Date of Graduation

5-2019

Document Type

Thesis

Degree Name

Bachelor of Science

Degree Level

Undergraduate

Department

Health, Human Performance and Recreation

Advisor/Mentor

Washington, Tyrone

Committee Member/Reader

Gray, Michelle

Committee Member/Second Reader

Greene, Nicholas

Abstract

Background: Volumetric muscle loss (VML) is defined as a permanent loss of muscle tissue and function. Recent studies have used biomedical interventions such as decellularized matrices and autologous repair to enhance muscle regeneration of these injuries. Furthermore, exercise has also been shown to aid in the regenerative response. Biomedical interventions and physical activity help to attenuate severe fibrosis as well as encourage satellite cell activation in VML models. However, it is not known whether these interventions affect muscle tissue distal to the injury site. Purpose: The purpose of this study was to evaluate the effects of autologous muscle grafting and exercise on satellite cell mechanics distal to the defect site. Methodology: Male, Sprague-Dawley rats were randomly assigned to either exercised (wheel access, WA) or sedentary (cage access, CA) groups and were further divided into 2 and 8 week groups (2WA, 8WA, 2CA, 8CA). A muscle biopsy punch was utilized to cause a defect in the left tibialis anterior (TA) equivalent to 20% of the TA by weight. The defect tissue was then sutured into the site, and the experimental groups continued their respective activities. The TA was harvested 2 and 8 weeks post-VML. Uninjured TA tissue of the VML muscle was isolated, RNA was extracted, cDNA synthesized, and quantitative PCR was performed. Quantitative PCR determined the gene expression of IGF-1, MyoD, MyoG, Ki67, and TGF-β1. Results: There was no significant difference in the BW at surgery (p>0.05). There was a main effect of exercise to decrease terminal BW by ~6% and ~5% in the 2-week and 8-week rats, respectively (p<0.05). There was a main effect of time to increase BW ~7% and ~8% in the sedentary and exercise rats, respectively (p<0.05). The % BW difference saw similar results as terminal BW with main effects of time and exercise to increase (~ 42-80%) and decrease (~22-33%) the % body weight difference, respectively. There was a main effect of time to decrease Ki67 mRNA expression (p<0.05). There were no significant differences in mRNA abundance of MyoD, MyoG, IGF-1 or TGF-β1. Discussion: Based on the current findings, there are no indications that satellite cell activation is initiated in uninjured tissue distal to the injury 2- and 8- weeks post-injury. However, acute elevation of Ki67 may indicate proliferation of cells other than satellite cells such as fibroblasts which have been shown to be rapidly increased in the presence of VML injuries.

Keywords

myogenic regulatory factors; growth factors; skeletal muscle regeneration

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