Cell therapy in chronic liver disease

Abstract

Purpose of review To date, the only curative treatment for end-stage liver disease is liver transplantation, which is limited by the shortage of available organs. Cell therapy, in the form of cell transplantation or cell-based extracorporeal support devices, may in the future offer an alternative to transplantation, or at least provide liver function support as a bridging therapy until surgery may be performed. The purpose of this review is to highlight the most recent advances made in the field of cell therapy and regenerative medicine for the treatment of chronic liver disease (CLD). Recent findings After hepatocyte transplantation, long-term engraftment in the liver and spleen may be achieved, which can be stimulated through preconditioning, multiple infusions, and inflammatory response blockade. Mesenchymal stem cells are promising candidates for cell transplantation, as they have been shown to reduce liver fibrosis and support endogenous regeneration. Adipose tissue-derived stem cells are also being tested in this setting, due to their ready availability. Bioartificial liver (BAL) devices are being built that allow for effective preservation of hepatocytes, and one such device has recently demonstrated survival benefit in a porcine model of liver failure. Summary Cell transplantation of primary hepatocytes or stem cell-derived hepatocyte-like cells (HLCs) for the treatment of CLD holds promise. BAL systems may in the future be able to bridge acute-on-chronic liver failure patients to liver transplantation.

Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets

“…During chronic liver disease, ongoing liver injury results in excessive ECM deposition with limited remodeling, which inevitably leads to scarring and fibrosis[5]. In comparison, the liver can quickly re-establish its structural integrity in response to acute injury, even when a substantial portion of the organ is damaged[6]. …”

Concise Review: Liver Regenerative Medicine: From Hepatocyte Transplantation to Bioartificial Livers and Bioengineered Grafts

“…The most important restriction to their use, however, is the difficulty that isolation of a sufficient quantity of metabolically active, high quality cells presents . Not only is there a universal shortage of donor livers on which cell harvests may be performed, but the fact that hepatocytes are typically harvested from livers not suitable for transplantation makes quantity and quality of cells obtained highly variable . Alternatives to the use of primary human hepatocytes are porcine hepatocytes and stem cell‐derived HLCs.…”

Regenerative Medicine and the Biliary Tree

“…39,40 Regenerative strategy refers to the engraftment of progenitor cells that require in vivo growth and differentiation (stem cell transplant is an example). 17,41,42 Rejuvenation strategy refers to the induction of self-renewal of tissues by the activation of endogenous stem cells. [43][44][45] In the context of biliary disease, replacement would include therapies designed to directly replace the damaged biliary epithelium (e.g., cholangiocyte-based cell therapies, bioengineered tissue patches, etc.).…”