Adipose Tissue-Derived Stromal Cells in Matrigel Impact the Regeneration of Severely Damaged Skeletal Muscles

Abstract

In case of large injuries of skeletal muscles the pool of endogenous stem cells, i.e., satellite cells, might be not sufficient to secure proper regeneration. Such failure in reconstruction is often associated with loss of muscle mass and excessive formation of connective tissue. Therapies aiming to improve skeletal muscle regeneration and prevent fibrosis may rely on the transplantation of different types of stem cell. Among such cells are adipose tissue-derived stromal cells (ADSCs) which are relatively easy to isolate, culture, and manipulate. Our study aimed to verify applicability of ADSCs in the therapies of severely injured skeletal muscles. We tested whether 3D structures obtained from Matrigel populated with ADSCs and transplanted to regenerating mouse gastrocnemius muscles could improve the regeneration. In addition, ADSCs used in this study were pretreated with myoblasts-conditioned medium or anti-TGFβ antibody, i.e., the factors modifying their ability to proliferate, migrate, or differentiate. Analyses performed one week after injury allowed us to show the impact of 3D cultured control and pretreated ADSCs at muscle mass and structure, as well as fibrosis development immune response of the injured muscle.

Beneficial Effect of IL-4 and SDF-1 on Myogenic Potential of Mouse and Human Adipose Tissue-Derived Stromal Cells

“…Moreover, in the case of mADSCs we also observed their participation in myofiber formation, which was significantly enhanced by IL-4 or combined IL-4 and SDF-1 treatment. Recently, we showed that also other factors, such as silencing of TGFβ signaling, combined with mADSCs can significantly improve muscle repair-again also by modulating immune response [76]. Thus, our results support the thesis that application of ADSCs could be beneficial for skeletal muscle tissue repair.…”

“…As far as ADSCs are concerned, they were shown to be able to participate in the regeneration of skeletal muscles of mdx mice [ 75 ]. However, even if MSCs were not involved in the generation of myofibers, their presence in the muscle was shown by us [ 76 ] and also others (e.g., [ 77 , 78 , 79 ]) to be beneficial for its regeneration due to their immunomodulatory function.…”

Injectable Gel Form of a Decellularized Bladder Induces Adipose-Derived Stem Cell Differentiation into Smooth Muscle Cells In Vitro

“…Matrigel was used as reference gel because it contains growth factors that promote proliferation and/or differentiation [ 29 ]. In fact, evidence that 3D cultures of cells on Matrigel could be beneficial for proliferation and/or differentiation has been reported [ 51 ]. For example, differentiation of myoblasts cultured in Matrigel was shown to be improved.…”

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

“…Many lines of evidence suggest that the paracrine action of MSCs is responsible for their beneficial impact at the tissue regeneration and may be enhanced by the application of selected cytokines or growth factors. Such beneficial action of ADSCs was also documented for skeletal muscles by us [12] and also by others [47,48]. Taking these arguments into consideration, we decided to utilize ADSCs in further analyses.…”

“…Thus, successful reconstruction of the extracellular environment of new muscle fibers is one of the most important factors determining the further condition of the tissue and many different strategies are currently used to deal with this issue. Among them are those aiming to modify extracellular environment, for example by inhibiting or activating factors crucial for the regeneration (e.g., [12,13]), or by using various cell populations, as we did in the current study. Nevertheless, the differences between fast-and slow-twitch muscles have to be taken into consideration while assessing the prognosis of the regeneration outcome.…”