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

Abstract

Abstract:‎ 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.‎