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In vitro and in vivo characteristics of connexin 43-modified human skeletal myoblasts as candidates for prospective stem cell therapy for the failing heart.
- Source :
-
International journal of cardiology [Int J Cardiol] 2014 Apr 15; Vol. 173 (1), pp. 55-64. Date of Electronic Publication: 2014 Feb 20. - Publication Year :
- 2014
-
Abstract
- Background: Previously, connexin 43-modified skeletal myoblasts (MbCx) were shown to reduce the pro-arrhythmic effect during the regeneration of heart tissue in an animal model of infarction. To increase the relevance to clinical implementation, in this study, we introduced connexin 43 into human myoblasts using a highly safe non-viral vector and demonstrated that their transplantation had a positive effect on the function of the injured heart.<br />Methods and Results: Myoblasts were efficiently transfected with a pCiNeo-GJA1 plasmid (65.72%). qPCR analysis revealed over 32-fold higher expression of the connexin 43 gene in the MbCx cell population compared to 'native' controls. The susceptibility of the myoblasts to oxidative stress conditions (p<0.001) and the fusion index (p<0.01) were increased in the MbCx cells. Additionally, we observed changes in the MYOG and MYH2 gene expression levels in the GJA1-modified myoblasts. Finally, we observed a significant improvement in the post-infarction echocardiographic parameters after intervention using MbCx cells compared with non-transfected myoblasts (MbWt) and the control (0.9% NaCl), wherein a significant decrease in the left ventricular area change in the short axis (SAX AC%) was observed at the two-month follow-up (p<0.05 and p<0.01, respectively).<br />Conclusions: We demonstrated the positive effect of connexin 43 overexpression on the biology and function of human skeletal myoblasts in the context of their potential clinical applications. Our preclinical studies using a mouse infarction model indicated the positive effect of MbCx implantation on the function of the injured heart.<br /> (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Animals
Cells, Cultured
Heart Failure pathology
Humans
Mice
Mice, Inbred NOD
Mice, SCID
Myocardial Infarction metabolism
Myocardial Infarction pathology
Myocardial Infarction therapy
Prospective Studies
Connexin 43 biosynthesis
Heart Failure metabolism
Heart Failure therapy
Myoblasts, Skeletal metabolism
Myoblasts, Skeletal transplantation
Stem Cell Transplantation methods
Subjects
Details
- Language :
- English
- ISSN :
- 1874-1754
- Volume :
- 173
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 24636551
- Full Text :
- https://doi.org/10.1016/j.ijcard.2014.02.009