Cell Transplantation

Liver cell therapy (LCT) is a procedure where cells rather than organs are transplanted in a patient affected by a liver-based inborn error of metabolism (IEM) or an acquired liver disease. It has been developed to overcome the limitations of liver transplantation (LT), mainly organ shortage. Initially, fresh hepatocytes isolated from livers not suitable for LT were used to treat, for the most part, liver-based IEM such as urea cycle disorders or Crigler-Najjar syndrome type 1. Hepatocyte transplantation (HT) led to encouraging biochemical and clinical results, but these were limited in time. Preirradiation of the native liver, repeated infusions, and optimized immunosuppression protocols partially improved the clinical outcome presenting HT as a bridge to transplantation procedure in at least half of the published pediatric cases (30/58). Along with hepatocytes, stem cells—comprised of mesenchymal stromal cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs)—have been evaluated for LCT. These cells proliferate in vitro; they resist cryopreservation but fail to express the complete hepatocyte metabolic functionality and so are better indicated for acquired liver diseases. Stem cells probably act mostly on liver inflammation, fibrosis, and regeneration through their secretome. Tissue engineering strategies (e.g., culture on thermosensitive polymer, three-dimensional cell culture, coculture on scaffolds and bioprinted organs) are currently under evaluation in the laboratory but their use in the clinic is still not standardized.