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Annual Review of Physiology Feb 2023Liver regeneration occurs in response to diverse injuries and is capable of functionally reestablishing the lost parenchyma. This phenomenon has been known since... (Review)
Review
Liver regeneration occurs in response to diverse injuries and is capable of functionally reestablishing the lost parenchyma. This phenomenon has been known since antiquity, encapsulated in the Greek myth where Prometheus was to be punished by Zeus for sharing the gift of fire with humanity by having an eagle eat his liver daily, only to have the liver regrow back, thus ensuring eternal suffering and punishment. Today, this process is actively leveraged clinically during living donor liver transplantation whereby up to a two-thirds hepatectomy (resection or removal of part of the liver) on a donor is used for transplant to a recipient. The donor liver rapidly regenerates to recover the lost parenchymal mass to form a functional tissue. This astonishing regenerative process and unique capacity of the liver are examined in further detail in this review.
Topics: Animals; Humans; Liver Transplantation; Living Donors; Liver; Hepatectomy; Liver Regeneration; Homeostasis; Mammals
PubMed: 36270290
DOI: 10.1146/annurev-physiol-032822-094134 -
Blood Aug 2016Platelets have multiple functions beyond their roles in thrombosis and hemostasis. Platelets support liver regeneration, which is required after partial hepatectomy and... (Review)
Review
Platelets have multiple functions beyond their roles in thrombosis and hemostasis. Platelets support liver regeneration, which is required after partial hepatectomy and acute or chronic liver injury. Although it is widely assumed that platelets stimulate liver regeneration by local excretion of mitogens stored within platelet granules, definitive evidence for this is lacking, and alternative mechanisms deserve consideration. In-depth knowledge of mechanisms of platelet-mediated liver regeneration may lead to new therapeutic strategies to treat patients with failing regenerative responses.
Topics: Animals; Blood Platelets; Humans; Liver Regeneration; Models, Biological
PubMed: 27297793
DOI: 10.1182/blood-2016-04-692665 -
Current Opinion in Organ Transplantation Apr 2013Significant recent developments have occurred in the field of liver regeneration. Although the regenerative response to partial hepatectomy has been studied extensively,... (Review)
Review
PURPOSE OF REVIEW
Significant recent developments have occurred in the field of liver regeneration. Although the regenerative response to partial hepatectomy has been studied extensively, in recent years the use of new experimental approaches has incorporated a fresh look that may lead to a better understanding of hepatocyte dysfunction and regeneration.
RECENT FINDINGS
Liver injury promotes the regenerative responses that are relatively rare in healthy livers. Current research efforts focus on the mechanisms of hepatocyte adaptation in response to liver injury. We will discuss how hepatic aneuploidy and polyploidy contributes to liver regeneration, as well as new modalities to study cellular interactions using the organ-specific microenvironment.
SUMMARY
High mortality is generally limited to patients who develop terminal liver failure, which occurs when regenerative responses are unable to compensate for liver injury. Cellular adaptations and organ microenvironment changes are present during disease processes. This review aims to provide insights into the innovative approaches taken to investigate regeneration in liver diseases.
Topics: Hepatectomy; Hepatocytes; Humans; Liver; Liver Regeneration; Tissue Engineering
PubMed: 23425785
DOI: 10.1097/MOT.0b013e32835f07e2 -
Hepatobiliary & Pancreatic Diseases... Apr 2016Liver regeneration is a complex process. microRNAs (miRNAs) are short, single-stranded RNAs that modify gene expression at the post-transcriptional level. Recent... (Review)
Review
BACKGROUND
Liver regeneration is a complex process. microRNAs (miRNAs) are short, single-stranded RNAs that modify gene expression at the post-transcriptional level. Recent investigations have revealed that miRNAs are closely linked to liver regeneration.
DATA SOURCES
All included studies were obtained from PubMed, Embase, the ScienceDirect databases and Web of Science, with no limitation on publication year. Only studies published in English were considered.
RESULTS
We grouped studies that involved miRNA and liver regeneration into two groups: miRNAs as promoters and as inhibitors of liver regeneration. We summarized the relevant miRNAs separately from the related pathways.
CONCLUSIONS
Blocking or stimulating the pathways of miRNAs in liver regeneration may be novel therapeutic strategies in future regeneration-related liver managements. We may discover additional chemotherapy targets of miRNA.
