Research Associate Shanghai Institute of Biochemistry and Cell Biology (SIBCB) Shanghai, Shanghai, China
Abstract: Alginate-encapsulated hepatocyte transplantation represents a promising universal hepatocyte cell therapy for treating liver failure. However, its clinical application has been limited by the scarcity of primary human hepatocytes (PHH). We previously generated proliferating human hepatocytes (ProliHH) through dedifferentiation of PHH and engineered them into encapsulated liver organoids (eLO), providing an unlimited cell source for transplantation. The preclinical efficacy and safety of eLOs have been demonstrated in mouse models in our previous study. Here, we report the large-scale manufacturing of eLOs under GMP conditions. Furthermore, we assessed the safety of the surgical procedure by transplanting clinical-scale eLOs under ultrasound guidance in dogs and pigs, demonstrating that the transplantation had no adverse effects on the animals. Based on these preclinical data, we conducted an investigator-initiated study to evaluate the feasibility and safety of eLO transplantation in patients with liver failure. Four patients with chronic liver failure or acute-on-chronic liver failure were successfully enrolled. Three of them had completed the six-month follow-up, demonstrating good tolerance to eLO transplantation. Notably, patient #1 and #3 showed improved liver functions, including increased albumin, reduced total bilirubin (TBIL) and ammonia levels, and improved INR. Collectively, these findings provide preliminary evidence supporting the safety and potential efficacy of eLO transplantation for liver failure.
