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

Abstract

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 diff erentiate into dental mesenchymal cells, which subsequently diff erentiate into odontoblasts and dental pulp cells. In this study, we show that iPS-NCLCs can diff erentiate into mesenchymal stem cells (iPS-NCLC-MSCs), which contribute to craniofacial bone regeneration. iPS-NCLCs were cultured in serum-containing media and diff erentiated into functional MSCs, as confi rmed by expression MSC markers and their ability to diff erentiate into osteoblasts, adipocytes, and chondrocytes in vitro. iPS-NCLC-MSCs were negative for markers of undiff erentiated iPS cells and did not develop into teratomas when transplanted to immunodefi cient mice. Further, iPS-NCLC-MSCs grew normally and diff erentiated into osteoblasts on hydroxyapatite scaff olds 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 immunodefi cient mice for 8 weeks. Histological analysis revealed that iPS-NCLC-MSCs diff erentiated 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.

Neural crest-like stem cells for tissue regeneration

“…In comparison to human BM‐MSCs, tissue engineered constructs of MSCs from iPSC‐derived NCLSCs did not undergo chondrogenesis in vivo nor did they effectively repair osteochondral defects 158 . On the other hand, mouse iPSC‐NCLSC‐MSCs transplanted into calvarial defects differentiated into osteoblasts, produced no tumors, and contributed to bone regeneration 159 . These studies highlight how these derived cells may behave differently in vivo.…”

“…PSC‐derived NCLSCs have also been differentiated into various cell types, including MSCs, osteocytes, and chondrocytes, that are beneficial for bone, cartilage, and tendon regeneration 30,156‐160 . Xu et al examined whether iPSC‐derived NCLSCs could repair a rat patellar tendon window defect.…”

Dental applications of induced pluripotent stem cells and their derivatives

“…Anti-BMP2 antibody/BMP2 immune complex induces iMSCs to acquire osteogenic phenotype and mineralization, which suggests that antibody-induced osteogenic differentiation could be an alternative technology for iPSC-based tissue regeneration [115] . Kikuchi et al recently differentiated iNCCs into iMSCs, which were differentiated into osteoblasts, adipocytes, and chondrocytes in vitro, and had capability to regenerate craniofacial bone in vivo without tumor formation [116] .…”

Tissue Engineering and Regenerative Medicine: Achievements, Future, and Sustainability in Asia

“…Yanaga et al (2006) made an attempt to use a composite of autologous human auricular chondrocytes with autologous serum for craniofacial augmentation in a pilot clinical study. Otsu's group revealed that neural crest-like cells from iPS cells could differentiate into osteoblasts and contribute to craniofacial bone regeneration without tumor formation in vivo (Kikuchi et al, 2018). This method could resolve the limitation of insufficient source of reconstructive material.…”