The origin, marker, regulation and therapeutic potential of hepatic oval cells / 复旦学报（医学版）

The liver plays an vital role in glucose and lipid metabolism,synthesis of plasma proteins,and detoxification of xenobiotics.Liver chronic disease is one of the leading causes of death in China.Liver mass can be restored by two mechanisms:division of hepatocytes and hepatic oval cells (HOCs) proliferation and differentiation.However,the origin,specific markers and signaling pathways of HOCs have not been fully elucidated.Recent researches in HOCs isolation methods and genetic lineage tracing have enabled investigators to study multiple aspects of HOCs origin and biology.We reviewed the previous researches in detail.

Histone deacetylase inhibition induced epithelial-mesenchymal transition by Snail in hepatic oval cells / 中华肝胆外科杂志

Objective Epithelial mesenchymal transition (EMT) has a role in the proliferation and metastasis of various types of cells.This study investigates the hepatic oval cell's mechanism of EMT induced by histone deacetylase inhibition and the resulting cell motility increase from EMT.Methods Hepatic oval cell stem cell markers and marker changes were detected by flow cytometry,and after histone deacetylase inhibition induced EMT,the morphological changes were recorded.Western blot and quantitative real-time polymerase chain reaction detected the expression of E-cadherin,vimentin and Snail.Furthermore,confocal microscopy analysis recognized the nuclear translocation of Snail.Results Flow cytometry revealed no changes in the stem cell properties of hepatic oval cells in the cell culture process.Oval cell EMT,induced by HDACi,was observed through morphological changes,a reduction of the epithelial cell marker E cadherin,and an increase of the mesenchymal cell marker Vimentin.HDACi can promote the expression and nuclear translocation of Snail,which is the key hepatic oval cell transcription factor for both EMT and enhanced motility.Therefore,Snail RNA interference can suppress HDACi induced EMT in hepatic oval cells.Conclusions In conclusion,histone deacetylase inhibition induces hepatic oval cell epithelial-mesenchymal transition by Snail.

The function of hepatic oval cells under high glucose condition in vivo / 中华内分泌代谢杂志

Rat hepatic oval cell model was induced by hyperglycemia and streptozotocin in vivo. Expression of insulin and mRNA expression of pancreatic transcription factors(Nkx6.1, PDX-1) were carried out. It showed that under high glucose, liver tissues were positive for insulin staining, the expression of Nkx6.1 and Pdx-1mRNA was significantly enhanced, and insulin-1mRNA was found to be expressed. The result suggests that under high glucose, hepatic oval cells can differentiate into insulin-producing cells.

Research progress on hepatic oval cells / 解剖学报

Hepatic oval cells (OCs) are the stem cells of the liver. They can differentiate into liver cells, bile duct epithelial cells and other cells, and also are closely related to liver regeneration and liver diseases. In this article, we give a brief summary focused on the source, location, proliferation, differentiation, apoptosis, transplantation of hepatic oval cells, and its role in liver regeneration and liver diseases.

Clinical application of stem cells in liver diseases / 대한간학회지

Most liver diseases lead to hepatic dysfunction with organ failure. Liver transplantation is the best curative therapy, but it has some limitations such as donor shortage, possibility of rejection, and maintenance of immunosuppressant. New therapies have been actively searched for over several decades, primarily in the form of artificial liver support devices and hepatocyte transplantation, but both of these modalities remain experimental. Stem cells have recently shown promise in cell therapy because they have the capacity for self-renewal and multilineage differentiation, and are applicable to human diseases. Very recent reports of unexpected plasticity in adult bone marrow have raised hopes of stem cell therapy offering exciting therapeutic possibilities for patients with chronic liver disease. Both rodent and human embryonic stem cells, bone marrow hematopoietic stem cells, mesenchymal stem cells, umbilical cord blood cells, fetal liver progenitor cells, adult liver progenitor cells, and mature hepatocytes have been reported to be capable of self-renewal, giving rise to daughter hepatocytes both in vivo and in vitro. These cells can repopulate livers in animal models of liver injury and appear to be able to improve liver function. However, significant challenges still exist before these cells can be used in humans, such as the lack of consensus about the immunophenotype of liver progenitor cells, uncertainty of the physiological role of reported candidate stem/progenitor cells, practicality of obtaining sufficient quantity of cells for clinical use, and concerns over ethics, long-term efficacy, and safety. There have been reports of phase 1 trials using stem cell transplantation in humans for liver diseases, but more effective trials are needed. We review the use of stem cells (focusing on adult ones) and the reported human clinical trials, and highlight the challenges facing clinicians in their quest to use liver stem cells to save lives.

Research Progress and Clinical Value of Hepatic Stem Cells and Its Relations with Liver Cancer / 中国普外基础与临床杂志

Objective To investigate the clinical outlook of hepatic stem cells and its relations with liver cancer. Methods The literatures of recent years on the studies of hepatic stem cells were reviewed. Results Liver cancer may consist of cells of various differentiation grades and it may result from the perodifferentiated hepatic stem cells or abnormal differentiated cells. Conclusion The hypothesis of hepatic stem cells has been identified extensively. Further study maybe helpful for revealing the origin, carcinogenesis of hepatic cancer, and may also be useful for the understanding of the mechanism of metastasis.