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The effects of mesenchymal stem cells on c-kit up-regulation and cell-cycle re-entry of neonatal cardiomyocytes are mediated by activation of insulin-like growth factor 1 receptor.

Authors: Yu, XY  Geng, YJ  Li, XH  Lin, QX  Shan, ZX  Lin, SG  Song, YH  Li, Y 
Citation: Yu XY, etal., Mol Cell Biochem. 2009 Jun 9.
Pubmed: (View Article at PubMed) PMID:19507001
DOI: Full-text: DOI:10.1007/s11010-009-0170-x

C-kit-positive neonatal cardiomyocytes (NCMs) contribute to myocardial regeneration. However, the myocardium itself cannot give rise to a robust regenerative response owing to the limited numbers of c-kit-positive resident stem cells present in the heart. It has been shown that mesenchymal stem cells (MSCs) can enhance cardiac repair via the release of paracrine factors such as insulin-like growth factor (IGF-1). We investigated whether the increased expression of c-kit in NCMs mediates the beneficial effects of MSCs on cardiac repair. MSCs and NCMs were prepared from Lewis rats and co-cultured in a Transwell system, which allowed the diffusion of secreted factors but prevented cell contact between the two cell types. The proliferation of NCMs was determined by BrdU assay. The expression of c-kit was assessed by real-time PCR and flow cytometry. The apoptosis rate of NCMs in response to hypoxia was determined by flow cytometry. We found that the expression of c-kit in NCMs was increased by paracrine factors released by MSCs. The effect of paracrine factors on c-kit expression was attenuated by IGF-1 receptor-neutralizing antibody. Furthermore, we found that increased c-kit expression requires IGF-1 receptor activation via the phosphatidylinositol 3 kinase/Akt-mediated pathway. These findings provide a new paradigm for the biological effects of IGF-1 and have significant implications for understanding the beneficial effects of MSCs on myocardial regeneration.


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RGD Object Information
RGD ID: 2311507
Created: 2009-07-21
Species: All species
Last Modified: 2009-07-21
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.