A cost-effective method to prepare mesenchymal stem cells (MSCs) from human pluripotent stem cells

Induced mesenchymal stem cells (iMSCs) derived from human pluripotent stem cells (hPSCs) offer several advantages over tissue-derived mesenchymal stem cells (MSCs), including unlimited donor expansion, minimal batch-to-batch variation, a controllable pathogen microbiota, and the potential for large-scale production. However, producing iMSCs has several challenges, such as complex differentiation protocols, high costs, and poor reproducibility. Therefore, more effective differentiation methods are needed. In this study, iMSC differentiation was induced based on the classical method of using TGF-β signaling inhibitors. We discovered that due to the differences in the adhesiveness of gelatin to different cells, target cells can be rapidly selected and further differentiated to obtain high-purity iMSCs. This approach is more straightforward and less cost-effective than previous methods, producing iMSCs with higher purity and greater yield. We revealed that the DGEA active motif in gelatin produced effects similar to those of gelatin, playing an essential role in iMSC differentiation. In summary, our differentiation method addresses many of the issues associated with classical industrialization iMSC differentiation protocols and provides valuable insights into the production of iMSCs for clinical translation.