Abstract
The aim of the present study is to evaluate the potential differentiation ability of gingiva originated human mesenchymal stem cell in the presence of tacrolimus. Tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres were prepared using electrospraying technique. In vitro release study of tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres was performed in phosphate-buffered saline (pH 7.4). Gingiva-derived stem cells were isolated and incubated with tacrolimus or tacrolimus-loaded microspheres. Release study of the microspheres revealed prolonged release profiles of tacrolimus without any significant initial burst release. The microsphere itself did not affect the morphology of the mesenchymal stem cells, and cell morphology was retained after incubation with microspheres loaded with tacrolimus at 1 μg/mL to 10 μg/mL. Cultures grown in the presence of microspheres loaded with tacrolimus at 1 μg/mL showed the highest mineralization. Alkaline phosphatase activity increased with an increase in incubation time. The highest expression of pSmad1/5 was achieved in the group receiving tacrolimus 0.1 μg/mL every third day, and the highest expression of osteocalcin was achieved in the group receiving 1 μg/mL every third day. Biodegradable poly(lactic-co-glycolic acid)-based microspheres loaded with tacrolimus promoted mineralization. Microspheres loaded with tacrolimus may be applied for increased osteoblastic differentiation.
Highlights
IntroductionBiodegradable poly(lactic-co-glycolic acid)-based microspheres loaded with tacrolimus promoted mineralization
The aim of the present study is to evaluate the potential differentiation ability of gingiva originated human mesenchymal stem cell in the presence of tacrolimus
Our previous report showed that tacrolimus in concentrations ranging from 0.001 to 10 μg/mL did not produce statistically significant differences in the viability of stem cells derived from gingiva, but rather enhanced the osteogenic differentiation of the stem cells[4]
Summary
Biodegradable poly(lactic-co-glycolic acid)-based microspheres loaded with tacrolimus promoted mineralization. Biodegradable microspheres were applied for the sustained delivery of drugs for the enhancement of the differentiation ability human mesenchymal stem cells. The osteogenic differentiation of bone marrow-derived mesenchymal stem cells is greatly promoted by the application of tacrolimus[7]. Our previous report showed that tacrolimus in concentrations ranging from 0.001 to 10 μg/mL did not produce statistically significant differences in the viability of stem cells derived from gingiva, but rather enhanced the osteogenic differentiation of the stem cells[4]. A previous report showed that tacrolimus-loaded biodegradable microspheres achieved sustained release over a long period, yielding flat parallel concentration profiles for 10 days from the first day after a single subcutaneous administration in liver-transplanted rats[9].
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