumor-free cardiogenesis in the heart.
Authors:
Rafeeq P H Ahmed; Husnain K Haider; Stephanie Buccini; Longhu Li; Shujia Jiang; Muhammad Ashraf
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-05-12
Journal Detail:
Title:  Circulation research     Volume:  109     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-24     Completed Date:  2011-08-22     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  60-70     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation
Female
Heart Neoplasms / prevention & control*
Induced Pluripotent Stem Cells / transplantation*
Male
Mice
Mice, Inbred C57BL
MicroRNAs / analysis
Muscle Development
Myoblasts, Skeletal / cytology*
Myocardial Infarction / therapy*
Myocytes, Cardiac / cytology,  physiology,  transplantation*
Regeneration
Systole
Ventricular Function, Left
Grant Support
ID/Acronym/Agency:
HL080686/HL/NHLBI NIH HHS; HL087246/HL/NHLBI NIH HHS; HL087288/HL/NHLBI NIH HHS; HL089535/HL/NHLBI NIH HHS; HL106190/HL/NHLBI NIH HHS; HL107957/HL/NHLBI NIH HHS; R01 HL080686/HL/NHLBI NIH HHS; R01 HL080686-05/HL/NHLBI NIH HHS; R01 HL087246/HL/NHLBI NIH HHS; R01 HL087246-05/HL/NHLBI NIH HHS; R01 HL087288/HL/NHLBI NIH HHS; R01 HL087288-05/HL/NHLBI NIH HHS; R01 HL089535/HL/NHLBI NIH HHS; R01 HL089535-05/HL/NHLBI NIH HHS; R01 HL106190/HL/NHLBI NIH HHS; R01 HL106190-02/HL/NHLBI NIH HHS; R01 HL107957/HL/NHLBI NIH HHS; R01 HL107957-02/HL/NHLBI NIH HHS; R37 HL074272/HL/NHLBI NIH HHS; R37 HL074272-09/HL/NHLBI NIH HHS; R37-HL074272/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/MicroRNAs
Comments/Corrections

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