Potencial terapêutico de células-tronco mesenquimais diretamente reprogramadas em hepatócitos, em modelo experimental de insuficiência hepática aguda

Abstract

Introduction: The high prevalence of hepatopathies in the general population has led to the constant search for new therapeutic alternatives, aimed at the treatment and / or cure of such diseases. Currently, the use of cell therapy from mesenchymal stem cells has been growing more and more as a viable alternative. Since one can use cells of the own carrier of the disease, bypassing problems like rejection by the immune system. However, several problems still need to be overcome: acquisition of large numbers of viable cells for use in cell therapy and a greater adhesion of these cells to the injured organ. The present study aims to establish the effectiveness of cell therapy promoted by hepatocytes derived from mesenchymal stem cells (iHeps) as a therapeutic alternative in an experimental model of acute hepatic failure induced by acetoaminophen in C57B1 / 6 mice. Method: C57B1 / 6 mice were used for three weeks using 10% ethanol ad libitum instead of water. Subsequently, 450 mg / kg of acetoaminophen, diluted in saline intraperitoneally, was injected for induction of acute liver injury. Four hours after administration of acetoaminophen, iHEPs (2,106 cells / mouse) were transplanted intrahepatically. Immunofluorescence was used for cell screening and proliferation verification in the hepatic parenchyma (48 hours and 2 weeks after transplantation). Survival analysis was performed for seven days. Results: The mortality curve proposed in the model was established with 10% ethanol for 3 weeks and injection of 450mg / kg of acetoaminophen; by immunofluorescence it was possible to demonstrate transdifferentiated hepatocytes adhered and proliferating in the hepatic parenchyma. Survival analysis did not show a statistically significant difference in mortality in the Kaplan-meier model for survival. Conclusion: The cells demonstrated the capacity of grafting and proliferation in the model of acetoamphrine acute liver failure. It was not possible to establish an impact on the survival of these mice in this experimental model.