Embryonic lineage-specific iPSC-derived mesenchymal stem/stromal cells exhibit different morphology and intrinsic functions

Mesenchymal stem/stromal cells (MSCs) have great potential in regenerative medicine owing to their multilineage differentiation capacity. However, tissue-derived MSCs (tMSCs) exhibit inconsistent characteristics. Although induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) are a potential solution, the effect of different embryonic lineages on their properties remains unknown. We generated MSCs from human iPSCs via five lineage-specific routes: cranial neural crest, trunk neural crest, paraxial mesoderm (somite), lateral plate mesoderm, and limb mesenchyme. All types met established MSC criteria yet differed in morphology, proliferation, and differentiation capacity. Somite-, cranial neural crest–, and limb mesenchyme–derived MSCs showed higher osteogenic potential, whereas somite-derived MSCs also showed high chondrogenic potential but were prone to hypertrophy. Limb mesenchyme–derived MSCs showed the highest adipogenic potential. Transcriptomic profiles indicated distinct clusters within iMSCs. Despite variances, a high correlation level existed between iMSCs and tMSC. Therefore, iMSCs are potential alternatives to tMSCs in regenerative medicine. Overall design: RNA-seq profiling was performed on five lineage-specific induced mesenchymal stem cell (iMSC) populations at passage 5 and their corresponding intermediate progenitors (cranial neural crest, trunk neural crest, somite, lateral plate mesoderm, and limb mesenchyme) expanded to passage 4, together with the parental iPSCs and tissue-derived MSCs derived from adipose tissue, bone marrow, dental pulp, and fibro/adipogenic progenitor (FAP) cells.