Published online Nov 7, 2019. doi: 10.3748/wjg.v25.i41.6190
Peer-review started: August 12, 2019
First decision: August 27, 2019
Revised: September 11, 2019
Accepted: October 17, 2019
Article in press: October 17, 2019
Published online: November 7, 2019
Processing time: 86 Days and 9.8 Hours
Acute liver failure (ALF) is a rapidly progressing liver disorder with extremely poor survival prognosis due to lack of effective treatment methods. In recent years, stem cell-based therapy has emerged as a new hope for revolutionizing the treatment of ALF. Thus, seeking for an ideal cell line for transplantation is of great importance.
Menstrual blood stem cells (MenSCs) are a group of easily accessible mesenchymal stem cells with advantages of a high level of immune privilege, robust replicative capacity and multipotential differentiation. However, little is known about the therapeutic effect of MenSCs in treating ALF in large animal models. MenSC transplantation could be a promising strategy for treating ALF.
The aim of this study was to investigate the efficacy of MenSCs for treating ALF in pigs and to dynamically trace the biodistribution of transplanted cells.
MenSCs were labelled in vitro with the fluorescent dye PKH26. Phenotypic analysis of MenSCs was performed using a flow cytometer. Cell viability was assessed by CCK-8. Cell multipotential differentiation was assessed by osteogentic and adipogenic differentiation. ALF porcine model was induced with D-galactosamine at a dose of 1.0 g/kg. The treatment group received transplantation of PKH26-labelled MenSCs via the portal vein under B-ultrasound guidance. The liver, lungs and spleen of sacrificed animals were imaged with the In vivo Imaging System (IVIS) using a CCD camera.
The labelling procedure did not affect the morphology, viability or multipotential differentiation of MenSCs. The survival time was significantly prolonged, and the levels of ALT, AST, TBIL and PT were obviously decreased in the treatment group compared with the control group. The liver pathological tissue in MenSC treatment group showed obviously increased numbers of remaining hepatocytes and a comparatively slight necrotic degree and area. The IVIS imaging revealed that PKH26-positive MenSCs were clearly retained in the liver initially and then diffused through the systemic circulation. The homing ability of MenSCs was confirmed by the markedly increased signal intensity in the liver at 36 h after transplantation. However, to achieve the optimal effectiveness of MenSC therapy, the therapeutic dose, cell preconditioning, the timing of cell grafting and the delivery route need to be further investigated.
This study showed that the immediate transplantation of MenSCs via the portal vein effectively improved liver function and coagulation, alleviated the progression of liver injury, and prolonged survival time. The study also demonstrated the ability of MenSCs to home to pathological hepatic environments after transplantation.
The therapeutic effect and homing ability of intraportally transplanted MenSCs in a porcine ALF model have been confirmed. MenSC transplantation may be a promising strategy for treating ALF.