Therapeutic potential of three-dimensional hepatocyte-like cells from human adipose-derived mesenchymal stem cells in urea cycle disorders.

Three-dimensional hepatocyte-like cells (3D HLCs) derived from human adipose-derived mesenchymal stem cells (ADSCs) represent a scalable and clinically accessible cell source for metabolic liver diseases. Here, the authors demonstrate that transplantation (Tx) of ADSC-derived 3D HLCs significantly enhances ammonia detoxification in vivo across multiple urea cycle disorder (UCD) models. 3D HLC Tx attenuated hyperammonemia, accelerated ammonia clearance, and improved encephalopathy-associated behavior in wild-type, ornithine transcarbamylase-deficient, and citrin-deficient mice. Engrafted human cells persisted and contributed to metabolic improvement. These findings highlight ADSC-derived 3D HLCs as a promising, minimally invasive therapeutic strategy and support their potential as an alternative to liver Tx for UCDs.