We recently have used a modified preplate technique to isolate 3 populations of myogenic cells from normal mouse skeletal muscle based on their adhesion characteristics and proliferation behaviors. Although 2 of these populations display satellite cell characteristics, the third population consists of long_term proliferating (LTP) cells expressing hematopoietic stem cell markers. The stem cell characteristics of the LTP cells include the abilities to retain their phenotype for more than 30 passages in culture (self-renewal) and to differentiate into various lineages, including muscle, neural, osteogenic, and endothelial. The transplantation of the LTP cells, in contrast to satellite cell transplantation, significantly improved the efficiency of muscle regeneration and dystrophin delivery to dystrophic muscle. The overall goal of our proposed project is to further investigate important features of the LTP cells (i.e., sources and mechanisms involved with the improved transplantation capacity) that are paramount to their potential use in transplantation to improve muscle regeneration and deliver dystrophin to dystrophic muscle. In this project we will investigate potential sources of the LTP cells by determining their relationship to satellite cells and to the Side Population (SP) stem cells derived from skeletal muscle (Aim #1). We subsequently will investigate mechanisms by which the LTP cells display an improved transplantation capacity in skeletal muscle. We will evaluate the relative effects of the proliferation and differentiation kinetics of the cells (Aim #2) and determine the possibility that immune_privileged cell behavior also plays a role in the increased regenerative capacity of LTP cells in skeletal muscle (Aim #3). Analysis of the relative importance of the LTP cells' self-renewal and multipotent capabilities will shed light on the contribution of stem cell characteristics to the improved transplantation capacity in skeletal muscle (Aim #4). This project might increase our understanding of the basic biology of myogenic cell populations that display stem cell characteristics. This in turn may unveil new techniques to improve muscle regeneration in dystrophic or injured skeletal muscle via the transplantation of muscle-derived stem cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR049684-04
Application #
6944880
Study Section
Special Emphasis Panel (ZAR1-JRL-B (O1))
Program Officer
Nuckolls, Glen H
Project Start
2002-09-27
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
4
Fiscal Year
2005
Total Cost
$224,757
Indirect Cost
Name
Children's Hosp Pittsburgh/Upmc Health Sys
Department
Type
DUNS #
044304145
City
Pittsburgh
State
PA
Country
United States
Zip Code
15224
Baily, James E; Chen, William C W; Khan, Nusrat et al. (2016) Isolation of Perivascular Multipotent Precursor Cell Populations from Human Cardiac Tissue. J Vis Exp :
Chen, William C W; Baily, James E; Corselli, Mirko et al. (2015) Human myocardial pericytes: multipotent mesodermal precursors exhibiting cardiac specificity. Stem Cells 33:557-73
Lavasani, Mitra; Thompson, Seth D; Pollett, Jonathan B et al. (2014) Human muscle-derived stem/progenitor cells promote functional murine peripheral nerve regeneration. J Clin Invest 124:1745-56
Lavasani, Mitra; Pollett, Jonathan B; Usas, Arvydas et al. (2013) The microenvironment-specific transformation of adult stem cells models malignant triton tumors. PLoS One 8:e82173
Chen, Chien-Wen; Okada, Masaho; Proto, Jonathan D et al. (2013) Human pericytes for ischemic heart repair. Stem Cells 31:305-16
Saparov, Arman; Chen, Chien-Wen; Beckman, Sarah A et al. (2013) The role of antioxidation and immunomodulation in postnatal multipotent stem cell-mediated cardiac repair. Int J Mol Sci 14:16258-79
Zheng, Bo; Li, Guangheng; Chen, William C W et al. (2013) Human myogenic endothelial cells exhibit chondrogenic and osteogenic potentials at the clonal level. J Orthop Res 31:1089-95
Lavasani, Mitra; Gehrmann, Sebastian; Gharaibeh, Burhan et al. (2011) Venous graft-derived cells participate in peripheral nerve regeneration. PLoS One 6:e24801
Li, Guangheng; Zheng, Bo; Meszaros, Laura B et al. (2011) Identification and characterization of chondrogenic progenitor cells in the fascia of postnatal skeletal muscle. J Mol Cell Biol 3:369-77
Quintero, Andres J; Wright, Vonda J; Fu, Freddie H et al. (2009) Stem cells for the treatment of skeletal muscle injury. Clin Sports Med 28:1-11

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