Gene expression profile of immunoregulatory cytokines secreted from bone marrow and adipose derived human mesenchymal stem cells in early and late passages

Mol Biol Rep. 2020 Mar;47(3):1723-1732. doi: 10.1007/s11033-020-05264-2. Epub 2020 Feb 10.

Abstract

Mesenchymal Stem Cells (MSCs) have therapeutic potential in a variety of diseases; however, the safety and efficacy of their use remain ambiguous. Clinical applications of MSCs are under intensive investigation due to their immunomodulatory features and lack of immune reactivity. Therefore, having a clear perspective on the exact mechanisms underlying the regulation of cytokine secretion in different microenvironments seems crucially important.In the current study, samples from human bone marrow and adipose were collected, and peripheral blood mononuclear cells (PBMCs) were isolated and cultured in conventional medium. After MSC expansion, the cells from passage 3 (P3) and passage 9 (P9) were utilized to identify MSC cell surface markers and their differentiation capacity. The P3, P5, P7, and P9 cells were used for RNA extraction to qualify the expression of the main immunomodulatory cytokines IDO, VCAM-1, TGF-β, IL-6, IL-10, and PGE2 at mRNA levels. The results indicate that VCAM-1 expression in the subcultures was reduced in bone marrow-derived MSCs. After an increase in P5, P7, and P9, IL-6 expression was reduced. In adipose-derived MSCs, the mRNA levels of IL-10 in higher passages were decreased compared with P3; other studied cytokines had no significant changes in their expression levels in either bone marrow or adipose-derived MSCs. Based on these results, it can be concluded that a suitable source for MSCs in cell therapy with stable expression of main cytokines, even in higher subcultures, appears to be adipose-derived MSCs with the exception of IL-10 secretion.

Keywords: Adipose-derived MSCs; Bone marrow-derived MSCs; Inflammatory and anti-inflammatory cytokines; Passage number.

MeSH terms

  • Adipose Tissue / cytology*
  • Adult
  • Aged
  • Bone Marrow / metabolism*
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Cytokines / genetics*
  • Female
  • Gene Expression Profiling / methods*
  • Humans
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Middle Aged

Substances

  • Cytokines