IL-4 and SDF-1 Increase Adipose Tissue-Derived Stromal Cell Ability to Improve Rat Skeletal Muscle Regeneration

Abstract

Skeletal muscle regeneration depends on the satellite cells, which, in response to injury, activate, proliferate, and reconstruct damaged tissue. However, under certain conditions, such as large injuries or myopathies, these cells might not sufficiently support repair. Thus, other cell populations, among them adipose tissue-derived stromal cells (ADSCs), are tested as a tool to improve regeneration. Importantly, the pro-regenerative action of such cells could be improved by various factors. In the current study, we tested whether IL-4 and SDF-1 could improve the ability of ADSCs to support the regeneration of rat skeletal muscles. We compared their effect at properly regenerating fast-twitch EDL and poorly regenerating slow-twitch soleus. To this end, ADSCs subjected to IL-4 and SDF-1 were analyzed in vitro and also in vivo after their transplantation into injured muscles. We tested their proliferation rate, migration, expression of stem cell markers and myogenic factors, their ability to fuse with myoblasts, as well as their impact on the mass, structure and function of regenerating muscles. As a result, we showed that cytokine-pretreated ADSCs had a beneficial effect in the regeneration process. Their presence resulted in improved muscle structure and function, as well as decreased fibrosis development and a modulated immune response.

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

“…Gorecka et al showed that transplantation of AD-MSCs significantly improved functional muscle tissue regeneration in an injured muscle [17]. Furthermore, Zimowska et al reported that cytokine-pretreated AD-MSCs had a beneficial effect on skeletal muscle regeneration [34].…”

“…MSC therapeutic effects might be due to the secretion of bioactive factors in the extracellular vesicles [35]. Gorecka et al suggested that AD-MSC facilitates muscle regeneration by secreting factors involved in transient acceleration of skeletal muscle repair [34]. In this context, stem cell-derived exosomes have recently been introduced to regenerative medicine.…”

The Influence of Intervertebral Disc Microenvironment on the Biological Behavior of Engrafted Mesenchymal Stem Cells

“…IL-4 is another important anti-inflammatory cytokine in the body. Pretreatment with IL-4 can improve the migration ability of MSCs and the expression level of certain proteins, which has a beneficial effect on the regeneration process of MSCs [ 189 , 199 , 200 ].…”

Application of adipose-derived stem cells in treating fibrosis

“…Zimowska et al [ 32 ] studied whether ASCs treated with IL-4 and stromal derived factor-1 (SDF-1), both of which enhance skeletal muscle regeneration, had a better effect in promoting skeletal muscle regeneration. In vitro treatment of IL-4 and SDF-1 significantly enhanced ASCs proliferation and migration.…”

“…During muscle repair, fibrosis is a common adverse factor as it stiffens and weakens the healed muscle, depriving it of normal function. In vivo transplantation of ASCs into skeletal muscle injury models resulted in better muscle morphology under the microscope, with more regenerated myofibers and less collagen fiber deposition, through regulating immune responses[ 32 ]. It is worth noting that ASCs exhibited better regenerative effects than bone marrow-derived mesenchymal stem cells[ 43 ], providing evidence for choosing the most suitable cell type for muscle repair.…”