Contribution of minced muscle graft progenitor cells to muscle fiber formation after volumetric muscle loss injury in wild-type and immune deficient mice.

Benjamin T Corona,Sarah M Greising,Catherine L Ward,Beth E P Henderson

doi:10.14814/phy2.13249

Benjamin T Corona, Sarah M Greising + Show 2 more

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https://doi.org/10.14814/phy2.13249

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Abstract

Volumetric muscle injury (VML) causes an irrecoverable loss of muscle fibers, persistent strength deficits, and chronic disability. A crucial challenge to VML injury and possible regeneration is the removal of all of the in situ native elements necessary for skeletal muscle regeneration. Our first goal was to establish a reliable VML model in the mouse tibialis anterior (TA) muscle. In adult male wild‐type and nude mice, a non‐repaired ≈20% VML injury to the TA muscle resulted in an ≈59% loss in nerve evoked muscle strength, ≈33% loss in muscle mass, and ≈29% loss of muscle fibers at 28 day post‐injury. Our second goal was to investigate if minced muscle grafts (≈1 mm3 tissue fragments) promote recovery of muscle fibers after VML injury and to understand if the graft‐derived progenitor cells directly contribute to fiber regeneration. To assess donor cell contribution, donor muscle tissue was derived from UBC‐GFP mice in a subset of experiments. Minced grafts restored ≈34% of the lost fibers 28 days post‐injury. The number of GFP + fibers and the estimated number of regenerated fibers were similar, regardless of host mouse strain. The muscle tissue regeneration promoted by minced grafts did not improve TA muscle strength at this time post‐injury. These findings demonstrate the direct contribution of minced muscle graft‐derived myogenic stem/progenitor cells to recovery of muscle fibers after VML injury and signify the utility of autologous myogenic stem cell therapies for this indication.

Highlights

Insufficient recovery of skeletal muscle strength following orthopedic injury contributes to chronic disability and the estimated ~$400 Billion economic impact of trauma in the United States annually (Bosse et al 2002; MacKenzie et al 2005; Corso et al 2006)
The nude mice weighed significantly more than the wildtype mice at surgery and sacrifice, for each strain there were no differences in body weights among cage control, no repair, and minced graft repair groups (Table 1)
Given the dearth of muscle fiber regeneration typically observed in whole and partial (i.e., volumetric muscle loss (VML)) muscle ablation models when devitalized or acellular biological scaffolds are implanted (Ghins et al 1984, 1985, 1986; Schultz et al 1986; Corona et al 2013b; Garg et al 2014b; Aurora et al 2015), the current findings suggest that co-delivery of a myogenic stem cell source is necessary to recover muscle fiber number after VML injury

Summary

Introduction

Insufficient recovery of skeletal muscle strength following orthopedic injury contributes to chronic disability and the estimated ~$400 Billion economic impact of trauma in the United States annually (Bosse et al 2002; MacKenzie et al 2005; Corso et al 2006). The partial traumatic ablation of skeletal muscle, or volumetric muscle loss (VML) injury, occurs frequently in civilian and military trauma (Papakostidis et al 2011; Corona et al 2015). This muscle injury is challenging to regenerate due to the removal of all of the in situ native elements necessary for skeletal muscle regeneration (e.g., basal lamina and satellite cells) (Corona et al 2016). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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