Autologous chemically induced liver progenitor cell transplantation ameliorates steatosis and fibrosis in a preclinical miniature pig model of metabolic dysfunction-associated fatty liver disease: A pilot study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disorder and can progress to steatohepatitis and fibrosis; although approved pharmacotherapies for metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis remain limited. Autologous chemically induced liver progenitor (CLiP) cells, generated from mature hepatocytes without genetic modification, have shown therapeutic promise in rodents, but their efficacy has not been tested in large animals. Six female Clawn miniature pigs (15-42 kg) were fed a high-fat, high-cholesterol diet to induce MASLD with biopsy-proven fibrosis (Brunt stage ≥1). Animals were assigned to CLiP transplantation (n = 3) or saline control (n = 3). Autologous CLiPs (5 × 107) were generated from laparoscopically resected liver wedges, expanded ex vivo, and infused intraportally. Safety was assessed by monitoring, liver function tests, and lipid profiles. Efficacy was evaluated 1 month later by blinded histology and immunohistochemistry. CLiP transplantation was feasible and well tolerated. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) showed minimal changes in both groups, but total cholesterol and triglycerides decreased in treated pigs and increased in controls. Histologically, two of three CLiP-treated livers regressed from Brunt stage 1 to 0, with resolution of steatosis and reduced stellate cell activation, whereas controls showed no regression. These findings support CLiP therapy as a regenerative option for MASLD.