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.
Within the limitation of this study, the results indicate for the first time that fibrin-hOMSC constructs are endowed with the constitutive capacity to develop into mineralized tissues that exhibit certain similarities to cementum and bone.
Ischemic heart failure (IHF) is a leading cause for mortality and morbidity worldwide. Stem cell (SC) therapy is a promising strategy for IHF treatment. A major prerequisite for successful SC therapy is homogenous colonization of the infarcted myocardium. This process implies SC migration from the transplantation site. The purposes of the present study were to develop a new model system capable of quantifying SC migration within the infarcted myocardium and to assess the effect of post myocardial infarction (MI) remodeling on the migration of a newly identified neural crest SC population derived from the oral mucosa (hOMSC). MI was induced in rats. Myocardial scar tissue was collected at 0,1,3,7,14, and 28 days post-MI. DiI-labeledhOMSC were injected in the center of cylindrical scar tissue specimens harvested from each post-MI time point and transferred to organ culture. Changes in host and hOMSC cell densities were quantified in the center and periphery of specimens after 0, 3, 7, 14, and 28 days of culture by morphometric fluorescence microscopy. The results indicate a decrease in hOMSC density in the central zone and an increase in density in the peripheral zones indicating hOMSC migration from the central transplantation site to the rest of the infarcted myocardium. The average hOMSC density increased overtime due to cell proliferation. The level of hOMSC migration and proliferation was significantly affected by post-MI remodeling phase being higher in post-MI tissue that still comprised cardiomyofibers than in granulation and fibrotic tissues. Preliminary hOMSC transplantation in nude rat supports these findings. The present study shows that the new in vivo/in vitro model system is sufficiently sensitive to detect and quantify changes in the migratory capacity of stem cells within the infarcted myocardium and suggest that cell therapy applied in the early stages (up to 3 days) of post-MI remodeling facilitates the process of tissue colonization
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