Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver

Suzuki, Atsushi; Zheng, Yun‐Wen; Kondo, R; Kusakabe, Moriaki; Takada, Yasutsugu; Fukao, Katashi; Nakauchi, Hiromitsu; Taniguchi, Hideki

doi:10.1053/jhep.2000.20349

Cited by 277 publications

(263 citation statements)

References 41 publications

(51 reference statements)

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“…20 However, unlike oval cells, they do not express hepatocyte or cholangiocyte specific markers and c-kit. 21 Cells derived from a single H-CFU-C expand in vitro and are capable of reconstituting hepatocytic, bile-ductal, pancreatic and intestinal structures in vivo . 20 Whether H-CFU-C's exist in the adult liver has not been established; however, these cells may represent the resident hepatocyte progenitor.…”

Section: Oval Cell Originmentioning

confidence: 99%

Oval cell‐mediated liver regeneration: Role of cytokines and growth factors

Lowes

Croager

Olynyk

et al. 2002

J of Gastro and Hepatol

153

123

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In experimental models, which induce liver damage and simultaneously block hepatocyte proliferation, the recruitment of a hepatic progenitor cell population comprised of oval cells is invariably observed. There is a substantial body of evidence to suggest that oval cells are involved in liver regeneration, as they differentiate into hepatocytes and biliary cells. Recently, bone marrow cells were shown to be a source of a stem cells with the capacity to repopulate the liver. Presently, the relationship between bone marrow cells and oval cells is unclear. Investigations will be greatly assisted by the availability of in vitro models based on a knowledge of cytokines that affect oval cells. While the cytokines, which regulate the different hematopoietic lineages, are well characterized, there is relatively little information regarding those that influence oval cells. This review outlines recent developments in the field of oval cell research and focuses on cytokines and growth factors that have been implicated in regulating oval cell proliferation and differentiation.

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Section: Oval Cell Originmentioning

confidence: 99%

Oval cell‐mediated liver regeneration: Role of cytokines and growth factors

Lowes

Croager

Olynyk

et al. 2002

J of Gastro and Hepatol

153

123

View full text Add to dashboard Cite

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“…These signaling mechanisms may occur between stem cells, between support cells and stem cells, and between stem cells and differentiating cells. Cell/cell and cell/ECM adhesion and signaling in adult niches is mediated through cell adhesion receptors such as cadherins (Song et al, 2002;Zhang et al, 2003) and integrins (Jones and Watt, 1993;Shinohara et al, 1999;Suzuki et al, 2000;Fujimoto et al, 2002;Frye et al, 2003;Scott et al, 2003;Blanpain et al, 2004;Chen et al, 2004;Deb et al, 2004;Hidalgo et al, 2004;Corbel et al, 2005;Priestley et al, 2005;Wagers and Weissman, 2005;Bajanca et al, 2006;Pajoohesh-Ganji et al, 2006;Lawson et al, 2007;Yang et al, 2007). In this model, as a cell moves away from the niche and thus away from some regulatory signals, it adopts a differentiated phenotype as shown in the pair of cells to the right.…”

Section: Introductionmentioning

confidence: 99%

The microenvironment of the embryonic neural stem cell: Lessons from adult niches?

Lathia

Rao

Mattson

et al. 2007

Developmental Dynamics

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A better understanding of the signals regulating embryonic neural stem cells is clearly an important goal. However, many studies on neural stem cell biology are conducted on the slowly-dividing cells found in the adult CNS, where specialized microenvironments or niches maintain the stem cells throughout life. By contrast, the embryonic VZ is a transient structure that does not fulfill the criteria conventionally used to define niches. In this review we will examine whether, despite these differences, the signals found in other adult stem cell niches are present in the VZ. Using the similarities and differences we observe, we will reconsider whether the location of embryonic stem cell populations such as the VZ can be thought of as niches. Finally, we will ask how these lessons from the niche inform our understanding of neurodevelopmental diseases and cancers of the CNS. Developmental Dynamics 236:3267-3282, 2007.

