alexa Induced Pluripotent Stem Cells derived Muscle Progenitors Effectively Mitigate Muscular Dystrophy through Restoring the Dystrophin Distribution | OMICS International | Abstract
ISSN: 2157-7633

Journal of Stem Cell Research & Therapy
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Research Article

Induced Pluripotent Stem Cells derived Muscle Progenitors Effectively Mitigate Muscular Dystrophy through Restoring the Dystrophin Distribution

Wen-Feng Cai1, Wei Huang1, Lei Wang1, Jia-Peng Wang1, Lu Zhang1,2, Muhammad Ashraf3, Shizheng Wu4* and Yigang Wang1*

1Department of Pathology and Lab Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH 45267-0529, USA

2Key Laboratory of Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China

3Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612, USA

4Qinghai Provincial People’s Hospital, 2 Gonghe Rd, Xining, Qinghai, 810007, China

*Corresponding Authors:
Yigang Wang
Department of Pathology and Laboratory Medicine, University of Cincinnati, College of Medicine
231 Albert Sabin Way, Cincinnati, OH, 45267-0529, USA
Tel: +1 513 558 5798
Fax: +1 513 558 5711
E-mail: [email protected]
 
Shizheng Wu
Qinghai Provincial People’s Hospital
2 Gonghe Rd, Xining, Qinghai, 810007, China
Tel: +86 0971 8066386
Fax: +86 0971 8066386
E-mail: [email protected]

Received date: August 31, 2016; Accepted date: September 21, 2016; Published date: September 26, 2016

Citation: Cai WF, Huang W, Wang L, Wang JP, Zhang L, et al. (2016) Induced Pluripotent Stem Cells derived Muscle Progenitors Effectively Mitigate Muscular Dystrophy through Restoring the Dystrophin Distribution. J Stem Cell Res Ther 6:361. doi:10.4172/2157-7633.1000361

Copyright: © 2016 Cai WF, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Duchenne Muscular Dystrophy (DMD) is a recessive form of muscular disorder, resulting from the dystrophin gene mutations in X-chromosome. Application of embryonic stem cells or adult stem cells has demonstrated the therapeutic effects on DMD through both cell-based and non-cell based mechanisms. In this study, we proposed that Myogenic Progenitor Cells from Induced Pluripotent Stem Cells (iPSC-MPCs) would be more effective in repairing muscle damage caused by muscular dystrophy. Methods and results: Mouse iPSCs were cultured in myogenic differentiation culture medium and the MPCs were characterized using Reverse Transcription Polymerase Chain Reaction (RT-PCR) and flow cytometry. iPSCs were successfully converted into MPCs, as evidenced by the distinct expression of myogenic genes and cell surface markers. The muscle injury was induced in tibialis muscle of mdx mouse by cardiotoxin injection, and the iPSC-MPCs were then engrafted into the damage site. Firefly luciferase expression vector was transduced into iPSC-MPCs and the in vivo bioluminescence imaging analysis revealed that these progenitor cells survived even at 30-days post transplantation. Importantly, histological analysis revealed that the central nuclei percentage, as well as fibrosis, was significantly reduced in the iPSC-MPCs treated muscle. In addition,the transplantation of progenitor cells restored the distributions of dystrophin and nicotinic acetylcholine receptors together with up-regulation of pair box protein 7(Pax7), a myogenic transcription factor. Conclusion: iPSCs-derived MPCs exert strong therapeutic effects on muscular dystrophy by restoring dystrophin expression and acetylcholine receptor distribution.

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