CD90- (Thy-1-) High Selection Enhances Reprogramming Capacity of Murine Adipose-Derived Mesenchymal Stem Cells

Abstract

Background. 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.Method. Murine ADSCs were isolated from B6 mice, sorted using a FACSAria cell sorter by selection ofCD90HiorCD90Lo, and then transduced with four standard factors (4F; Oct4, Sox2, Klf4, and c-Myc).Results. Unsorted,CD90Hi-sorted, andCD90Lo-sorted murine ADSCs were reprogrammed using standard 4F transduction.CD90HiADSCs showed increased numbers of alkaline phosphatase-positive colonies compared withCD90LoADSCs. The relative reprogramming efficiencies of unsorted,CD90Hi-sorted, andCD90Lo-sorted ADSCs were 100%, 116.5%, and 74.7%, respectively.CD90Hicells were more responsive to reprogramming.Conclusion.CD90HiADSCs had greater reprogramming capacity thanCD90LoADSCs, suggesting that ADSCs have heterogeneous subpopulations. Thus,CD90Hiselection presents an effective strategy to isolate a highly suppressive subpopulation for stem cell-based tolerance induction therapy.