Hyaluronic Acid Induction Promotes the Differentiation of Human Neural Crest-like Cells into Periodontal Ligament Stem-like Cells

• Published in: Cells (Basel, Switzerland) Vol. 12; no. 23; p. 2743
• Main Authors: Alhasan, M Anas, Tomokiyo, Atsushi, Hamano, Sayuri, Sugii, Hideki, Ono, Taiga, Ipposhi, Keita, Yamashita, Kozue, Mardini, Bara, Minowa, Fumiko, Maeda, Hidefumi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.11.2023
• Subjects: Analysis; Care and treatment; CD44 antigen; Cell differentiation; Cementum; Diagnosis; Dosage and administration; electrospun nanofibrous membranes; Extracellular matrix; Gene expression; Gum disease; Hyaluronic acid; hyaluronic acid-CD44 signalling; Ligaments; Nervous system; Neural crest; neural crest cells; Neuroblastoma; Periodontal disease; Periodontal ligament; Periodontium; Pluripotency; Reagents; Regeneration; Stem cells; Tissue engineering; Transplantation; Japan; St Louis Missouri; Grand Island; United States > US; hyaluronic acid-CD44 signalling; stem cells; periodontal ligament; neural crest cells; electrospun nanofibrous membranes
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12232743

Periodontal ligament (PDL) stem-like cells (PDLSCs) are promising for regeneration of the periodontium because they demonstrate multipotency, high proliferative capacity, and the potential to regenerate bone, cementum, and PDL tissue. However, the transplantation of autologous PDLSCs is restricted by limited availability. Since PDLSCs are derived from neural crest cells (NCs) and NCs persist in adult PDL tissue, we devised to promote the regeneration of the periodontium by activating NCs to differentiate into PDLSCs. SK-N-SH cells, a neuroblastoma cell line that reportedly has NC-like features, seeded on the extracellular matrix of PDL cells for 2 weeks, resulted in the significant upregulation of PDL marker expression. SK-N-SH cell-derived PDLSCs (SK-PDLSCs) presented phenotypic characteristics comparable to induced pluripotent stem cell (iPSC)-derived PDLSCs (iPDLSCs). The expression levels of various hyaluronic acid (HA)-related genes were upregulated in iPDLSCs and SK-PDLSCs compared with iPSC-derived NCs and SK-N-SH cells, respectively. The knockdown of in SK-N-SH cells significantly inhibited their ability to differentiate into SK-PDLSCs, while low-molecular HA (LMWHA) induction enhanced SK-PDLSC differentiation. Our findings suggest that SK-N-SH cells could be applied as a new model to induce the differentiation of NCs into PDLSCs and that the LMWHA-CD44 relationship is important for the differentiation of NCs into PDLSCs.