Functional characterization of urine-derived stem cells from acute-on-chronic liver failure patients in an immune-mediated acute liver injury model.

INTRODUCTION

Acute-on-chronic liver failure (ACLF) is a highly lethal clinical syndrome with limited effective therapeutic options. Urine-derived stem cells (USCs) represent a non-invasive and readily accessible cell source, but whether USCs obtained from patients with severe liver dysfunction retain therapeutic and immunomodulatory potential remains unclear.

METHODS

To address this question, USCs derived from ACLF patients (LF-USCs) were evaluated in a Concanavalin A (Con A)-induced immune-mediated acute liver injury mouse model. Hydrogel-encapsulated LF-USCs were transplanted, and therapeutic efficacy was assessed by survival analysis, serum biochemical parameters, histological examination, and inflammatory cytokine profiling.

RESULTS

Transplantation of hydrogel-encapsulated LF-USCs significantly improved mouse survival, reduced serum transaminase levels, and alleviated hepatocellular necrosis (p < 0.05). At the mechanistic level, LF-USC treatment was associated with decreased systemic inflammatory cytokine levels, attenuation of intrahepatic inflammatory injury, and dynamic modulation of macrophage-associated inflammatory signatures.

DISCUSSION: These findings demonstrate that functionally competent USCs can be successfully obtained from ACLF patients and highlight their potential as a readily accessible autologous cell source for immune modulation and liver tissue repair in immune-mediated acute liver injury.