Forced expression of CD200 improves the differentiation capability and immunoregulatory functions of mesenchymal stromal cells

Biotechnol Lett. 2018 Oct;40(9-10):1425-1433. doi: 10.1007/s10529-018-2561-0. Epub 2018 May 9.

Abstract

Objective: In order to identify specific mesenchymal stromal cell (MSC) populations with enhanced therapeutic efficacy, we evaluated the functional changes associated with the stable expression of CD200, which is associated with immune regulatory function and osteogenic differentiation, in human bone marrow-derived MSCs (CD200/MSCs).

Results: We detected significantly greater osteogenesis and chondrogenesis in CD200/MSCs than in mock-transfected MSCs. In addition, the immune regulatory function of MSCs in mixed lymphocyte reactions was enhanced by CD200 gene transfection. In CD200/MSCs, the secretion of inflammatory cytokines, i.e., IL-6 and IL-8, was reduced, and levels of the anti-inflammatory factors IL-10, FOXP3, and indoleamine 2,3-dioxygenase 1 were elevated. Finally, CD200 transfection increased the stemness of MSCs, as evidenced by greater colony numbers in colony-forming unit fibroblast assays and analyses of NANOG and OCT-4 expression.

Conclusions: These results suggest that CD200/MSCs have therapeutic applications, and further in-depth research should focus on the development of a clinically applicable cell-based therapeutic strategy.

Keywords: Adipogenesis; CD200; Chondrogenesis; Immune regulation; Mesenchymal stromal cells; Osteogenesis.

MeSH terms

  • Antigens, CD / biosynthesis*
  • Bone Marrow Cells / physiology*
  • Cell Differentiation*
  • Cells, Cultured
  • Chondrogenesis
  • Gene Expression*
  • Humans
  • Immunologic Factors / metabolism
  • Mesenchymal Stem Cells / physiology*
  • Osteogenesis

Substances

  • Antigens, CD
  • Immunologic Factors
  • antigens, CD200