# Luopan Mountain Pig Bone Marrow Mesenchymal Stem Cells Promote Liver Regeneration in D-Galactosamine-Induced Acute Liver Failure Rats by Regulating the PTEN-PI3K/Akt/mTOR Pathway

## TL;DR

Pig stem cells from Luopan Mountain pigs help repair liver damage in rats with acute liver failure by activating a key repair pathway.

## Contribution

This is the first study to show Luopan Mountain pig stem cells promote liver regeneration via the PTEN-PI3K/Akt/mTOR pathway in a rat model.

## Key findings

- pBMSCs improved survival and reduced liver damage in rats with acute liver failure.
- The treatment activated the PI3K/Akt/mTOR pathway and suppressed PTEN, aiding liver regeneration.
- pBMSCs reduced hepatocyte apoptosis and enhanced liver function markers like HGF and IGF-1.

## Abstract

Acute liver failure is a serious condition in which the liver stops working. Treatment options for this condition are limited, as there are not enough donor organs for transplants and the body often rejects transplanted organs. In this study, we investigated a potential new treatment using stem cells from a special breed of pig. We aimed to assess whether these cells could help to repair the damaged liver in rats with induced liver failure. Our results showed that injecting these pig stem cells into the rats greatly improved their survival. The treatment helped the liver to heal by reducing tissue damage, improving function, and encouraging the organ to regenerate. We also discovered that the cells work by activating a specific repair pathway in the liver. This research is a first step toward a new treatment for liver failure that could help to save human lives by providing an alternative to scarce human organ transplants in the future.

Treatment for acute liver failure (ALF) is constrained by shortages of liver transplant donors and immune rejection. Porcine bone marrow mesenchymal stem cells (pBMSCs) demonstrate clinical potential in xenotransplantation due to their abundant availability, low immunogenicity, and strong proliferative activity. This study is the first to investigate the reparative effects and mechanisms of pBMSCs derived from Luopan Mountain pigs in a D-galactosamine (D-GalN)-induced ALF rat model. The results demonstrated that tail-vein transplantation of pBMSCs significantly improved survival rates in ALF rats; reduced serum ALT, AST, and TBIL levels; enhanced hepatic glycogen metabolism; and mitigated histopathological liver damage. Additionally, pBMSC transplantation upregulated serum HGF, IGF-1, and VEGF levels while inhibiting hepatocyte apoptosis. Mechanistic studies indicate that pBMSCs promote liver function recovery and regeneration by activating the PI3K/Akt/mTOR signaling pathway and suppressing its key negative regulator, PTEN, by regulating the expression of key genes involved in inflammation, fibrosis, proliferation, and apoptosis. This study provides crucial experimental evidence for the use of pBMSCs in treating acute liver failure (ALF) and lays the groundwork for its clinical translation in the field of xenotransplantation.