Summary

Acellular Stem Cell Derivatives could become a new and effective therapy for the Treatment of Muscle Injuries

Abstract

Introduction

Acellular Stem Cell Derivatives (ASCD) have demonstrated anti-inflammatory and anti-fibrinolytic properties, hence they have a biological potential in the healing process of muscle injuries.

Purpose

To evaluate the effect of ASCD over the healing process in an animal muscle injury model.

Hypothesis

The local administration of ASCD favors muscle repair, because it decreases fibrotic tissue and increases the amount of regenerative muscle fibers.

Methods

Experimental in-vivo study in 52 male mice (age: 4-6 months). A complete mid-section in the right quadriceps was done in all the cases. Left quadriceps were left as a control group without intervention (group 5). Alpha-Mem, the same culture medium where the cells are cultivated, was used as the intervened control group and 3 different doses of ASCD were tested (low, intermediate and high). The interventions were locally administrated in an acute muscle injury (A=just after muscle section) or chronic muscle injury (C=14 days after muscle section). The mice were randomly assigned to the following intervention groups:
- 1A y 1C (control, n=10): Alpha-Mem 50ul.
- 2A y 2C (ASCD low dose, n=14): ASCD 10ul.
- 3A y 3C (ASCD intermediate dose, n=14): ASCD 25ul.
- 4A y 4C (ASCD high dose, n=14): ASCD 50ul.

All the animals were sacrificed 4 weeks after the muscle injury and a macroscopic evaluation was done. The samples were then histologically analyzed by a blind pathologist. Statistical analysis included the Kruskal-Wallis test (p<0.05) and an 80% of statistical power was considered.

Results

Macroscopic evaluation: group 4C presented significantly less atrophy and fibrosis than the other intervened groups (p=0.0363; p=0.0001). There were no significant differences for muscle mass and volume between groups 4C and 5 (non-intervened muscle) (p=0.454; p=0,343). All other groups presented significantly less mass and volume than group 5.
Histologic analysis: group 4C presented significantly less fibrosis than the other intervened groups (p=0.0004).

Conclusion

In this model, the local infiltration of high dose ASCD 14 days after the muscle injury, favored the healing process by decreasing muscle atrophy and fibrotic tissue.