Anti-necroptotic effects of human Wharton’s jelly-derived mesenchymal stem cells in skeletal muscle cell death model via secretion of GRO-α

Human mesenchymal stem cells (hMSCs) have therapeutic applications and potential for use in regenerative medicine. However, the use of hMSCs in research and clinical medicine is limited by a lack of information pertaining to their donor-specific functional attributes. In this study, we compared the characteristics of same-donor derived placenta (PL) and Wharton’s jelly (WJ)-derived hMSCs, we also compared their mechanism of action in a skeletal muscle disease in vitro model. The effects of GRO-α were also investigated in a Duchenne muscular dystrophy (DMD) mouse model. The same-donor-derived hWJ- and hPL-MSCs exhibited typical hMSC characteristics. GRO-α was differentially expressed in hWJ- and hPL-MSCs. However, when the secretion of GRO-α was considered, hWJ-MSCs displayed a higher ability to inhibit necroptosis in skeletal muscle cells than hPL-MSCs. This demonstrates the anti-necroptotic therapeutic effect of GRO-α in the skeletal muscle cell death model. Furthermore, considering their potential to inhibit necroptosis in skeletal muscle cells, hWJ-MSCs and the derived GRO-α are novel treatment options for skeletal muscle diseases such as DMD. To identify the secreted anti-necroptosis soluble factor from hWJ-MSCs, the conditioned media from each sample group, comprising hWJ- and hPL-MSCs from the same donor co-cultured with C2C12 cells, were analyzed using antibody arrays. We collected the conditioned media from the following groups to perform the array: C2C12 alone, hWJ-MSCs alone (A, B, C), hPL-MSCs alone (A, B, C), and C2C12 cells co-cultured with hWJ-MSCs (A, B, C), or hPL-MSCs (A, B, C). To identify the secreted anti-necroptosis soluble factor from hWJ-MSCs, the conditioned media from each sample group, comprising hWJ- and hPL-MSCs from the same donor co-cultured with C2C12 cells, were analyzed using antibody arrays.