Modulation of Stem Cells Differentiation and Myostatin as an Approach to Counteract Fibrosis in Muscle Dystrophy and Regeneration after Injury
Abstract
Muscle derived stem cells (MDSC) were isolated from the myostatin wild type mouse (Wt) the myostatin knock out mouse (Mst ko) and a DMD mouse model (mdx) and shown that: 1) Implants of Wt MDSC regenerate in vivo smooth muscle tissue and other cell types in injured or impaired tissue and correct the functional dysfunction created by the loss of these cells and myofibroblast generation and also convert into myofibers in skeletal muscle thus showing MDSC responsiveness to in vivo paracrine modulation of cell lineage. 2) Wt MDSC express an embryonic stem cell marker Oct-4 and cells positive for this marker were located in vivo in the skeletal muscle using a transgenic mouse model that detects Oct-4 expression with a reporter gene; 3) Wt and Mst ko MDSC were unexpectedly resistant to in vitro paracrine and autocrine modulation of myogenesis by effectors of the myostatin pathway but our previous results suggest that MDSC differentiation is responsive in vivo to factors in the tissue environment. 4) Myostatin pro-fibrotic role was shown in a multipotent cell line the C3H 10T1/2 and in vivo in stem cells in connective tissue thus confirming our proposal to counteract myostatin in MDSC or in the host tissue for the therapy of DMD.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2008
- Accession Number
- ADA484168
Entities
People
- Nestor F. Gonzalez
Organizations
- Charles R. Drew University of Medicine and Science