Nanocristais de TiO2 na fase rutilo-brookita aumentam a migração das células-tronco mesenquimais de tecido adiposo in vitro

Abstract

The regeneration of injured human body tissues has led to the development of innovative therapies. Among them, mesenchymal adipose-derived stem cells (MSC-ATs) and biocompatible TiO2 nanocrystals (NCs) have been considered promising therapeutic strategies for tissue engineering. TiO2 NCs have several crystalline forms that can affect the viability of MSC-ATs, and these combinations have not been previously investigated. To demonstrate the effects of TiO2 NCs on in vitro MSC-ATs, we evaluated different concentrations of Europium-doped Anatase-rutile (RA), rutile-anatase (RA) and rutile-brookite (RB) samples with respect to viability, cell migration and location of NCs in MSC-ATs. In vivo assays were also performed with the application of TiO2 - associated MSC-ATs in the rat maxillary region. Analyzes of the presence of metabolites in the MSC-ATs supernatant were performed after treatment with TiO2 NCs. The results showed that the NCs were not cytotoxic and remained in the cytoplasm without entering the nucleus, with significant increase in cell migration, presenting approximately 80% of lesion closure within 24 hours after treatment with 50ug / ml RB NCs. The in vivo analysis of fluorescence intensity generated by the presence of NCs was statistically higher in the maxilla when compared to control and treatment groups containing NCs with MSC-ATs supernatant. The maxilla and lung showed no histological changes with the application of TiO2 associated with MSC-ATs. In the chemometrics analysis of the supernatant of the stem cell culture treated with TiO2 NCs, phosphoenphingolipids subclass ceramide phosphoethanolamide metabolites, which are cell membrane structural lipids, important in cell signaling, cell growth regulation processes, were found. cell survival, immune system, vascular and epithelial integrity. Briefly, the association of TiO2 NCs with MSC-ATs was applied as a tissue regeneration strategy, evidenced by the increase of cell migration, without cytotoxicity effects and due to TiO2 NCs they remained in the cytoplasm without migrating to the nucleus. there are genotoxic effects.