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Significance Mesenchymal stem or stromal cells (MSCs) offer great promise as potential therapies for cancers and other diseases. However, applications of MSCs for cancer therapy are hindered by their protumor potential under certain conditions, considerable donor variations, and limited expandability. Here we report generation of induced pluripotent stem cells (iPSC)-derived MSCs with same tumor homing capacity but much less protumor potential using a modified protocol with high derivation efficiency. Starting from iPSCs with almost unlimited expandability, the protocol can be readily scaled up to provide huge amounts of MSCs with uniform biological properties for multicenter evaluation, large animal experiments, and potential clinical trial. Moreover, therapeutic transgenes can be inserted into safe-harbor loci of iPSCs before derivation of MSCs to eliminate insertional mutation and guarantee stable expression of transgenes during prolonged expansion.

MSCs derived from iPSCs with a modified protocol are tumor-tropic but have much less potential to promote tumors than bone marrow MSCs