Skeletal Muscle Regeneration by the Exosomes of Adipose Tissue-Derived Mesenchymal Stem Cells

Seong-Eun Byun,Hyung Kyung Kim,Soonchul Lee,Sungmoon Park,Seongmin Cho,Changgon Sim,Yoonhui Chung,Do Kyung Kim

doi:10.3390/cimb43030104

Abstract

Profound skeletal muscle loss can lead to severe disability and cosmetic deformities. Mesenchymal stem cell (MSC)-derived exosomes have shown potential as an effective therapeutic tool for tissue regeneration. This study aimed to determine the regenerative capacity of MSC-derived exosomes for skeletal muscle regeneration. Exosomes were isolated from human adipose tissue-derived MSCs (AD-MSCs). The effects of MSC-derived exosomes on satellite cells were investigated using cell viability, relevant genes, and protein analyses. Moreover, NOD-SCID mice were used and randomly assigned to the healthy control (n = 4), muscle defect (n = 6), and muscle defect + exosome (n = 6) groups. Muscle defects were created using a biopsy punch on the quadriceps of the hind limb. Four weeks after the surgery, the quadriceps muscles were harvested, weighed, and histologically analyzed. MSC-derived exosome treatment increased the proliferation and expression of myocyte-related genes, and immunofluorescence analysis for myogenin revealed a similar trend. Histologically, MSC-derived exosome-treated mice showed relatively preserved shapes and sizes of the muscle bundles. Immunohistochemical staining revealed greater expression of myogenin and myoblast determination protein 1 in the MSC-derived exosome-treated group. These results indicate that exosomes extracted from AD-MSCs have the therapeutic potential for skeletal muscle regeneration.

Highlights

The skeletal muscle, accounting for 30–40% of the total body weight [1], is important as a facilitator of physical activity by generating force and as a paracrine or endocrine organ affecting the bones and the body’s metabolism [2]
Mesenchymal stem cells (MSCs) are an attractive alternative treatment modality in tissue regeneration because they can supplement the shortage of cells
For the growth and differentiation of Human skeletal muscle satellite cells (HSkMSCs), the cells were cultured in skeletal muscle cell growth medium until they reached approximately 60%–80% confluence, and the medium was replaced with skeletal muscle cell differentiation medium supplemented with DMEM, 2% horse serum (HyClone), and 1% penicillin–streptomycin

Summary

Introduction

The skeletal muscle, accounting for 30–40% of the total body weight [1], is important as a facilitator of physical activity by generating force and as a paracrine or endocrine organ affecting the bones and the body’s metabolism [2]. Several pharmacologic agents, including myostatin inhibitors and androgenic hormone derivatives, have been used in attempts to regenerate the skeletal muscle [3,4,5]. Despite the promising results of a few trials [6,7], the lack of functional improvement and unexpected complications has prevented the clinical use of these drugs in muscle regeneration [3,4,5]. Cell-based regenerative approaches are urgently needed for therapy of skeletal muscle damage. If the muscle is severely and extensively injured, the number of local endogenous cells is often not adequate to restore tissue continuity or function in the defect [8]. MSCs can differentiate into many cell types, including osteoblasts, chondrocytes, adipocytes, and myoblasts [9]

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