TY - JOUR
T1 - iPSC-derived cranial neural crest-like cells can replicate dental pulp tissue with the aid of angiogenic hydrogel
AU - Kobayashi, Yoshifumi
AU - Nouet, Julie
AU - Baljinnyam, Erdenechimeg
AU - Siddiqui, Zain
AU - Fine, Daniel H.
AU - Fraidenraich, Diego
AU - Kumar, Vivek A.
AU - Shimizu, Emi
N1 - Funding Information: This study was supported by NIH grants, R01DE025885 (E.S), R15EY029504 (VAK), and National Science Foundation NSF IIP 1903617 (VAK). Publisher Copyright: © 2021 The Authors
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
KW - Angiogenic self-assembling peptide hydrogel
KW - Cranial neural crest
KW - Fibroblast growth factor
KW - Odontoblastic differentiation
KW - Regenerative endodontics
KW - iPSC
UR - http://www.scopus.com/inward/record.url?scp=85119933588&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85119933588&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.bioactmat.2021.11.014
DO - https://doi.org/10.1016/j.bioactmat.2021.11.014
M3 - Article
SN - 2452-199X
VL - 14
SP - 290
EP - 301
JO - Bioactive Materials
JF - Bioactive Materials
ER -