Neural crest stem cell property of apical pulp cells derived from human developing tooth

Abstract

Recent reports have described that NCSCs (neural crest-derived stem cells) are not only present in the embryonic neural crest but also in the adult tissues. Dental pulp is one of mesenchymal soft tissues origin from cranial neural crest cells, and thought to be a source of adult stem cells. Here, we investigated the existence of NCSC-like cells in apical pulp of human developing tooth. Human impacted third molars with immature apex freshly extracted were obtained. The cells derived from the apical pulp tissue not framed by dentin or the coronal pulp tissues were cultured by primary explant culture. APDCs (apical pulp-derived cells) and CPCs (coronal pulp cells) formed spheres under neurosphere culture condition. The number of spheres from APDCs was larger than that from CPCs. The sphere-forming cells derived from APDCs had self-renewal capacity, and expressed neural crest-associated markers (p75, Snail and Slug) and NSC (neural stem cell) markers (Nestin and Musashi1). The expression pattern of mesenchymal stem cell markers, CD105 and CD166, on the surface of sphere-forming cells derived APDCs was different from that of APDCs. These sphere-forming cells could differentiate into multiple mesenchymal lineages (osteoblasts, adipocytes, chondrocytes and smooth muscle cells) and neural lineage (neurons) in vitro, and generated ectopic bone tissues on the border of HA (hydroxyapatite) scaffold in vivo. The results of this study suggest that APDCs contain cells with characteristics of NCSCs reported previously in mice. Humans developing tooth with immature apex is an effective source of cells for neural crest lineage tissue regeneration.

Stem Cells of Dental Origin: Current Research Trends and Key Milestones towards Clinical Application

“…has been also reported and linked to their embryonic origin [51, 52]. Sakai et al [53] have also shown that the majority of DPSCs and SHED expressed several neural lineage markers, including nestin, Doublecortin (DCX; neuronal progenitor cells), β III-tubulin (early neuronal cells), NeuN (mature neurons), GFAP (neural stem cells and astrocytes), S-100 (Schwann cells), A2B5, and CNPase (oligodendrocyte progenitor cells).…”

Neurogenic differentiation of human dental stem cellsin vitro

“…This means that the source of cells can influence the transplantation results, which reflect the origin of the adult stem cells sources9,10,11. Notably, dental stem cells can differentiate into neural crest-derived cells, such as neurons and glial cells, because they are obtained from tissue within the neural crest13,14,15. In some reports, dental stem cells show better neural stem cell properties than bone marrow-derived mesenchymal stem cells 16.…”

Nuclear Factor I-C (NFIC) Regulates Dentin Sialophosphoprotein (DSPP) and E-cadherin via Control of Krüppel-like Factor 4 (KLF4) During Dentinogenesis

“…6B). The Snail family members, Snail 1 and Slug, which encode zinc finger-type transcription factors, have been shown to be involved in neural crest formation and subsequent epithelial status (23,24). Consistent with microarray data, Slug expression was significantly increased in Nfic Ϫ/Ϫ pulp cells compared with wild type, whereas E-cadherin expression was decreased (Fig.…”