Transplantation with GXHPC1 for Liver Cirrhosis: Phase 1 Trial

Abstract

Currently, the only effective therapy for cirrhosis of the liver is liver transplantation. However, finding a compatible liver is difficult due to the low supply of healthy livers and the ever-increasing demand. However, stem-cell therapy may offer a solution for liver cirrhosis; for example, GXHPC1 therapy preparation contains adipose-derived mesenchymal stem cells (AD-MSCs) and was developed for the treatment of liver cirrhosis. In our previous report, animal studies suggested that treatment of a diseased liver via GXHPC1 transplantation can abrogate liver fibrosis and facilitate recovery of liver function. In our current human trial, patients with liver cirrhosis were included. Their adipose tissue was harvested from the subcutaneous fat of the abdominal wall during surgery. AD-MSCs were cultured and suspended at a concentration of 100 million cells in 1 ml of physiological saline (i.e., GXHPC1). This human study passed the Taiwan Food and Drug Administration IND inspection and received Phase I clinical trial permission. The trial was conducted with six patients with liver cirrhosis to demonstrate the safety and efficacy of administering GXHPC1. Intrahepatic injection of GXHPC1 did not cause any safety issues in the analysis of adverse drug reactions and suspected unexpected serious adverse reactions, and showed a tendency for improvement of liver function, METAVIR score, Child–Pugh score, MELD score, and quality of life for patients with liver cirrhosis.

Adipose-Derived Stem Cells: Current Applications and Future Directions in the Regeneration of Multiple Tissues

“…In these trials, ADSC transplantation did not raise any safety concerns. Besides, tests that measure liver function, such as the 13 C methacetin breath test, METAVIR score, Child-Pugh score, and MELD score, have yielded positive results [ 160 , 161 ]. Combined, these findings suggest that ADSC transplantation is a promising therapeutic option for the treatment of liver injury.…”

Immune and Metabolic Alterations in Liver Fibrosis: A Disruption of Oxygen Homeostasis?

“…Existing studies have shown that MSC therapy is prominently effective in hepatic fibrotic diseases indirectly by regulating the immune metabolism microenvironment (El Agha et al, 2017). The secretion of IL-17A from Th17 cells can promote fibrosis by activating fibroblasts (Huang et al, 2019;Hu et al, 2020). BM-MSCs inhibited liver fibrosis by decreasing the expression of IL-17A and IL-17RA and the serum levels of IL-17 in the liver (Farouk et al, 2018).…”

Allogeneic vs. autologous mesenchymal stem/stromal cells in their medication practice

“…The Laennec fibrosis scoring analysis following transplantation revealed that histological improvements were observed in 54.5% patients given 5 × 10 7 MSCs with 2 separate infusions and 4 weeks apart [ 112 ]. Similarly, clinical trials also showed that autologous BM-derived MSC administration reduced histological fibrosis and improved liver function in those patients with alcoholic cirrhosis [ 113 , 114 ]. Consequently, BM-derived MSC treatment can be a suitable option for fibrosis reduction and recovery from liver injury in patients with alcoholic cirrhosis.…”