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“…After evaluating a large panel of markers because no single antigen had been definitely validated (30), we observed that all of the cultured cells expressed the a6 and b1 integrins, fundamental in ensuring cell adhesion and clonality of hepatic progenitor cells (1,2). EpCAM and CD133 antigens were also expressed on freshly isolated L-EpPCs, but their reactivity progressively decreased as the cells matured, as also suggested by the gradual increase in CD166 and a1-antitrypsin positivity during culture.…”

Section: Discussionmentioning

confidence: 92%

“…Media were changed three times a week. LEnPCs and L-EpPCs were counted at each passage and, at the first and fifth passages, characterized for the expression of various markers (1,2,16,17,(19)(20)(21).…”

Section: In Vitro Cell Culturesmentioning

confidence: 99%

Simultaneous characterization of progenitor cell compartments in adult human liver

et al. 2009

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The human liver is a complex tissue consisting of epithelial, endothelial, hematopoietic, and mesenchymal elements that probably derive from multiple lineage-committed progenitors, but no comprehensive study aimed at identifying and characterizing intrahepatic precursors has yet been published. Cell suspensions for this study were obtained by enzymatic digestion of liver specimens taken from 20 patients with chronic liver disease and 13 multiorgan donors. Stem and progenitor cells were first isolated, amplified, and characterized ex vivo according to previously validated methods, and then optimized flow cytometry was used to assess their relative frequencies and characterize their immunophenotypes in the clinical specimens. Stem and progenitor cells committed to hematopoietic, endothelial, epithelial, and mesenchymal lineages were clearly identifiable in livers from both healthy and diseased subjects. Within the mononuclear liver cell compartment, epithelial progenitors [epithelial cell adhesion molecule (EpCAM) 1 / CD49f 1 /CD29 1 /CD45 2 ] accounted for 2.7-3.5% whereas hematopoietic (CD34 1 / CD45 1 ), endothelial [vascular endothelial growth factor-2 (KDR) 1 /CD146 1 /CD45 2 ], and mesenchymal [CD73 1 /CD105 1 /CD90 (Thy-1) 1 /CD45 2 ] stem cells and progenitors accounted for smaller fractions (0.02-0.6%). The patients' livers had higher percentages of hematopoietic and endothelial precursors than those of the donors. In conclusion, we identified and characterized precursors committed to four different lineages in adult human liver. We also optimized a flow cytometry approach that will be useful in exploring the contribution of these cells to the pathogenesis of liver disease. ' International Society for Advancement of CytometryKey terms stem and progenitor cells; human liver; flow cytometry ADULT human liver is a complex tissue consisting of epithelial, endothelial, hematopoietic, and mesenchymal elements. This supports the view that the intrahepatic stem and progenitor cell compartment probably consists of a heterogeneous pool with various molecular and functional markers. Studies characterizing hepatic stem cells and progenitors have so far mainly concentrated on the epithelial compartment, and generally used human fetal or rodent liver (1,2); only a few have identified and characterized the hematopoietic (3,4), endothelial (5), and mesenchymal lineages (6), although it is well known that their progenies are deeply involved in the pathogenesis of liver disease (7).Despite recent growth of interest in liver stem and progenitor cell research and great expectations concerning the potential of these cells in the field of regenerative medicine (8), we are unaware of comprehensive studies of the entire stem/progenitor cell pool. This could be due to the rare occurrence of these cells in liver tissue, and the possible overlap in the immunological profiles of the cells committed to different lineages (9-11), thus making their identification difficult.

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Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver

Cited by 277 publications

References 41 publications

Oval cell‐mediated liver regeneration: Role of cytokines and growth factors

Oval cell‐mediated liver regeneration: Role of cytokines and growth factors

The microenvironment of the embryonic neural stem cell: Lessons from adult niches?

Simultaneous characterization of progenitor cell compartments in adult human liver

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