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 significant and complex hepatic insult that may rapidly progress to life-threatening conditions. Recently, menstrual blood stem cells (MenSCs) have been identified as a group of easily accessible mesenchymal stem cells with the advantages of non-invasive acquisition, low immunogenicity, a greater capacity of self-renewal and multi-lineage differentiation, making them promising candidates for stem cell-based therapy to revolutionize the treatment strategies for liver failure.
To investigate the therapeutic potential of MenSCs for treating ALF in pigs and to dynamically trace the biodistribution of transplanted cells.
MenSCs were labeled in vitro with PKH26, a lipophilic fluorescent dye. The treatment group received immediate transplantation of PKH26-labelled MenSCs (2.5 × 106/kg) via the portal vein after D-galactosamine injection, and the control group underwent sham operation. The survival time, liver function, and hepatic pathological changes were compared between the two groups. Three major organs (liver, lungs and spleen) were extracted from animals and imaged directly with the In vivo Imaging System (IVIS) at the predetermined time points. The regions of interest were drawn to quantify the cell uptake in different organs.
The labelling procedure did not affect the morphology, viability or multipotential differentiation of MenSCs. Biochemical analysis showed that the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and prothrombin time (PT) measured at selected time points 24 h after transplantation were significantly decreased in the treatment group (P < 0.05). The survival time of ALF animals was prolonged in the treatment group compared with the control group (75.75 ± 5.11 h vs 53.75 ± 2.37 h, log rank, P < 0.001). The liver pathological tissue in the MenSC treatment group showed obviously increased numbers of remaining hepatocytes and a comparatively slight necrotic degree and area. In addition, the IVIS imaging revealed that PKH26-positive MenSCs were clearly retained in the liver initially and then diffused through the systemic circulation. Interestingly, the signal intensity in the liver increased obviously at 36 h, which corresponded to the biochemical result that liver function deteriorated most rapidly at 24 - 36 h.
Our study demonstrates the therapeutic efficacy and homing ability of transplanted MenSCs in a large animal model of ALF and suggests that MenSC transplantation could be a promising strategy for treating ALF.
Core tip: In this study, we investigated for the first time the therapeutic potential of intraportally transplanted menstrual blood stem cells (MenSCs) in treating pigs with acute liver failure, and showed that MenSC treatment improved liver function and coagulation, alleviated the progression of liver injury, and prolonged the survival time of pigs. Additionally, ex vivo imaging also demonstrated the ability of MenSCs to home to pathological hepatic environments after transplantation. MenSC transplantation has the potential to be used as an available source for treating acute liver failure in future clinical therapy.