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

PLoS One. 2024 Dec 2;19(12):e0313693. doi: 10.1371/journal.pone.0313693. eCollection 2024.

Abstract

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 same-donor-derived hWJ- and hPL-MSCs exhibited typical hMSC characteristics. However, GRO-α was differentially expressed in hWJ- and hPL-MSCs. hWJ-MSCs, which secreted a high amount of GRO-α, 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, GRO-α also exhibited the anti-necroptotic effect in a Duchenne muscular dystrophy (DMD) mouse model. 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.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Humans
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • Muscle, Skeletal* / metabolism
  • Muscular Dystrophy, Duchenne / metabolism
  • Muscular Dystrophy, Duchenne / pathology
  • Muscular Dystrophy, Duchenne / therapy
  • Necroptosis* / drug effects
  • Placenta / cytology
  • Placenta / metabolism
  • Pregnancy
  • Wharton Jelly* / cytology

Grants and funding

This study was supported by grants awarded by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) (HR22C1363 and HI14C3484), and funded by the Ministry of Health & Welfare, Republic of Korea. This work was supported by the Collabo R&D between Industry, Academy, and Research Institute (S3098634) funded by the Ministry of SMEs and Startups (MSS, Korea), by grants from the National Research Foundation of Korea (2021R1F1A1064060 and 2021R1F1A1062366), and supported by Korean Fund for Regenerative Medicine funded by Ministry of Science and ICT, and Ministry of Health and Welfare (RS-2022-00060268, RS-2023-0023069, Republic of Korea), and by Samsung Medical Center (SMO1220041). The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.