The role of stem cells in liver injury and repair

Boyd, Alexander; Newsome, Philip N.; Lu, Wei-Yu

doi:10.1080/17474124.2019.1618186

Cited by 15 publications

(13 citation statements)

References 94 publications

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“…Multiple progenitor markers have been proposed, but none are completely specific as recent studies demonstrate that liver progenitors are actually a heterogeneous population that contains a variety of cell types, ranging from more primitive progenitors to more differentiated cells (eg, hepatocyte-like). Indeed, in adult mice, progenitors include biliary-like cells (also known as ‘oval cells’ in rodents) which arise in the ductal region, as well as progenitors around the central vein, de-differentiated hepatocytes or cholangiocytes, as well as multipotent mesenchymal stem cells (MSC) which also exhibit immunomodulatory properties 3 4. Similar heterogeneity has now been described in humans: EpCam+/NCAM+bi-potent progenitors reside the ductal plate of the human fetal liver and are subsequently retained in the Canals of Herring of the adult liver, and these latter cells co-express genes associated with both hepatic and biliary lineage (eg, SOX9, HNF1B, K19, CD24, CD133, K7 and OPN) 4.…”

mentioning

confidence: 88%

“…In adults, after an acute liver injury, ‘normal’ regeneration occurs through the proliferation and expansion of remaining healthy hepatocytes and cholangiocytes, and there is minimal involvement of liver progenitors. By contrast, repair during chronic liver injury involves the proliferation of progenitor cells and cells with certain stem-like properties to differentiate into both hepatocytes and cholangiocytes, and thus support the restoration of liver function 2 3. What are the identity and/or origin of these liver progenitors?…”

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confidence: 99%

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Harnessing liver progenitors in the treatment of liver fibrosis: a step in the right direction?

Breitkopf‐Heinlein

Syn

2020

Gut

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mentioning

confidence: 88%

mentioning

confidence: 99%

Harnessing liver progenitors in the treatment of liver fibrosis: a step in the right direction?

Breitkopf‐Heinlein

Syn

2020

Gut

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“…This can result in very complex combinations regarding cell types and products used, origin (endogenous or exogenous), additional manipulation in the laboratory, dosage, single, or multiple doses, route of administration, time of intervention, and comorbidities. All these factors can result in higher costs and standards of care to enable the clinical use of cell therapy [19]. Still, once positive outcomes are reached by a refined technique in preclinical phases, cell therapy is likely to be cost-effective and beneficial.…”

Section: Cell Types Used For the Inhibition Of Liver Fibrosismentioning

confidence: 99%

Mechanisms Underlying Cell Therapy in Liver Fibrosis: An Overview

Pinheiro

Dias

Silva

et al. 2019

Cells

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Fibrosis is a common feature in most pathogenetic processes in the liver, and usually results from a chronic insult that depletes the regenerative capacity of hepatocytes and activates multiple inflammatory pathways, recruiting resident and circulating immune cells, endothelial cells, non-parenchymal hepatic stellate cells, and fibroblasts, which become activated and lead to excessive extracellular matrix accumulation. The ongoing development of liver fibrosis results in a clinically silent and progressive loss of hepatocyte function, demanding the constant need for liver transplantation in clinical practice, and motivating the search for other treatments as the chances of obtaining compatible viable livers become scarcer. Although initially cell therapy has emerged as a plausible alternative to organ transplantation, many factors still challenge the establishment of this technique as a main or even additional therapeutic tool. Herein, the authors discuss the most recent advances and point out the corners and some controversies over several protocols and models that have shown promising results as potential candidates for cell therapy for liver fibrosis, presenting the respective mechanisms proposed for liver regeneration in each case.

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“…Каждое из этих состояний нарушает нормальные регенеративные пути и/или инициирует апоптоз, что приводит к нарушению функций гепатоцитов после частичной гепатэктомии. Предпринимаемые усилия по разработке и внедрению новых методов по активации регенерации печени не всегда являются эффективными [8,9,10].…”

Section: Introductionunclassified

Influence of combined transplantation of multipotent mesenchymal stromal cells and stellate liver cells on its morphofunctional state after partial hepatectomy

Maklakova

Grebnev

Osipenko

2021

jour

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The aim of the study was to study the changes in the morphofunctional state of the liver after the combined transplantation of multipotent mesenchymal stromal (MMSC) and stellate liver cells (ZCP) in animals with partial hepatectomy.Materials and methods. The MMSC culture was isolated from the placental chorion of 5 laboratory animals f female mice aged 3-4 months, weighing 22-23 g, gestation period of 18 days. The mononuclear fraction of the cells was obtained by sequential mechanical and enzymatic treatment of the placental tissue. The cultivation of MMSCs was carried out in a CO2 incubator at a temperature of 37 0C with a carbon dioxide content of 5% and a humidity of 90%. ZCP was isolated by collagenase-pronase perfusion of the liver, followed by cell separation in the histodense density gradient. MMSCs of the 3rd passage were introduced, and ZKP was introduced immediately after isolation. MMSCs at a dose of 4 million cells/kg and ZCP at a dose of 9 million cells/ kg were used for transplantation to labotory animals. The cells were injected 1 hour after partial hepatectomy. The biochemical parameters of peripheral blood and morphometric parameters of the liver were evaluated on the 3rd, 7th day after the administration of MMSC.Results. As a result of the study, it was found that the combined transplantation of MMSC and ZCP after partial hepatectomy leads to the restoration of the level of enzymes that characterize cytolysis and cholestasis, normalization of the protein-synthetic function of the liver, normalization morphometric parameters of the liver. A significant mechanism for restoring the morphofunctional state of the liver can be considered the influence of transplanted MMSCs and ZCP on the cell repair system, which leads to a decrease in the severity of programmed cell death of hepatocytes and the level of pathological mitoses.Discussion. Combined transplantation of MMSCs and HCP after partial hepatectomy leads to an increase in the level of hepatocyte growth factor (HGF), thus contributing to an se in the mitotic activity of hepatocytes and the restoration of liver mass. The transplanted cells also, by increasing the activity of DNA repair enzymes of the PARP family, lead to a decrease in the level of pathological mitoses, inhibition of their programmed cell death.Conclusions. The conducted studies demonstrate the ability of combined MMSC and PCR transplantation to restore the morphofunctional state of the liver after partial hepatectomy and provide the basis for conducting pilot clinical studies

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The role of stem cells in liver injury and repair

Cited by 15 publications

References 94 publications

Harnessing liver progenitors in the treatment of liver fibrosis: a step in the right direction?

Harnessing liver progenitors in the treatment of liver fibrosis: a step in the right direction?

Mechanisms Underlying Cell Therapy in Liver Fibrosis: An Overview

Influence of combined transplantation of multipotent mesenchymal stromal cells and stellate liver cells on its morphofunctional state after partial hepatectomy

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