Dental Follicle Progenitor Cell Heterogeneity in the Developing Mouse Periodontium

Abstract

As a developmental precursor for diverse periodontal tissues, the dental follicle (DF) harbors great promise for periodontal tissue regeneration. However, development of optimal therapy awaits the answer to a key question that impinges on many issues in development-Do adult progenitor tissues form a homogeneous cell population that differentiates into target tissues when they arrive at the site, or they contain heterogeneous cell populations that are committed to specific fates? To address the homogeneity/heterogeneity question, we analyzed differentiation pathways and markers in several cloned DF cell lines. Our studies revealed that each of our cloned DF lines featured remarkably unique characteristics, indicative of a separate and distinct lineage. One line, DF1, was high in proliferative activity but did not display any mineralization behavior, suggesting that it might be related to a periodontal ligament-type lineage. DF2 was similar to DF1, but featured remarkably high alkaline phosphatase activity indicative of a highly undifferentiated state. DF3 matched the mineralization characteristics of a same stage alveolar bone line AB1 in terms of gene expression and von Kossa staining, indicating that DF3 might be of cementoblastic or alveolar bone osteoblastic lineage. To verify the multilineage potential of the DF for purposes of tissue engineering, a series of differentiation induction experiments was conducted. For identification purposes, characteristics of these heterogeneous follicular progenitor cells were compared with follicle components in tissue sections of the postnatal developing periodontium. The presence of heterogeneous cell populations in the DF mirrors individual developmental pathways in the formation of the dental integument. The profound cellular heterogeneity of the DF as an adult progenitor for tissue regeneration also suggests that heterogeneous cellular constituents might play as much of a role in tissue regeneration as the inducible characteristics of individual lineages might do.

Tooth-derived stem cells: Update and perspectives

“…The dental follicle is a condensation of ectomesenchymal cells that surrounds the tooth germ in early stages of tooth formation and contains cells that form the three tissues that constitute the periodontium: periodontal ligament, cementum and alveolar bone [54,72] . When the it was supposed that putative MSCs would be present in the periodontal ligament, which was confirmed in 2004 [73] .…”

“…Moreover, it was observed that, although DePDL and PDSLCs have the ability to differentiate into both adipocyte-like and osteoblastlike cells in vitro, DePDL show a higher potential for adipogenic commitment, and PDLSCs have a higher potential for osteogenic commitment [60] . heterogeneity of DPFCs was analyzed, it was observed that, although all cloned cell lines were positive for MSCrelated surface markers (CD105, CD44, CD29) and negative for hematopoietic markers (CD34, CD117), they were different in terms of proliferation and mineralization patterns, indicating that they could be committed to distinct lineages [72] . In order to avoid donor variability, TDSCs from follicle, pulp and papilla were isolated from a single donor tooth and the morphology, proliferation rate, expression of MSC-specific and pluripotency markers, and in vitro differentiation into osteoblasts, adipocytes, chondrocytes and hepatocyte-like cells were compared [65] .…”

Periodontal Ligament Stem Cells

“…As a consequence, clonal PDL cell lines derived from mice (Saito et al, 2002), swine (Ibi et al, 2007) and humans (Kamata et al, 2004;Fujita et al, 2005;Pi et al, 2007;Mi et al, 2011) have been developed. In addition, clonal cell lines from mouse dental follicle (DF) cells as a source of PDLSCs have also been reported (Saito et al, 2005;Luan et al, 2006). However, the multipotency in these cell lines has not been analyzed in detail.…”

Histopathological and Immunohistochemical Study of the Characteristics of Dental Follicle

“…In recent years, progenitor cells have been identified in the DF 2,3) , demonstrated to differentiate along osteogenic pathways 4,5) . Additionally, the DF attached to impacted tooth has been used to analyze the differentiation into various cell types including cementoblasts, adipocytes, chondrocytes, fibroblasts or osteoblasts.…”