Implantation of autologous cells in minced and devitalized rat skeletal muscles

Abstract

Triceps surae of 3 week-old female Wistar rats were minced and orthotopically autografted. Thirty days later, the regenerates developed a force of 314 +/- 58 mN during an isometric maximal tetanus and the maximal area of the muscle tissue was 3.2 +/- 0.5 mm2 (n = 9) in a cross-section. At 60 days, their mean maximal isometric force was increased (1159 +/- 367 mN) as also were their maximal muscle cross-section area (6.8 +/- 0.7 mm2;n = 6). If the minces were devitalized by a freeze and thaw procedure, the regenerates neither contracted under electrical stimulation nor contained any muscle fibre. If devitalized minces were seeded with myogenic cells isolated from the contralateral triceps surae, orthotopically autografted and allowed to regenerate for 30 days, the regeneration was weak: 46 +/- 14 mN of force, 1.2 +/- 0.3 mm2 of muscle area in minces devitalized by cold (n = 7) and 23 +/- 8 mN of force, 0.2 +/- 0.1 mm2 of muscle area in minces devitalized by cold supplemented by heat (n = 8). If viable minces were seeded with myogenic cells, there was no improvement in the extent of regeneration: 275 +/- 83 mN of force, 2.0 +/- 0.6 mm2 of muscle area at 30 days (n = 7) and 738 +/- 191 mN of force, 5.6 +/- 0.9 mm2 of muscle area at 60 days (n = 5). Consequently, although it is possible to induce regeneration by grafting myogenic cells into a devitalized mince, this procedure has no effect when applied to a viable mince.

Enhancement of skeletal muscle regeneration

“…Numerous studies have shown that grafted satellite cells, often expanded in culture, participate in myogenesis in both normal (Jones, 1979;Lipton and Schultz, 1979;Alameddine et al, 1989) and myopathic (Karpati, 1989;Law et al, 1990;Morgan et al, 1990;Huard et al, 1991) host muscle, but there has been little interest in the use of cell grafts to improve regeneration. In the only such study of which we are aware, Ghins et al (1986) found that although satellite cells isolated from the contralateral leg could support regeneration in devitalized mince, the cells did not enhance regeneration when added to viable mince. The cells were not purified nor expanded in culture, which may account for the lack of effect as compared with the present study.…”

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

“…Given the dearth of muscle fiber regeneration typically observed in whole and partial (i.e., VML) muscle ablation models when devitalized or acellular biological scaffolds are implanted (Ghins et al. , , ; Schultz et al. ; Corona et al.…”

“…Specifically, investigations in which minced muscle grafts were manipulated to vary the level of muscle stem cell delivery indicated a corresponding magnitude of muscle fiber regeneration (Ghins et al. , , ). Notably, when only devitalized grafts were implanted (i.e., no muscle progenitor/stem cells), no muscle fiber regeneration was observed, unless freshly isolated or cultured muscle progenitor cells were co‐delivered.…”

“…Multiple investigations performed in rats indicated that the muscle progenitor cells were primarily derived from the minced grafts (Ghins et al. , , ). In these studies, de novo tissue formation was lost if the minced grafts were devitalized and partially restored with delivery of isolated myogenic progenitors (Ghins et al.…”

“…In these studies, de novo tissue formation was lost if the minced grafts were devitalized and partially restored with delivery of isolated myogenic progenitors (Ghins et al. , ). Recently, the inability of devitalized minced grafts to promote muscle fiber regeneration in VML injured muscle has been reported (Garg et al.…”