Journal
STEM CELL RESEARCH & THERAPY
Volume 8, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s13287-017-0589-z
Keywords
Bone marrow mononuclear cells; Volumetric muscle loss; Skeletal muscle; Regenerative medicine; Minced muscle graft; Musculoskeletal trauma
Funding
- United States Army Medical Research and Materiel Command, Clinical and Rehabilitative Medical Research Program [C_003_2015_USAISR]
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Background: The delivery of alternative myogenic cell sources to enhance the efficacy of minced muscle grafts (MG) for the treatment of volumetric muscle loss (VML) injuries is a promising strategy to overcome the demand on muscle-derived donor tissue that currently limits the translation of this therapy. Methods: Using a rat model of VML, bone marrow mononuclear cells (BMNCs) were evaluated for their ability to directly contribute to de novo muscle fiber regeneration by transplanting MG in a collagen carrier at a dose of 50% of the VML injury both with and without concomitant delivery of 5 million BMNCs derived via density gradient centrifugation from the bone marrow of a syngeneic green fluorescent protein (GFP)(+) donor. Results: Histological, molecular, and functional analyses revealed that BMNCs can engraft with co-delivered MG and contribute to nascent myofiber, but do so at a low magnitude without resulting in significant changes to transcription of key myogenic genes or gains in whole muscle force generation relative to MG alone. Conclusion: As such, co-delivery of BMNCs with MG is a promising treatment paradigm to VML that will require further investigation to identify the phenotype and therapeutic dosing of the bone marrow-derived cell populations which engraft most efficiently.
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