Increased Oral Fibroblast Lifespan Is Telomerase-independent

Abstract

Oral mucosal wound-healing is characterized by rapid re-epithelialization and remodeling, with minimal scar formation. This may be attributed to the distinct phenotypic characteristics of the resident fibroblasts. To test this hypothesis, we investigated patient-matched oral mucosal and skin fibroblasts. Compared with skin fibroblasts, oral mucosal fibroblasts had longer proliferative lifespans, underwent more population doublings, and experienced senescence later, which was directly related to longer telomere lengths within oral mucosal fibroblasts. The presence of these longer telomeres was independent of telomerase expression, since both oral oral mucosal fibroblasts and skin fibroblasts were negative for active telomerase, as assessed according to the Telomeric Repeat Amplification Protocol. This study has demonstrated that, compared with skin fibroblasts, oral mucosal fibroblasts are 'younger', with a more embryonic/fetal-like phenotype that may provide a notable advantage for their ability to repair wounds in a scarless fashion.

The Lamina Propria of Adult Human Oral Mucosa Harbors a Novel Stem Cell Population

“…Thus, their activity may explain the high-renewal capacity of hOMSC. Recently, Enoch et al [54] reported that OMLP-derived fibroblasts reach 80-115 population doublings before senescence, while donor matched skin fibroblasts only 40-65. This increased self-renewal capacity of OMLP-fibroblasts was telomerase-independent, but was related to increased telomeres length compared with skin fibroblasts suggesting that the OMPL population is endowed with inherent mechanisms that preserves telomere length.…”

Granulation tissue formation and remodeling

“…In contrast, several studies have shown that fibroblasts isolated from oral mucosa and skin have several inherent phenotypical differences, including a different capability for collagen remodeling, distinct secretion patterns for certain ECM molecules, different growth, migration and cell adhesion properties as well as differential expression of ECM receptors and response to growth factors. Consequently, the phenotype of oral mucosal fibroblasts exhibits similarities to fetal-type fibroblasts that contribute to scar-free healing in fetal skin (7,8,37,168,240,308,(310)(311)(312)(313)(314)(315)(316)(317)(318)(319)(320) (Table 4). These inherent differences may derive from a distinct embryonic developmental program between skin and oral mucosal fibroblasts as the former are derived from mesodermal mesenchymal cells and the latter from cells associated with the neural crest (325).…”

“…Oral mucosal wounds in rodents that heal faster than skin Results to scar formation Results to minimal scar formation TGF-b1/TGF-b3 isoform ratio higher TGF-b1/TGF-b3 isoform ratio lower Fundamental differences in the expression of MMPs, peptidases, cytokines and chemokines. 1 (7,8,37,168,240,247,273,274,308,(310)(311)(312)(313)(314)(315)(316)(317)(318)(319)(320)(321)(322)(323)(324).…”

Effects of a Nonthermal Atmospheric Pressure Plasma Jet on Human Gingival Fibroblasts for Biomedical Application

“…The study was undertaken using human normal gingival fibroblasts (hNOF) in situ in order to evaluate biocompatibility of titanium dental implant in contact with the mucosal gingival [16]. However, such hNOF cannot be consistently used for evaluating cytotoxicity of dental products, due to the limited lifespan in serial culture and the genomic instability in later passages [17, 18]. It was studied that the cytotoxicity response of hTERT-hNOF cells is significantly similar to human normal gingival fibroblasts (hNOF) and more sensitive compared to L929 cells with genomic stability even at the later passages [19].…”