iPSC-derived cranial neural crest-like cells can replicate dental pulp tissue with the aid of angiogenic hydrogel

• Published in: Bioactive materials Vol. 14; pp. 290 - 301
• Main Authors: Kobayashi, Yoshifumi, Nouet, Julie, Baljinnyam, Erdenechimeg, Siddiqui, Zain, Fine, Daniel H., Fraidenraich, Diego, Kumar, Vivek A., Shimizu, Emi
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.08.2022; KeAi Publishing; KeAi Communications Co., Ltd
• Subjects: Angiogenic self-assembling peptide hydrogel; Cranial neural crest; Fibroblast growth factor; iPSC; Odontoblastic differentiation; Regenerative endodontics; Fibroblast growth factor; Odontoblastic differentiation; Regenerative endodontics; Cranial neural crest; iPSC; Angiogenic self-assembling peptide hydrogel
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2021.11.014

The dental pulp has irreplaceable roles in maintaining healthy teeth and its regeneration is a primary aim of regenerative endodontics. This study aimed to replicate the characteristics of dental pulp tissue by using cranial neural crest (CNC)-like cells (CNCLCs); these cells were generated by modifying several steps of a previously established method for deriving NC-like cells from induced pluripotent stem cells (iPSCs). CNC is the anterior region of the neural crest in vertebrate embryos, which contains the primordium of dental pulp cells or odontoblasts. The produced CNCLCs showed approximately 2.5–12,000-fold upregulations of major CNC marker genes. Furthermore, the CNCLCs exhibited remarkable odontoblastic differentiation ability, especially when treated with a combination of the fibroblast growth factors (FGFs) FGF4 and FGF9. The FGFs induced odontoblast marker genes by 1.7–5.0-fold, as compared to bone morphogenetic protein 4 (BMP4) treatment. In a mouse subcutaneous implant model, the CNCLCs briefly fated with FGF4 + FGF9 replicated dental pulp tissue characteristics, such as harboring odontoblast-like cells, a dentin-like layer, and vast neovascularization, induced by the angiogenic self-assembling peptide hydrogel (SAPH), SLan. SLan acts as a versatile biocompatible scaffold in the canal space. This study demonstrated a successful collaboration between regenerative medicine and SAPH technology. [Display omitted] •Cranial neural crest like cells (CNCLCs) were generated by simplifying a previously established method for deriving neural crest-like cells from iPSCs.•The produced CNCLCs showed approximately ∼12,000-fold upregulations of major CNC marker genes.•The combination of fibroblast growth factors, FGF4 and FGF9, induced the CNCLCs toward odontoblastic differentiation more effectively than BMP4.•In a mice subcutaneous implant model, the CNCLCs replicated the characteristics of dental pulp harboring vast neovascularization with the aid of the angiogenic hydrogel, SLan.