Some studies have successfully applied iPSC-derived cholangiocyte organoid platforms to screen and repurpose drugs in CF. For example, in the case of AATD, transplanted cells must engraft, survive long-term, and integrate with the host vasculature to support the secretion of alpha-1 antitrypsin (AAT) into the bloodstream.Ĭould Organoid Cultures Help Better Understand Alagille Syndrome?Ĭholangiocyte organoids have also been used to study biliary abnormalities in several diseases, including ALGS, cystic fibrosis (CF), and cholangiocarcinoma (CC). It is essential that cells meet high-quality standards to be successfully used in liver regenerative medicine.

Patient-derived hepatocyte organoids have been used to create disease models for Alagille syndrome (ALGS) and alpha-1 antitrypsin deficiency (AATD), among other diseases. So far, only iPSC-derived hepatocyte organoids have been developed. iPSC- and adult stem cell-derived cholangiocyte organoids engraft but do not rescue animal models of biliary injury.Įctopic transplantation of multicellular liver organoids, the so-called “mini-livers,” might be essential in cases of end-stage organ damage, when hepatocyte transplantation fails to fully restore the liver function due to a hostile microenvironment.Primary hepatocytes are more suitable for diseases that affect primarily hepatocytes as they remain committed to the hepatic lineage.Adult stem cell-derived organoids are more suitable for diseases that affect hepatic and biliary compartments as they theoretically can regenerate both.Hepatocyte- and adult stem cell-derived organoids are less prone to genetic instability and might have higher differentiation efficiency than iPSC-derived organoids, but are more difficult to obtain due to restricted access to primary tissue.As discussed by Jalan-Sakrikar and colleagues, each system has advantages and limitations that should be carefully weighed against its final application: Several studies used organoids derived from induced pluripotent stem cells (iPSCs), adult stem cells, or primary tissue to regenerate hepatocellular parenchyma (hepatocellular organoids) and bile ducts (cholangiocyte organoids). Liver Organoids Present New Opportunities in Medical Researchĭifferent types of liver organoids have been used for research and clinical purposes. Organoids) and/or resembles counterpart tissues in vivo (eg, primary organoids),” Jalan-Sakrikar et al wrote. “Organoids, in the modern context, can be definedĪs 3D structures, grown in vitro from stem/progenitor cells or primary tissue, that self-organize in an organotypic manner through spatio-temporal patterning that may recapitulate developmental stages (eg, stem cell-derived The concept of organoids has evolved since their first use. Regenerative medicine involves replacement using a cell-based approach such as liver organoids, regeneration, and rejuvenation. They are not conditioned by the availability of a healthy organ donor they avoid the use of immunosuppression, as they can use autologous cells and they can surpass the need for surgery, and, consequently, postoperative complications since cells can be administered as an infusion. When compared with conventional liver transplantation, these approaches have several advantages. Replace the damaged cells or tissues with healthy ones, in an autologous or allogeneic manner, when the liver no longer has endogenous regenerative capacity or the damage is irreversible.Promote endogenous tissue repair and regeneration to reverse liver disease before irreversible damage occurs.

Induced pluripotent stem cells