Topics: Animals; Cell Proliferation; Gene Expression Regulation; Humans; Liver; Liver Regeneration; MicroRNAs; Signal Transduction
PubMed: 27020629
DOI: 10.1016/s1499-3872(15)60036-4 -
Medical Science Monitor : International... Dec 2020Liver regeneration (LR) is a set of complicated mechanisms between cells and molecules in which the processes of initiation, maintenance, and termination of liver repair... (Review)
Review
Liver regeneration (LR) is a set of complicated mechanisms between cells and molecules in which the processes of initiation, maintenance, and termination of liver repair are regulated. Although LR has been studied extensively, there are still numerous challenges in gaining its full understanding. Cells for LR have a wide range of sources and the feature of plasticity, and regeneration patterns are not the same under different conditions. Many patients undergoing partial hepatectomy develop cirrhosis or steatosis. The changes of LR in these cases are not clear. Many types of cells participate in LR. Hepatocytes, biliary epithelial cells, hepatic progenitor cells, and human liver stem cells can serve as the cell sources for LR. However, different types and degrees of damage trigger the response from the most suitable cells. Exploring the cell sources of LR is of great significance for accelerating recovery of liver function under different pathological patterns and developing a cell therapy strategy to cope with the shortage of donors for liver transplantation. In clinical practice, the background of the liver influences regeneration. Fibrosis and steatosis create different LR microenvironments and signal molecule interaction patterns. In addition, factors such as partial hepatectomy, aging, platelets, nerves, hormones, bile acids, and gut microbiota are widely involved in this process. Understanding the influencing factors of LR has practical value for individualized treatment of patients with liver diseases. In this review, we have summarized recent studies and proposed our views. We discuss cell sources and the influential factors on LR to help in solving clinical problems.
Topics: Animals; Gastrointestinal Microbiome; Hepatocytes; Humans; Liver Regeneration; Signal Transduction; Stem Cell Niche; Stem Cells
PubMed: 33311428
DOI: 10.12659/MSM.929129 -
Revista Espanola de Enfermedades... Mar 2014Liver regeneration (LR) is one of the most amazing tissue injury response. Given its therapeutic significance has been deeply studied in the last decades.LR is an... (Review)
Review
Liver regeneration (LR) is one of the most amazing tissue injury response. Given its therapeutic significance has been deeply studied in the last decades.LR is an extraordinary complex process, strictly regulated, which accomplishes the characteristics of the most evolutionary biologic systems (robustness) and explains the difficulties of reshaping it with therapeutic goals.TH reproduces the physiological tissue damage response pattern, with a first phase of priming of the hepatocytes-cell-cycle transition G0-G1–, and a second phase of proliferation –cell-cycleS/M phases– which ends with the liver mass recovering. This process has been related with the tissue injury response regulators as: complement system, platelets, inflammatory cytokines(TNF-a, IL-1b, IL-6), growth factors (HGF, EGF, VGF) and anti-inflammatory factors (IL-10, TGF-b).Given its complexity and strict regulation, illustrates the unique alternative to liver failure is liver transplantation.The recent induced pluripotential cells (iPS) description and the mesenchymal stem cell (CD133+) plastic capability have aroused new prospects in the cellular therapy field. Those works have assured the cooperation between mesenchymal and epithelial cells. Herein, we review the physiologic mechanisms of liver regeneration.
Topics: Animals; Cytokines; Hepatitis; Humans; Liver Diseases; Liver Regeneration
PubMed: 25007016
DOI: No ID Found -
Cellular and Molecular Gastroenterology... 2022Liver sinusoidal endothelial cells (SECs) promote the proliferation of hepatocytes during liver regeneration. However, the specific subset of SECs and its mechanisms...
BACKGROUND & AIMS
Liver sinusoidal endothelial cells (SECs) promote the proliferation of hepatocytes during liver regeneration. However, the specific subset of SECs and its mechanisms during the process remain unclear. In this study, we investigated the potential role of c-kit SECs, a newly identified subset of SECs in liver regeneration.
METHODS
Partial hepatectomy mice models were established to induce liver regeneration. Hepatic c-kit expression was detected by quantitative reverse-transcription polymerase chain reaction, immunofluorescent staining, and fluorescence-activated cell sorting. VE-cadherin-cyclization recombinase-estrogen receptor (Cdh5-Cre-ERT) Notch intracellular domain and Cdh5-Cre recombination signal binding protein Jκ mice were introduced to mutate Notch signaling. c-Kit SECs were isolated by magnetic beads. Single-cell RNA sequencing was performed on isolated SECs. Liver injuries were induced by CCl or quantitative polymerase chain reaction injection.
