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Understanding the marvels behind liver regeneration

Overview

Anan Abu Rmilah, Wei Zhou, Erek Nelson, Li Lin, Bruce Amiot, Scott L. Nyberg

Published Online: Mar 28 2019

DOI: 10.1002/wdev.340

Full article on Wiley Online Library: HTML PDF

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Tissue regeneration is a process by which the remaining cells of an injured organ regrow to offset the missed cells. This field is relatively a new discipline that has been a focus of intense research by clinicians, surgeons, and scientists for decades. It constitutes the cornerstone of tissue engineering, creation of artificial organs, and generation and utilization of therapeutic stem cells to undergo transformation to different types of mature cells. Many medical experts, scientists, biologists, and bioengineers have dedicated their efforts to deeply comprehend the process of liver regeneration, striving for harnessing it to invent new therapies for liver failure. Liver regeneration after partial hepatectomy in rodents has been extensively studied by researchers for many years. It is divided into three important distinctive phases including (a) Initiation or priming phase which includes an overexpression of specific genes to prepare the liver cells for replication, (b) Proliferation phase in which the liver cells undergo a series of cycles of cell division and expansion and finally, (c) termination phase which acts as brake to stop the regenerative process and prevent the liver tissue overgrowth. These events are well controlled by cytokines, growth factors, and signaling pathways. In this review, we describe the function, embryology, and anatomy of human liver, discuss the molecular basis of liver regeneration, elucidate the hepatocyte and cholangiocyte lineages mediating this process, explain the role of hepatic progenitor cells and elaborate the developmental signaling pathways and regulatory molecules required to procure a complete restoration of hepatic lobule. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration Signaling Pathways > Global Signaling Mechanisms Gene Expression and Transcriptional Hierarchies > Cellular Differentiation

Microscopic anatomy of human liver

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Structural regeneration of hepatic lobule after partial hepatectomy

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Interaction between different liver cells during liver regeneration after partial hepatectomy

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Contribution of growth factors in liver regeneration

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Molecular pathways underying liver regeneration process

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Temporal sequence of events of liver regeneration after partial hepatectomy

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Partial hepatectomy in rodent liver

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(a) The development of pars hepatica and pars cystica. (b) Pars hepatica gives rise to the hepatic duct and liver parenchyma whereas pars cystica gives rise to cystic duct and gall bladder

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(a) The primitive gut differentiation and hepatic bud development by the endodermal part of foregut. (b) The penetration of hepatic cords into the septum transversum

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