Effect of mesenchymal stem cell conditioned medium on hepatocyte matrix implant to alleviate liver cirrhosis in rats.

Background
Hepatocyte transplantation has gained importance as an alternative treatment to orthotopic liver transplantation for end-stage liver disease. This study explores the modification of the hepatocyte matrix implant (HMI) procedure by replacing islet cells with conditioned medium (CM) derived from human umbilical cord-MSC (hUC-MSC) supplementation to alleviate liver cirrhosis in a rat model.
Methods
The male Sprague Dawley rats were induced liver cirrhosis using thioacetamide for 11 weeks, and implanted with matrices on the small bowel mesentery, according to the groups. Four groups were assessed: blank matrix (cell-free), hepatocytes seeded-matrix (Hep), hepatocytes+islets co-seeded-matrix (Hep:Islet), and hepatocytes seeded-matrix supplemented with CM (Hep+CM).
Results
In vitro, the Hep+CM group showed significantly higher hepatocyte proliferation than the Hep:Islet group, though albumin production was similar. The in vivo study further confirmed that the implanted hepatocytes remained viable and were able to produce albumin for at least 4 months post-implantation. Liver function parameters were shown to be improved in Hep:Islet and Hep+CM groups. Notably, collagen deposition in the liver was lower in Hep:Islet and Hep+CM groups compared to other groups.
Conclusion
These findings suggest that CM can effectively replace islet in supporting hepatocyte proliferation and function, enhancing the therapeutic potential of HMI procedure. No writing assistance was utilized in the production of this manuscript or liver cirrhosis treatment.Liver cirrhosis is a severe liver disease that often leads to life-threatening complications, with the only curative option for advance cirrhosis cases is through liver transplantation. However, due to the shortage of donor organs, alternative therapies are urgently needed. In our previous study, we developed a method called hepatocytes matrix implant. In this approach, liver cells were placed together with pancreatic cells on a polymer scaffold as cell carrier, and implanted into the small bowel mesentery to temporarily support liver function as a bridging therapy. In the present study, we explored a modified approach by replacing the pancreatic cells with conditioned medium derived from mesenchymal stem cells (CM MSC, which are known to exert regenerative properties. Through this innovation, additional pancreatic resection is no longer needed, preventing the risks of complication. Our findings show that liver cells stimulated with CM MSC showed equal or even better results compared to those stimulated by pancreatic cells. In animal studies, these implanted cells survived for several months, improving liver function. These findings suggest that CM-MSC could become a simpler and more promising alternative to pancreatic cells in supporting hepatocytes transplantation, potentially offering a new therapeutic option for liver cirrhosis patients.