A Multipotent Neural Crest-Derived Progenitor Cell Population Is Resident Within the Oral Mucosa Lamina Propria

Abstract

Wounds within the oral mucosa, similarly to fetal wounds, exhibit rapid healing with reduced scarring. We hypothesized that a progenitor population resident within the oral mucosal lamina propria (OMLP) contributes to this preferential healing. Progenitor cells (PC) were reliably isolated from the OMLP by differential adhesion to fibronectin. Isolated colonies originating from a single cell demonstrated a rapid initial phase of proliferation, completing in excess of 50 population doublings (PDs) before entering cellular senescence. These data were supported by the expression of active telomerase within both developing colonies and expanded clones as assessed by immunocytochemistry (ICC) and the quantitative telomeric repeat amplification protocol. FACS analysis confirmed expression of the stem cell markers CD44, CD90, CD105, and CD166, but negative expression of CD34 and CD45 ruling out a hematopoietic or fibrocyte origin for these progenitors. A neural crest origin was confirmed by increased colony-forming efficiency (CFE) in the presence of Jagged 1 and the expression of a number of neural crest markers within the developing colonies by ICC and serially passaged clones by Western blotting. The multipotency of this novel PC population was demonstrated by differentiation of the cells down both mesenchymal (chondrogenic, osteoblastic, and adipogenic) and neuronal (neuron and Schwann-like cells) cell lineages. This article reports for the first time, the isolation and characterization of a novel, clonally derived PC population resident within the OMLP. The attributes of this adult stem cell (ASC) population and its accessibility lends itself to future therapeutic applications.

Functional Effects of Adult Human Olfactory Stem Cells on Early-Onset Sensorineural Hearing Loss

“…Together, these results provide evidence of a beneficial effect of olfactory stem cell transplantation on hearing levels in A/J mice. Recent studies of adult olfactory and oral mucosae reveal that the lamina propria within these tissues are a source of mesenchymal stem cells with extensive differentiation potential [24,[36][37][38]. The olfactory mucosa also contains neural stem cells, situated within the olfactory epithelium, maintaining a lifelong turnover of olfactory receptor neurons [39].…”

Human Oral Mucosa and Gingiva

“…In addition to these tri-lineage potentials, oral mucosa-/gingiva-derived MSCs are capable of differentiating into endodermal and ectodermal lineages, including various types of neural cells (Zhang et al, 2009;Davies et al, 2010;Marynka-Kalmani et al, 2010). As found in vivo, oral mucosa-/gingiva-derived MSCs embedded with carriers and subcutaneously transplanted into immunocompromised mice can generate connective tissue-like structures (Zhang et al, 2009;Tang et al, 2011), bone matrix (Fournier et al, 2010;Wang et al, 2011) and even 2 germ-layer-derived (teratoma-like) tissues (Marynka-Kalmani et al, 2010).…”

“…Importantly, human oral mucosa-and gingiva-derived MSCs invariably display a higher proliferation rate than do BMSCs (Zhang et al, 2009;Davies et al, 2010;Marynka-Kalmani et al, 2010;Tomar et al, 2010;Tang et al, 2011), which was likely attributed to the constitutive expression of human reverse telomerase transcriptase (hTERT) (Zhang et al, 2009;Davies et al, 2010). Moreover, the in vivo self-renewal capacity of gingiva-derived MSCs has been demonstrated by serial subcutaneous (s.c.) transplantation in immunocompromised mice (Zhang et al, 2009;Tang et al, 2011).…”

Integration-Free Reprogramming of Lamina Propria Progenitor Cells

“…OMLP-PCs were then isolated by differential adhesion to fibronectin as previously described (Davies et al 2010). H9 human embryonic stem cell (hESC) lines from WiCell were utilized as positive control and cultured as previously described (Thomson et al 1998).…”

“…The oral mucosal lamina propria (OMLP) harbors a population of multipotent and potently immunosuppressive progenitor cells (PCs; Davies et al 2010;Davies et al 2012). Given the well-reported scarless wound-healing ability of the oral mucosa, OMLP-PCs represent a readily accessible cell source with favorable growth kinetics and potential utility for a variety of personalized regenerative medicine applications.…”