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

Abstract

The highly regenerative capacity of the human adult oral mucosa suggests the existence of a robust stem cell (SC) population in its lamina propria (OMLP). The purpose of this study was to characterize the availability, growth, immunophenotype, and potency of this presumable SC population. Cells positive for the embryonic stem cell transcription factors Oct4 and Sox2 and for p75 formed distinct cord-like structure in the OMLP. Regardless of donor age, trillions of cells, termed human oral mucosa stem cells (hOMSC), 95% of which express mesenchymal stromal cell markers, were simply, and reproducibly produced from a biopsy of 3-4 3 2 3 1 mm 3 . A total of 40-60% of these cells was positive for Oct4, Sox2, and Nanog and 60-80% expressed constitutively neural and neural crest SC markers. hOMSC differentiated in culture into mesodermal (osteoblastic, chondroblastic, and adipocytic), definitive endoderm and ectodermal (neuronal) lineages. Unexpectedly, hOMSC treated with dexamethasone formed tumors consisting of two germ layer-derived tissues when transplanted in severe combined immune deficiency mice. The tumors consisted of tissues produced by neural crest cells during embryogenesis-cartilage, bone, fat, striated muscle, and neural tissue. These results show that the adult OMLP harbors a primitive SC population with a distinct primitive neural-crest like phenotype and identifies the in vivo localization of putative ancestors for this population. This is the first report on ectodermal-and mesodermal-derived mixed tumors formation by a SC population derived from a nonmalignant somatic adult human tissue. STEM CELLS 2010;28:984-995 Disclosure of potential conflicts of interest is found at the end of this article.

Human exfoliated deciduous teeth and oral mucosa: promising applications in tissue regeneration

“…The demonstrated great potential of SHEDs and OMSCs 16,17,[24][25][26] and the relatively easy collecting and harvesting method, led us to suggest the opportunity to use the deciduous teeth, naturally lost in pediatric age, and/or the oral mucosa, for TR purposes of patients.…”

“…the lamina propria) another promising source of stem cells; the population of SCs was heterogeneous: part of it expressed embryonic stem cell transcription factors as Oct4, SOX2 and SSEA-4 part of it expressed the canonical MSC markers as CD29, CD73, CD90, CD105, CD166 and Stro1. They were able to differentiate towards mesodermal and ectodermal lineages 25 .…”

Periodontal Stem Cells: a Historical Background and Current Perspectives

“…(3) Are the quiescent and active populations endowed with same potency (stemness)? (4) What are the cells that migrate into the periodontal ligament from endosteal spaces of the alveolar bone and what is their role? (5) What are the molecular cues that direct their migration?…”

Myogenic potential of human alveolar mucosa derived cells

“…24,25 Namely, they have strong immunomodulatory properties, 25 ability to differentiate into neuronal direction due to its development from neural crest. 26,27 Moreover, the amount of MMSC able to multipotent differentiation is higher in gingival mucosa compared to other tissues. 28,29,30 In primary cultures of gingival fibroblasts up to 90% of cells possess "stemness" markers and 40-70% of cells express pluripotency genes such as Oct4, Sox2, Nanog 28 and active telomerase.…”