The Dynamic Tracing And Efficacy Of Menstrual Blood Stem Cells In Treating Acute Liver Failure

Background:In recent years,stem cell-based therapy has emerged to revolutionize the treatment of liver failure.Menstrual blood stem cells have been identified as a group of easily accessible mesenchymal stem cells with the advantages of non-invasive acquisition,low immunogenicity and their greater capacity of self renewal and multi-lineage differentiation,making them promising candidates for stem cell-based therapy.However,the potential mechanisms involved are not yet completely understood.Therefore,to optimize stem cell-based therapy,dynamic cell tracing and imaging is important for us to better understand the biological behaviors of stem cells after transplantation.Aim:To investigate the curative effect of menstrual blood stem cells in the treatment of Chinese miniature pigs with acute liver failure and to dynamically trace the biological distribution of PKH26 labeled stem cells after transplantation via portal vain.Method:Menstrual blood stem cells were labeled using PKH26 dye.PKH26 labeled menstrual blood stem cells were analyzed for their cytomorphology,viability and the adipogenic and osteogenic differentiation potential.Acute liver failure was induced in 36 male Bama miniature pigs weighting 8-12kg through intrajugular injection of D-galactosamine(l.Og/kg).The experimental animals were randomly divided into two groups:the treatment group received immediate intraportal transplantation of PKH labeled menstrual blood stem cells(2.5�106/kg)after D-galactosamine injection,and the control group received sham operation.The clinical features,liver fcunction,coagulation function,survival time and histological tissues were compared between the two groups.In addition,the livers,lungs and spleens were extracted from animals of the treatment group and imaged directly with the In vivo imaging system at different points in time.Result:The PKH26 labeling procedure did not impair the cytomorphology,viability,and the adipogenic and osteogenic differentiation potential.The survival time of the treatment group and the control group was 75.75�5.11 hours and 53.75�2.37 hours,respectively.Kaplan-Meier survival analysis showed that the treatment of menstrual blood stem cell therapy significantly prolonged the survival time of animals with acuteliver failure.The liver function deteriorated rapidly between 24 to 36 hours after induced acute liver failure.Menstrual blood stem cell therapy significantly reduced the prothrombin time,improved the liver function and alleviated hepatic inflammation and necrosis.In addition,the imaging results of In Vivo Imaging System revealed that most of the fluorescent signal retained in the liver.Total photon radiant efficiency of region of interest in the liver was 1.55�1010�2.97�108 p/s at 12 hours,decreased to 7.74�109�1.23�108 p/s at 24 hours,significantly increased to 3.65�1010�1.38�108 p/s and faded at 48 hours after stem cell engraftment.Conclusion:Menstrual blood stem cell therapy significantly improved the survival time of acute liver failure animals and our study demonstrated the capacity of stem cells to migrate to pathologic hepatic environments after engraftment.