The Lamina Propria of the Oral Mucosa Harbors a Neural Crest-Like Stem Cell Population Resistant to Hyperglycemia Induced by Diabetes Type II
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Abstract
Oral mucosa stem cells (OMSC) are contained within niches in the lamina propria of the oral mucosa. In vitro, OMSC exhibit a primitive neural crest-stem cell phenotype and differentiate into neural crest-derived cell lineages. Clinical evidence indicate that wound healing of oral mucosa is scarless and negligibly affected by diabetes. Since stem cells play an important role in wound healing we hypothesized that in contrast to adult mesenchymal stem cells, OMSC are negligibly affected by diabetes type II hyperglycemia.
The capacity of murine OMSC (mOMSC) obtained from diabetic db+/db+ mice (DmOMSC) to proliferate, express pluripotency-associated markers (PAM) (oct4, sox2, nanog) and neural crest stem cell markers (NCSM) (Klf4, c-Myc, twist, nestin), and differentiate along neural crest cell lineages was compared to that of OMSC derived from background WT C57BL/6 mice (WT-mOMSC) and to those of murine adipose tissue stem cells (mASC) derived from the same animals used for generating mOMSC.
WT-mOMSC capacity to proliferate, express PAM and NCSM and differentiate was higher than that of WT-mASC. Diabetes reduced the proliferation rat of DmOMSC and db+/db+ derived mASC (DmASC) by 35% and 42%, respectively. Diabetes did not affect the expression of PAM and NSCSM in DmOMSC and nor their differentiation as compared to WT-mOMSC, but the diabetic state substantially reduced these parameters in DmASC as compared to WT-mASC and DmOMSC. We demonstrated that WT-mOMSC administration enhances wound healing in the db+/db+ diabetic wound skin model. To test the effect of diabetes on the therapeutic functionality of DmOMSC, the ability of these cells to enhance diabetic wound healing was assessed in this model. The results indicate that DmOMSC increased the rate of wound healing in db+/db+ mice as compared to placebo treated controls. The magnitude of this therapeutic effect is statistically equivalent to that of WT-mOMSC. Collectively, these data demonstrate that: i) diabetes decreased moderately DmOMSC proliferative ability; ii) in contrast to mASC, mOMSC withstand the detrimental effects of diabetes; and iii) the therapeutic properties of DmOMSC are mildly affected by long standing diabetes.
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