Craniofacial Bone Regeneration using iPS Cell-Derived Neural Crest Like Cells

• Published in: Journal of Hard Tissue Biology Vol. 27; no. 1; pp. 1 - 10
• Main Authors: Kikuchi, Kazuko, Masuda, Tomoyuki, Fujiwara, Naoki, Kuji, Akiyoshi, Miura, Hiroyuki, Jung, Han-Sung, Harada, Hidemitsu, Otsu, Keishi
• Format: Journal Article
• Language: English; Japanese
• Published: Tokyo THE SOCIETY FOR HARD TISSUE REGENERATIVE BIOLOGY 01.01.2018; The Society for Hard Tissue Regenerative Biology; Japan Science and Technology Agency
• Subjects: Adipocytes; Biocompatibility; Biomarkers; Biomedical materials; Bone growth; Chondrocytes; Craniofacial bone regeneration; Dental pulp; Hydroxyapatite; Immunodeficiency; Induced pluripotent stem cells (iPSCs); Mesenchymal stem cells; Mesenchyme; Mice; Neural crest; Neural crest cells; Odontoblasts; Osteoblasts; Pluripotency; Regeneration; Regeneration (physiology); Stem cell transplantation; Stem cells; Surgical implants; Tissue engineering
• ISSN: 1341-7649; 1880-828X
• DOI: 10.2485/jhtb.27.1

Induced pluripotent stem (iPS) cells represent a powerful source for cell-based tissue regeneration because they are patient-specific cells and can differentiate into specialized cell types. Previously, we have demonstrated the derivation of neural crest like cells from iPS cells (iPS-NCLCs), and these cells have the potential to differentiate into dental mesenchymal cells, which subsequently differentiate into odontoblasts and dental pulp cells. In this study, we show that iPS-NCLCs can differentiate into mesenchymal stem cells (iPS-NCLC-MSCs), which contribute to craniofacial bone regeneration. iPS-NCLCs were cultured in serum-containing media and differentiated into functional MSCs, as confirmed by expression MSC markers and their ability to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro. iPS-NCLC-MSCs were negative for markers of undifferentiated iPS cells and did not develop into teratomas when transplanted to immunodeficient mice. Further, iPS-NCLC-MSCs grew normally and differentiated into osteoblasts on hydroxyapatite scaffolds in vitro. To assess the potential of iPS-NCLC-MSCs to regenerate craniofacial bone in vivo, iPS-NCLC-MSCs were transplanted into critical-size calvarial defects in immunodeficient mice for 8 weeks. Histological analysis revealed that iPS-NCLC-MSCs differentiated into osteoblasts and contributed to bone regeneration without tumor formation. These results indicate that iPS-NCLC-MSCs could be a potential candidate for cell-based craniofacial bone tissue repair and regeneration.