Identification of adult hepatic progenitor cells capable of repopulating injured rat liver

Yovchev, Mladen I.; Grozdanov, Petar; Zhou, Haoran; Racherla, Harini; Guha, Chandan; Dabeva, Mariana D.

doi:10.1002/hep.22047

Cited by 223 publications

(220 citation statements)

References 34 publications

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“…We noted that EpC can associate with cld-7 (14,34). Notably, EpC and cld-7 also display striking colocalization in hepatic progenitor cells with repopulating capacity (40). Colocalization in tumor cells and progenitor cells suggests that this association may have a major effect on EpC-mediated functions.…”

Section: Discussionmentioning

confidence: 71%

“…7A and B). The HEK-EpC-cld-7 and HEK-cld-7 tumor -bearing mice developed a single, solid intraperitoneal Several clinical studies report on convincing therapeutic efficacy of EpC-specific antibodies, particularly with respect to a reduction in ascitic load (35,(39)(40)(41)(42)(43)(44). Hence, we finally asked whether coexpression of cld-7 alters the growth profile of EpC-expressing tumor cells and whether the therapeutic efficacy of EpC-specific antibodies correlates with the EpCcld-7 association.…”

Section: Mol Cancer Res 2009;7(3) March 2009mentioning

confidence: 99%

“…Whereas in the peritoneal cavity, macrophages are recruited that obviously contribute to tumor cell damage, the EpC-cld-7 -expressing tumor cells may have a growth advantage after settlement in the thymus, as was suggested for early thymocyte progenitors, which also express EpC (51)(52)(53). As markers of hepatic progenitor cells with repopulating capacity (40), the EpC-cld-7 complex might also promote stem cell/cancer-initiating cell communication with niche elements. This hypothesis remains to be consolidated.…”

Section: The Tumor Growth -Promoting Features Of Epc Rely On the Assomentioning

confidence: 99%

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Claudin-7 Regulates EpCAM-Mediated Functions in Tumor Progression

Nübel¹,

Preobraschenski²,

Tuncay³

et al. 2009

Molecular Cancer Research

104

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EpCAM has been described as a therapeutically relevant tumor marker. We noted an interaction between EpCAM and the tight junction protein claudin-7 and here explored the nature of this interaction and its effect on EpCAM-mediated functions. The interaction between EpCAM and claudin-7 was defined in HEK293 cells transfected with rat claudin-7 and EpCAM cDNA. Deletions of the epidermal growth factor -like and the thyroglobin repeat domains of EpCAM or the cytoplasmic domain of EpCAM or claudin-7 did not prevent the EpCAM-claudin-7 association. A chimeric EpCAM molecule with an exchange of the cytoplasmic and transmembrane domains and an EpCAM molecule with point mutations in an AxxxG motif in the transmembrane region do not associate with claudin-7. HEK cells and the rat pancreatic tumor line BSp73AS, transfected with (mutated) EpCAM and claudin-7 cDNA, revealed that the association of both molecules severely alters the functional activity of EpCAM. Claudin-7 -associated

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Section: Discussionmentioning

confidence: 71%

Section: Mol Cancer Res 2009;7(3) March 2009mentioning

confidence: 99%

Section: The Tumor Growth -Promoting Features Of Epc Rely On the Assomentioning

confidence: 99%

See 1 more Smart Citation

Claudin-7 Regulates EpCAM-Mediated Functions in Tumor Progression

Nübel¹,

Preobraschenski²,

Tuncay³

et al. 2009

Molecular Cancer Research

104

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“…2, panel C). Moreover, freshly isolated L-EpPCs expressed epithelial cell adhesion molecule (EpCAM) and CD133-1, which have recently been identified as markers of hepatic progenitor cells (20,21,23), but this expression progressively decreased in culture, whereas the expression of neural cell adhesion molecule (NCAM) and CD166 antigens increased during the five culture passages (Fig. 2, panel C).…”

Section: L-eppcsmentioning

confidence: 95%

“…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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