Hepatic Regeneration in Cirrhosis

Abstract

End-stage liver disease is characterized by massive hepatocyte death resulting in clinical decompensation and organ failures. Clinical consequences in cirrhosis are the results of the loss of functional hepatocytes and excessive scarring. The only curative therapy in advanced cirrhosis is orthotropic liver transplantation, but the clinical demand outweighs the availability of acceptable donor organs. Moreover, this also necessitates lifelong immunosuppression and carries associated risks. The liver has a huge capability for regeneration. Self-replication of quiescent differentiated hepatocytes and cholangiocytes occurs in patients with acute liver injury. Due to limited hepatocyte self-renewal capacity in advanced cirrhosis, great interest has therefore been shown in characterizing the possible role of hepatic progenitor cells and bone marrow-derived stem cells to therapeutically aid this process. Transplantation of cells from various sources that can be properly differentiated into functional liver cells or use of growth factors for ex-vivo expansion of progenitor cells is needed at utmost priority. Multiple researches over the last two decades have aided researchers in refining proliferation, differentiation, and storage techniques and understand the functionality of these cells for use in clinical practice. However, these cell-based therapies are still experimental and have to be used in trial settings.

Keywords: Ang2, angiopoietin 2; BM, Bone marrow; BM-MNCs, bone marrow mononuclear cells; BMSC, bone marrow stem cells; DAMPs, Damage associated molecular patterns; EPCs, endothelial progenitor cells; ESRP2, epithelial splicing regulatory protein 2; GCSF; HGF, hepatocyte growth factor; HPC, Hepatocyte progenitor cells; HSCs, hematopoietic stem cells; Hh, Hedgehog; HybHP, hybrid periportal hepatocytes; MMP, matrix metalloprotease; MSCs, mesenchymal stromal cells; OLT, Orthotropic liver transplantation; PAMPs, Pathogen associated molecular patterns; SAH, severe alcoholic hepatitis; SDF1, stromal-derived factor 1; TNFSF12, tumor necrosis factor ligand superfamily member 12; Terthigh, high Telomerase reverse transcriptase; [Hnf4a], Hepatocyte Nuclear Factor 4 Alpha; [Mfsd2a], Major Facilitator Superfamily Domain containing 2A; acute liver failure; chronic liver diseases; hepatocyte transplant; liver regeneration.