RESUMEN
AIM: It is unknown if the beneficial effects of mesenchymal stromal cells (MSC) transplantation into the liver are dependent on their anchorage and differentiation into hepatocytes or rather the result of the release of stem cell intracellular content with hepatoprotector properties. MATERIALS & METHODS: The effects of intact MSC transplantation were compared with the infusion of MSC lysates in an experimental rat model of acute liver failure. RESULTS: A more powerful hepatoprotective and antiapoptotic effect was obtained after infusion of MSC lysates than intact MSC. Changes in IL-6 levels and miRNAs might explain the beneficial effects of MSC lysates. CONCLUSION: Infusion of MSC lysates show a better hepatoprotective effect than the transplantation of intact MSC.
Asunto(s)
Extractos Celulares/farmacología , Extractos Celulares/uso terapéutico , Hígado/fisiología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Citocinas/metabolismo , Femenino , Humanos , Inmunofenotipificación , Hígado/efectos de los fármacos , Hepatopatías/patología , Hepatopatías/terapia , MicroARNs/metabolismo , Células Madre Pluripotentes/citología , Vena Porta/fisiología , Ratas Wistar , Tioacetamida/administración & dosificación , Antígenos Thy-1/metabolismoRESUMEN
BACKGROUND: Cardiotrophin-1 (CT1) has been used to prevent cell death in different models of liver injury in rats. D-galactosamine induces cell death in culture rat and human hepatocytes. The present study evaluated the cytoprotective effects of CT1 in an experimental model of apoptosis induced by D-galactosamine in hepatocytes. METHODS: DNA fragmentation, calpain activity and Western blots of caspase-3, calpastatin and Stat3, and Akt phosphorylation were measured. Stat3 and Akt inhibitors were used to analyze the mechanisms of action of CT1. RESULTS: CT1 caused an increase in Stat3 and Akt phosphorylation and a decrease of DNA fragmentation, calpain activity, and caspase-3 induced by D-galactosamine. The reduction of calpain activity by CT1 was associated with an increase of calpastatin (its endogenous inhibitor). The effects of CT1 were also dependent on the activation of Sta3 or Akt. CONCLUSIONS: CT1 decreases cell death through a mechanism related to Stat3 and Akt phosphorylation and activation of calpastatin in D-galactosamine-treated hepatocytes.
