| 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: 2012-10-16 |
Medline Journal Info:
|
Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
|
Languages: eng Pagination: 60-70 Citation Subset: IM |
Affiliation:
|
Department of Pathology, University of Cincinnati, Cincinnati, OH 45267-0529, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 HL080686-05/HL/NHLBI NIH HHS; R01 HL087246-05/HL/NHLBI NIH HHS; R01 HL087288-05/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 HL107957-02/HL/NHLBI NIH HHS; R37 HL074272-09/HL/NHLBI NIH HHS; R37-HL074272/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/MicroRNAs |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Effects of repeated treatment with phosphodiesterase-4 inhibitors on cAMP signaling, hippocampal cel...
Next Document: Neonatal mouse-derived engineered cardiac tissue: a novel model system for studying genetic heart di...