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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

Autologous minced muscle grafts partially restore muscle fiber number after repair of VML injury. TA muscles were harvested at 28 days post‐injury. (A) Representative whole TA muscle cross‐sections stained with Hematoxylin and Eosin are presented per mouse strain and experimental group. Scale bar = 400 μm. (B) Whole TA muscle fiber number plotted per mouse strain and experimental group (Sample Sizes [Wild Type, Nude]: Contralateral (9, 7), No Repair (4, 4), and Minced Graft (5, 4). Two‐way ANOVA demonstrated only a main effect of experimental group (P < 0.001) and not a main effect of mouse strain (P = 0.977) or an interaction (P = 0.965). *, <Contralateral; †<Minced Graft; P < 0.05.
© Copyright Policy - creativeCommonsBy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5392532&req=5

phy213249-fig-0001: Autologous minced muscle grafts partially restore muscle fiber number after repair of VML injury. TA muscles were harvested at 28 days post‐injury. (A) Representative whole TA muscle cross‐sections stained with Hematoxylin and Eosin are presented per mouse strain and experimental group. Scale bar = 400 μm. (B) Whole TA muscle fiber number plotted per mouse strain and experimental group (Sample Sizes [Wild Type, Nude]: Contralateral (9, 7), No Repair (4, 4), and Minced Graft (5, 4). Two‐way ANOVA demonstrated only a main effect of experimental group (P < 0.001) and not a main effect of mouse strain (P = 0.977) or an interaction (P = 0.965). *, <Contralateral; †<Minced Graft; P < 0.05.

Mentions: The total number of muscle fibers within cross‐sections derived from the midbelly (uninjured) or defect region was counted in uninjured (contralateral) and injured non‐repaired and autologous minced graft‐repaired TA muscles harvested 28 days post‐injury from wild‐type and nude mice. No significant differences between strains were observed. VML injury left unrepaired resulted a ≈29% decrease in the total number of TA muscle fibers (Fig. 1). Autologous minced graft repair of the VML injury promoted a ≈14% increase compared to non‐repaired muscles, leaving a residual ≈19% loss of muscle fibers compared to uninjured contralateral muscles.


Contribution of minced muscle graft progenitor cells to muscle fiber formation after volumetric muscle loss injury in wild ‐ type and immune deficient mice
Autologous minced muscle grafts partially restore muscle fiber number after repair of VML injury. TA muscles were harvested at 28 days post‐injury. (A) Representative whole TA muscle cross‐sections stained with Hematoxylin and Eosin are presented per mouse strain and experimental group. Scale bar = 400 μm. (B) Whole TA muscle fiber number plotted per mouse strain and experimental group (Sample Sizes [Wild Type, Nude]: Contralateral (9, 7), No Repair (4, 4), and Minced Graft (5, 4). Two‐way ANOVA demonstrated only a main effect of experimental group (P < 0.001) and not a main effect of mouse strain (P = 0.977) or an interaction (P = 0.965). *, <Contralateral; †<Minced Graft; P < 0.05.
© Copyright Policy - creativeCommonsBy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5392532&req=5

phy213249-fig-0001: Autologous minced muscle grafts partially restore muscle fiber number after repair of VML injury. TA muscles were harvested at 28 days post‐injury. (A) Representative whole TA muscle cross‐sections stained with Hematoxylin and Eosin are presented per mouse strain and experimental group. Scale bar = 400 μm. (B) Whole TA muscle fiber number plotted per mouse strain and experimental group (Sample Sizes [Wild Type, Nude]: Contralateral (9, 7), No Repair (4, 4), and Minced Graft (5, 4). Two‐way ANOVA demonstrated only a main effect of experimental group (P < 0.001) and not a main effect of mouse strain (P = 0.977) or an interaction (P = 0.965). *, <Contralateral; †<Minced Graft; P < 0.05.
Mentions: The total number of muscle fibers within cross‐sections derived from the midbelly (uninjured) or defect region was counted in uninjured (contralateral) and injured non‐repaired and autologous minced graft‐repaired TA muscles harvested 28 days post‐injury from wild‐type and nude mice. No significant differences between strains were observed. VML injury left unrepaired resulted a ≈29% decrease in the total number of TA muscle fibers (Fig. 1). Autologous minced graft repair of the VML injury promoted a ≈14% increase compared to non‐repaired muscles, leaving a residual ≈19% loss of muscle fibers compared to uninjured contralateral muscles.

View Article: PubMed Central - PubMed

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&nbsp;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&#8208;type and nude mice, a non&#8208;repaired &asymp;20% VML injury to the TA muscle resulted in an &asymp;59% loss in nerve evoked muscle strength, &asymp;33% loss in muscle mass, and &asymp;29% loss of muscle fibers at 28&nbsp;day post&#8208;injury. Our second goal was to investigate if minced muscle grafts (&asymp;1&nbsp;mm3 tissue fragments) promote recovery of muscle fibers after VML injury and to understand if the graft&#8208;derived progenitor cells directly contribute to fiber regeneration. To assess donor cell contribution, donor muscle tissue was derived from UBC&#8208;GFP mice in a subset of experiments. Minced grafts restored &asymp;34% of the lost fibers 28&nbsp;days post&#8208;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&#8208;injury. These findings demonstrate the direct contribution of minced muscle graft&#8208;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.

No MeSH data available.


Related in: MedlinePlus