Abstract:The liver has a marked capacity for regeneration. In most cases the liver regeneration is determined by hepatocytes. The regenerative capacity of hepatocytes is significantly reduced in acute or chronic damage. In particular, repair mechanisms are not activated in patients with alcoholic cirrhosis. Organ transplantation or advanced methods of regenerative medicine can help such patients. The promising results were obtained in clinical trials involving patients with various forms of liver disease who received t… Show more
“…For example, Najimi et al [20] found that 99% of liver MSCs were positive for CD90, 92% of the cells were positive for CD73, 88% were positive for CD29, 92% for CD44, and 76% for HLA-Class I. In our work, we showed by flow cytometry that only about 30% of liver MSCs isolated from the liver of patients with cirrhosis and fibrosis expressed CD90 and CD44 [33]. Moreover, a gene expression microarray confirmed that the expression level of CD90 ( THY1 ) was low, while the expression level of CD44 was very high (our unpublished data; see Table 1).…”
Section: Morphology and Phenotype Of Human Liver Mscssupporting
confidence: 49%
“…As with MSCs isolated from other sources, liver MSCs do not express markers of hematopoietic and endothelial cells, such as CD11b, CD14, CD19, CD31, CD34, CD45, CD79β, CD117, CD133, CD144, and HLA-DR [20,23,27,33,36]. The lack of expression of CD34, CD45, and CD117 on the surface of liver MSCs suggests that these cells are not so-called hepatic progenitor cells (the human counterpart to rodent oval cells) which are bipotent resident hepatic cells that can differentiate into hepatocytes and cholangiocytes [28,38].…”
Section: Morphology and Phenotype Of Human Liver Mscsmentioning
confidence: 99%
“…Several research groups using different differentiation protocols (Table 3) have demonstrated the ability of human liver MSCs to differentiate into hepatocyte-like cells in vitro [20,21,27,33,34,72,94]. The opposite was reported in just one paper by Porretti et al [92] claiming that cultured CD105 + CD73 + Thy-1 + CD45 − CD34 − MSCs obtained from the mononuclear fraction of the liver after removal of hepatocytes did not differentiate into the endothelial and hepatic lineages.…”
Section: Properties and Therapeutic Potential Of Human Liver Mscsmentioning
Chronic liver diseases constitute a significant economic, social, and biomedical burden. Among commonly adopted approaches, only organ transplantation can radically help patients with end-stage liver pathologies. Cell therapy with hepatocytes as a treatment for chronic liver disease has demonstrated promising results. However, quality human hepatocytes are in short supply. Stem/progenitor cells capable of differentiating into functionally active hepatocytes provide an attractive alternative approach to cell therapy for liver diseases, as well as to liver-tissue engineering, drug screening, and basic research. The application of methods generally used to isolate mesenchymal stem cells (MSCs) and maintain them in culture to human liver tissue provides cells, designated here as liver MSCs. They have much in common with MSCs from other tissues, but differ in two aspects—expression of a range of hepatocyte-specific genes and, possibly, inherent commitment to hepatogenic differentiation. The aim of this review is to analyze data regarding liver MSCs, probably another type of liver stem/progenitor cells different from hepatic stellate cells or so-called hepatic progenitor cells. The review presents an analysis of the phenotypic characteristics of liver MSCs, their differentiation and therapeutic potential, methods for isolating these cells from human liver, and discusses issues of their origin and heterogeneity. Human liver MSCs are a fascinating object of fundamental research with a potential for important practical applications.
