Abstract
Mesenchymal stem cells (MSCs), including adipose tissue-derived mesenchymal stem cells(ADSC), are multipotent and can differentiate into various cell types possessing unique immunomodulatory features. Several clinical trials have demonstrated the safety and possible efficacy of MSCs in organ transplantation. Thus, stem cell therapy is promising for tolerance induction. In this study, we assessed the reprogramming capacity of murine ADSCs and found that CD90(Thy-1), originally discovered as a thymocyte antigen, could be a useful marker for cell therapy. Murine ADSCs were isolated from B6 mice, sorted by selection of CD90Hi or CD90Lo, and then transduced with four standard factors (Oct4, Sox2, Klf4, and c-Myc). Among unsorted, CD90Hi-, and CD90Lo- murine ADSCs, reprogrammed CD90Hi ADSCs showed increased numbers of alkaline phosphatase-positive colonies compared with reprogrammed CD90Lo ADSCs. The relative reprogramming efficiencies of unsorted, CD90Hi-sorted, and CD90Lo-sorted ADSCs were 100%, 116.5%, and 74.7%, respectively. CD90Hi cells were more responsive to reprogramming. CD90Hi ADSCs had greater reprogramming capacity than CD90Lo ADSCs, suggesting that ADSCs have heterogeneous subpopulations. Thus, CD90Hi selection presents an effective strategy to isolate a highly suppressive subpopulation for stem cell-based tolerance induction therapy.
