title: Mesenchymal progenitor cells derived from traumatized muscle enhance neurite growth.
abstract: The success of peripheral nerve regeneration is governed by the rate and quality of axon bridging and myelination that occurs across the damaged region. Neurite growth and the migration of Schwann cells is regulated by neurotrophic factors produced as the nerve regenerates, and these processes can be enhanced by mesenchymal stem cells (MSCs), which also produce neurotrophic factors and other factors that improve functional tissue regeneration. Our laboratory has recently identified a population of mesenchymal progenitor cells (MPCs) that can be harvested from traumatized muscle tissue debrided and collected during orthopaedic reconstructive surgery. The objective of this study was to determine whether the traumatized muscle-derived MPCs exhibit neurotrophic function equivalent to that of bone marrow-derived MSCs. Similar gene- and protein-level expression of specific neurotrophic factors was observed for both cell types, and we localized neurogenic intracellular cell markers (brain-derived neurotrophic factor and nestin) to a subpopulation of both MPCs and MSCs. Furthermore, we demonstrated that the MPC-secreted factors were sufficient to enhance in vitro axon growth and cell migration in a chick embryonic dorsal root ganglia (DRG) model. Finally, DRGs in co-culture with the MPCs appeared to increase their neurotrophic function via soluble factor communication. Our findings suggest that the neurotrophic function of traumatized muscle-derived MPCs is substantially equivalent to that of the well-characterized population of bone marrow-derived MPCs, and suggest that the MPCs may be further developed as a cellular therapy to promote peripheral nerve regeneration.
authors.affiliation: Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: Wesley M
authors.initials: WM
authors.lastname: Jackson
authors.forename: Peter G
authors.initials: PG
authors.lastname: Alexander
authors.forename: Jamie D
authors.initials: JD
authors.lastname: Bulken-Hoover
authors.forename: Jared A
authors.initials: JA
authors.lastname: Vogler
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Ji
authors.forename: Patricia
authors.initials: P
authors.lastname: McKay
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Nesti
authors.forename: Rocky S
authors.initials: RS
authors.lastname: Tuan
mesh_terms: D000818:Animals; D048430:Cell Shape; D002478:Cells, Cultured; D002642:Chick Embryo; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009132:Muscles / Q000473:pathology*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D009414:Nerve Growth Factors