RESULTS
Hepatic c-kit is expressed predominantly in SECs. Liver resident SECs contribute to the increase of c-kit during partial hepatectomy-induced liver regeneration. Isolated c-kit SECs promote hepatocyte proliferation in vivo and in vitro by facilitating angiocrine. The distribution of c-kit shows distinct spatial differences that are highly coincident with the liver zonation marker wingless-type MMTV integration site family, member2 (Wnt2). Notch mutation reshapes the c-kit distribution and liver zonation, resulting in altered hepatocyte proliferation. c-Kit SECs were shown to regulate hepatocyte regeneration through angiocrine in a Wnt2-dependent manner. Activation of the Notch signaling pathway weakens liver regeneration by inhibiting positive regulatory effects of c-kit SECs on hepatocytes. Furthermore, c-kit SEC infusion attenuates toxin-induced liver injuries in mice.
CONCLUSIONS
Our results suggest that c-kit SECs contributes to liver zonation and regeneration through Wnt2 and is regulated by Notch signaling, providing opportunities for novel therapeutic approaches to liver injury in the future. Transcript profiling: GEO (accession number: GSE134037).
Topics: Animals; Endothelial Cells; Hepatectomy; Hepatocytes; Liver; Liver Regeneration; Mice
PubMed: 35114417
DOI: 10.1016/j.jcmgh.2022.01.019 -
Pharmacological Reviews May 2024The liver has the unique capacity to regenerate, and up to 70% of the liver can be removed without detrimental consequences to the organism. Liver regeneration is a... (Review)
Review
The liver has the unique capacity to regenerate, and up to 70% of the liver can be removed without detrimental consequences to the organism. Liver regeneration is a complex process involving multiple signaling networks and organs. Liver regeneration proceeds through three phases: the initiation phase, the growth phase, and the termination phase. Termination of liver regeneration occurs when the liver reaches a liver-to-body weight that is required for homeostasis, the so-called "hepatostat." The initiation and growth phases have been the subject of many studies. The molecular pathways that govern the termination phase, however, remain to be fully elucidated. This review summarizes the pathways and molecules that signal the cessation of liver regrowth after partial hepatectomy and answers the question, "What factors drive the hepatostat?" SIGNIFICANCE STATEMENT: Unraveling the pathways underlying the cessation of liver regeneration enables the identification of druggable targets that will allow us to gain pharmacological control over liver regeneration. For these purposes, it would be useful to understand why the regenerative capacity of the liver is hampered under certain pathological circumstances so as to artificially modulate the regenerative processes (e.g., by blocking the cessation pathways) to improve clinical outcomes and safeguard the patient's life.
Topics: Liver Regeneration; Humans; Animals; Signal Transduction; Liver; Hepatectomy
PubMed: 38697856
DOI: 10.1124/pharmrev.123.000955 -
The American Journal of Pathology Jan 2010Liver regeneration after partial hepatectomy is one of the most studied models of cell, organ, and tissue regeneration. The complexity of the signaling pathways... (Review)
Review
Liver regeneration after partial hepatectomy is one of the most studied models of cell, organ, and tissue regeneration. The complexity of the signaling pathways initiating and terminating this process have provided paradigms for regenerative medicine. Many aspects of the signaling mechanisms involved in hepatic regeneration are under active investigation. The purpose of this review is to focus on the areas still not well understood. The review also aims to provide insights into the ways by which current concepts of liver regeneration can provide understanding regarding malfunction of the regenerative process in liver diseases, such as acute liver failure.
Topics: Animals; Biomechanical Phenomena; Hepatectomy; Humans; Intercellular Signaling Peptides and Proteins; Liver Regeneration; Regional Blood Flow; Signal Transduction
PubMed: 20019184
DOI: 10.2353/ajpath.2010.090675 -
Khirurgiia 2021Liver is an exceptional organ due to unique anatomical and physiological features, as well as advanced regenerative ability. Discovery of molecular mechanisms governing...
Liver is an exceptional organ due to unique anatomical and physiological features, as well as advanced regenerative ability. Discovery of molecular mechanisms governing liver regeneration allowed researchers to use them to enhance liver regeneration. However, significant progress in this area was achieved through the introduction of gene therapy. In this manuscript, the authors consider stem cells for cell therapy and tissue engineering, as well as an alternative to liver transplantation.
Topics: Cell- and Tissue-Based Therapy; Humans; Liver; Liver Regeneration; Stem Cells; Tissue Engineering
PubMed: 33570361
DOI: 10.17116/hirurgia202102188