Clonal Isolation of Muscle-Derived Cells Capable of Enhancing Muscle Regeneration and Bone Healing

By J. Lee, Zhuqing Qu-Petersen, B. Cao, S. Kimura, R. Jankowski, J. Cummins, A. Usas, Charley Gates, P. Robbins, A. Wernig and 1 more. Journal of Cell Biology, 2000

671 citations recorded by the source corpus.

Several recent studies suggest the isolation of stem cells in skeletal muscle, but the functional properties of these muscle-derived stem cells is still unclear. In the present study, we report the purification of muscle-derived stem cells from the mdx mouse, an animal model for Duchenne muscular dystrophy. We show that enrichment of desmin+ cells using the preplate technique from mouse primary muscle cell culture also enriches a cell population expressing CD34 and Bcl-2. The CD34+ cells and Bcl-2+ cells were found to reside within the basal lamina, where satellite cells are normally found. Clonal isolation and characterization from this CD34+Bcl-2+ enriched population yielded a putative muscle-derived stem cell, mc13, that is capable of differentiating into both myogenic and osteogenic lineage in vitro and in vivo. The mc13 cells are c-kit and CD45 negative and express: desmin, c-met and MNF, three markers expressed in early myogenic progenitors; Flk-1, a mouse homologue of KDR recently identified in humans as a key marker in hematopoietic cells with stem cell-like characteristics; and Sca-1, a marker for both skeletal muscle and hematopoietic stem cells. Intramuscular, and more importantly, intravenous injection of mc13 cells result in muscle regeneration and partial restoration of dystrophin in mdx mice. Transplantation of mc13 cells engineered to secrete osteogenic protein differentiate in osteogenic lineage and accelerate healing of a skull defect in SCID mice. Taken together, these results suggest the isolation of a population of muscle-derived stem cells capable of improving both muscle regeneration and bone healing.

Subfields: Biomedical Engineering, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/7923e3343953eafd95015ff91d8079c0197d38b7

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Citations in the corpus

Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF and bone morphogenetic protein-4. (2002, methodology): “The MDSCs (MC13 clone) were isolated and cultured as previously described (10).”
Myogenic satellite cells: physiology to molecular biology. (2001, background): “88, 177), the glycoprotein Leu-19 (94, 162), the anti-apoptotic factor Bcl-2 (106, 123), CD34 (9), and interferon regulatory factor-2, which is a transcription factor that mediates VCAM-1 expression in skeletal muscle (89).”
The Skeletal Muscle Satellite Cell: The Stem Cell That Came in From the Cold (2006, background): “This effectively resolved the problem first noted by Lewis and Lewis (1917) that myofibers seemed to increase in size and in content of nuclei in the absence of any observable nuclear division within the myofiber.”
Satellite cells and the muscle stem cell niche. (2013, background): “A series of studies have demonstrated that a distinct cell population, termed muscle-derived stem cells (MDSCs), can be isolated from skeletal muscles based on their weak adhesion characteristics and long-term proliferation behaviors in culture (247, 294, 421, 422).”
Adult mesenchymal stem cells for tissue engineering versus regenerative medicine (2007, background): “Cell preparations from both adipose and muscle tissue exhibit MSC-like differentiation properties and distinctive cell surface markers (Lee et al., 2000; Katz et al., 2005).”