Derivation and characterization of putative craniofacial mesenchymal progenitor cells from human induced pluripotent stem cells

The introduction and widespread adoption of induced pluripotent stem cell (iPSC) technology has opened new avenues for craniofacial regenerative medicine. Neural crest cells (NCCs) are the precursor population to many craniofacial structures, including dental and periodontal structures, and iPSC-derived NCCs may, in the near future, offer an unlimited supply of patient-specific cells for craniofacial repair interventions. Here, we used an established protocol involving simultaneous Wnt signaling activation and TGF-β signaling inhibition to differentiate three human iPSC lines to cranial NCCs. We then derived a mesenchymal progenitor cell (NCC-MPCs) population with chondrogenic and osteogenic potential from cranial NCCs and investigated their similarity to widely studied human postnatal dental or periodontal stem/progenitor cells. NCC-MPCs were quite distinct from both their precursor cells (NCCs) and bone-marrow mesenchymal stromal cells, a stromal population of mesodermal origin. Despite their similarity with dental stem/progenitor cells, NCC-MPCs were clearly differentiated by a core set of 43 genes, including ACKR3 (CXCR7), whose expression (both at transcript and protein level) appear to be specific to NCC-MPCs. Altogether, our data demonstrate the feasibility of craniofacial mesenchymal progenitor derivation from human iPSCs through a neural crest-intermediate and set the foundation for future studies regarding their full differentiation repertoire and their in vivo existence.