Forced expression of CD200 improves the differentiation capability and immunoregulatory functions of mesenchymal stromal cells
- 226 Downloads
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).
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.
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.
KeywordsAdipogenesis CD200 Chondrogenesis Immune regulation Mesenchymal stromal cells Osteogenesis
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (Grant Nos. 2015R1A2A2A04002756 and 2018R1A2B2006820). It was also supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (Grant Nos. 2010-0008762, 2014R1A1A3054664).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Payne NL, Dantanarayana A, Sun G, Moussa L, Caine S, McDonald C, Herszfeld D, Bernard CC, Siatskas C (2012) Early intervention with gene-modified mesenchymal stem cells overexpressing interleukin-4 enhances anti-inflammatory responses and functional recovery in experimental autoimmune demyelination. Cell Adhes Migr 6(3):179–189CrossRefGoogle Scholar
- Pietilä M, Lehtonen S, Tuovinen E, Lähteenmäki K, Laitinen S, Leskelä HV, Nätynki A, Pesälä J, Nordström K, Lehenkari P (2012) CD200 positive human mesenchymal stem cells suppress TNF-alpha secretion from CD200 receptor positive macrophage-like cells. PLoS ONE 7(2):e31671CrossRefPubMedPubMedCentralGoogle Scholar
- Xu L, Liu Y, Sun Y, Wang B, Xiong Y, Lin W, Wei Q, Wang H, He W, Wang B, Li G (2017) Tissue source determines the differentiation potentials of mesenchymal stem cells: a comparative study of human mesenchymal stem cells from bone marrow and adipose tissue. Stem Cell Res Ther 8(1):275CrossRefPubMedPubMedCentralGoogle Scholar