Abstract: BACKGROUND: Mesenchymal stem cell transplantation is a promising new therapy for liver fibrosis, and the treatment effects are affected by many factors. The delivery route of mesenchymal stem cells is a key link in the treatment of liver fibrosis. There is controversy in the selection of the best transplantation route. The transplantation routes are particularly important to improve the treatment effects of mesenchymal stem cells.
OBJECTIVE: To investigate the treatment effects of mesenchymal stem cells in the treatment of liver fibrosis by different transplantation routes.
METHODS: Relevant articles from 2007 to 2021 in PubMed, CNKI, Wanfang and VIP databases were searched. The key words were “mesenchymal stem cells/stromal cells, liver/hepatic fibrosis/ cirrhosis, mechanism, distribution/biodistribution, transplantation route/delivery/engraftment/injection/administration” in Chinese and English, respectively. Repetitive, outdated and irrelevant views were excluded, and the 73 eligible articles were summarized and analyzed.
RESULTS AND CONCLUSION: (1) In the same conditions, the biodistributions of liver mesenchymal stem cells in different transplantation routes were different, and different anti-fibrotic mechanisms may play an important role in improving liver fibrosis in different niches, thus, exerting different treatment effects on fibrosis. (2) Animal experiments have shown that the effects of mesenchymal stem cell transplantation for treating liver fibrosis via intraportal vein are equivalent to that of intrahepatic artery and not inferior to that of intravenous vein, which is higher than intrahepatic and intraperitioneal effects. (3) Clinical studies have shown that intrahepatic and intrasplenic routes have similar treatment effects; intrahepatic artery and intraportal vein have the same effects and superior to the intravenous transplantation. (4) The routes via intrahepatic artery and intraportal vein may be the best way to treat liver fibrosis, and intrahepatic and intrasplenic routes may limit the therapeutic effects of stem cells because of “Cell crowding” and “Transient clearance”. (5) The transplantation routes of mesenchymal stem cells are safe and effective in the treatment of liver fibrosis. It may be beneficial to improve the treatment effects of mesenchymal stem cells to select appropriate approaches to increase stem cell colonization, enhance cell activity, and maintain the survival time of stem cells in liver tissue. It may be beneficial to improve the anti-fibrotic effect of mesenchymal stem cells, but the mechanisms of different transplantation routes are not so far clear, and the indications of different routes need to be further explored.

Key words: mesenchymal stem cell, liver fibrosis, liver cirrhosis, transplantation route, biodistribution, mechanism, treatment effect, tissue engineering