Perivascular cell contribution to skeletal muscle repair following physiological injury

PURPOSE: We have previously demonstrated that muscle-derived mesenchymal stem cells (MSCs; Sca-1+CD45-) accelerate Pax7+ satellite cell expansion and fiber repair during the initial stages of eccentric exercise training in mice. MSCs are a heterogeneous population of perivascular stromal cells, including but not limited to, pericytes, fibroadipogenic progenitor cells, and smooth muscle cells. Therefore, the purpose of this study was to examine the specific contribution of muscle-derived pericytes (CD146+CD45-CD31- or CD146+Lin-) to skeletal muscle repair following physiological injury. METHODS: Adult male wild type mice received bilateral intramuscular injection of pericytes 24 hr after a single bout of resistance exercise initiated by electrical stimulation of the sciatic nerve (n=5-6/group). Mice were sacrificed 4 days post-stimulation and the tibialis anterior muscles were analyzed for markers of damage (IgG+ myofibers, collagen), inflammation (CD11+ cells), and repair (fiber CSA, CLN+ fibers, myonuclei content). To determine the impact of the pericyte secretome on myoblast expansion and myotube development, CD146+Lin- pericytes were isolated from adult male wild type mouse skeletal muscle via enzymatic digestion and FACS. Following 12 days of recovery in culture, isolated pericytes were subjected to strain (10%, 1 Hz) for 1 hr using a Flexercell Strain unit. Conditioned media (CM) was collected from strained (CM-S) or unstrained (CM-NS) pericytes 24 hr later and applied to C2C12 myoblasts for up to 72 hr. RESULTS: Pericyte transplantation following electrical stimulation inhibited inflammation based on CD11b+ quantity and recovered the capillary-to-fiber ratio (P<0.05). The application of CM-S simultaneously reduced C2C12 quantity and increased myotube formation compared to CM-NS (P<0.05). CONCLUSION: The results from this study suggest that CD146+Lin- pericytes contribute to skeletal muscle repair after physiological injury.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Kinesiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2020

Author dc:creator

• Garcia, Gabriela

Contributors dc:contributor

• Boppart, Marni D
• Burd, Nicholas A

• pericytes
• repair
• injury.

Statement dc:rights

• Copyright 2020 Gabriela Garcia

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/108298

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/108298