“…For example, Najimi et al [20] found that 99% of liver MSCs were positive for CD90, 92% of the cells were positive for CD73, 88% were positive for CD29, 92% for CD44, and 76% for HLA-Class I. In our work, we showed by flow cytometry that only about 30% of liver MSCs isolated from the liver of patients with cirrhosis and fibrosis expressed CD90 and CD44 [33]. Moreover, a gene expression microarray confirmed that the expression level of CD90 ( THY1 ) was low, while the expression level of CD44 was very high (our unpublished data; see Table 1).…”
Section: Morphology and Phenotype Of Human Liver Mscssupporting
confidence: 49%
“…As with MSCs isolated from other sources, liver MSCs do not express markers of hematopoietic and endothelial cells, such as CD11b, CD14, CD19, CD31, CD34, CD45, CD79β, CD117, CD133, CD144, and HLA-DR [20,23,27,33,36]. The lack of expression of CD34, CD45, and CD117 on the surface of liver MSCs suggests that these cells are not so-called hepatic progenitor cells (the human counterpart to rodent oval cells) which are bipotent resident hepatic cells that can differentiate into hepatocytes and cholangiocytes [28,38].…”
Section: Morphology and Phenotype Of Human Liver Mscsmentioning
confidence: 99%
“…Several research groups using different differentiation protocols (Table 3) have demonstrated the ability of human liver MSCs to differentiate into hepatocyte-like cells in vitro [20,21,27,33,34,72,94]. The opposite was reported in just one paper by Porretti et al [92] claiming that cultured CD105 + CD73 + Thy-1 + CD45 − CD34 − MSCs obtained from the mononuclear fraction of the liver after removal of hepatocytes did not differentiate into the endothelial and hepatic lineages.…”
Section: Properties and Therapeutic Potential Of Human Liver Mscsmentioning
Chronic liver diseases constitute a significant economic, social, and biomedical burden. Among commonly adopted approaches, only organ transplantation can radically help patients with end-stage liver pathologies. Cell therapy with hepatocytes as a treatment for chronic liver disease has demonstrated promising results. However, quality human hepatocytes are in short supply. Stem/progenitor cells capable of differentiating into functionally active hepatocytes provide an attractive alternative approach to cell therapy for liver diseases, as well as to liver-tissue engineering, drug screening, and basic research. The application of methods generally used to isolate mesenchymal stem cells (MSCs) and maintain them in culture to human liver tissue provides cells, designated here as liver MSCs. They have much in common with MSCs from other tissues, but differ in two aspects—expression of a range of hepatocyte-specific genes and, possibly, inherent commitment to hepatogenic differentiation. The aim of this review is to analyze data regarding liver MSCs, probably another type of liver stem/progenitor cells different from hepatic stellate cells or so-called hepatic progenitor cells. The review presents an analysis of the phenotypic characteristics of liver MSCs, their differentiation and therapeutic potential, methods for isolating these cells from human liver, and discusses issues of their origin and heterogeneity. Human liver MSCs are a fascinating object of fundamental research with a potential for important practical applications.
“…The unique features of these cells include immunomodulatory properties and extensive regenerative potential. As shown by several research groups, the liver contains a pool of resident MSCs, which, in terms of their main characteristics (expression patterns of cell surface markers, adhesion, and morphology), correspond to those of MSCs isolated from other tissue sources [12][13][14]. Liver MSCs have several unique characteristics compared with those obtained from other tissue sources.…”
Liver diseases, characterized by high morbidity and mortality, represent a substantial medical problem globally. The current therapeutic approaches are mainly aimed at reducing symptoms and slowing down the progression of the diseases. Organ transplantation remains the only effective treatment method in cases of severe liver pathology. In this regard, the development of new effective approaches aimed at stimulating liver regeneration, both by activation of the organ’s own resources or by different therapeutic agents that trigger regeneration, does not cease to be relevant. To date, many systematic reviews and meta-analyses have been published confirming the effectiveness of mesenchymal stromal cell (MSC) transplantation in the treatment of liver diseases of various severities and etiologies. However, despite the successful use of MSCs in clinical practice and the promising therapeutic results in animal models of liver diseases, the mechanisms of their protective and regenerative action remain poorly understood. Specifically, data about the molecular agents produced by these cells and mediating their therapeutic action are fragmentary and often contradictory. Since MSCs or MSC-like cells are found in all tissues and organs, it is likely that many key intercellular interactions within the tissue niches are dependent on MSCs. In this context, it is essential to understand the mechanisms underlying communication between MSCs and differentiated parenchymal cells of each particular tissue. This is important both from the perspective of basic science and for the development of therapeutic approaches involving the modulation of the activity of resident MSCs. With regard to the liver, the research is concentrated on the intercommunication between MSCs and hepatocytes under normal conditions and during the development of the pathological process. The goals of this review were to identify the key factors mediating the crosstalk between MSCs and hepatocytes and determine the possible mechanisms of interaction of the two cell types under normal and stressful conditions. The analysis of the hepatocyte–MSC interaction showed that MSCs carry out chaperone-like functions, including the synthesis of the supportive extracellular matrix proteins; prevention of apoptosis, pyroptosis, and ferroptosis; support of regeneration; elimination of lipotoxicity and ER stress; promotion of antioxidant effects; and donation of mitochondria. The underlying mechanisms suggest very close interdependence, including even direct cytoplasm and organelle exchange.
Stromal liver cells obtained from liver biopsy specimens of a patient with alcoholic cirrhosis can proliferate for a long time in culture passing more than 30 passages. In the course of culturing from early to late passages, acceleration of cell proliferation, decrease of the expression of some markers, and loss of hepatogenic differentiation potential were observed. On passage 30, induced pluripotent stem cells were obtained from these cells and comparative analysis of adipogenic and hepatic differentiation potencies of these cells and original liver stromal cells was performed. Induced pluripotent stem cells differentiated into both directions more efficiently and more rapidly than initial cells. Under conditions of hepatic differentiation, liver stromal cells started to express markers of definitive endoderm, but not markers of immature/mature hepatocytes, whereas induced pluripotent stem cells consistently expressed markers of definitive endoderm, immature/mature hepatocytes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.