Expression of the stem cell factor receptor c-kit in normal and diseased pediatric liver: Identification of a human hepatic progenitor cell?

Baumann, Ulrich; Crosby, Heather A.; Ramani, Pramila; Kelly, Déirdre; Strain, Alastair J.

doi:10.1002/hep.510300140

Cited by 167 publications

(129 citation statements)

References 32 publications

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“…The presence of oval cells in human liver has been reported, these cells proliferated in the periportal region and were suggested to be derived from a stem cell compartment (De Vos and Desmet, 1992;Haque et al, 1996;Demetris et al, 1996;Roskams et al, 1996;Ruck et al, 1996). The largest number of stem cells was observed in the periportal region in fulminant hepatic failure (Baumann et al, 1999). The hTERT-positive hepatocytes we reported here were mostly found at or around the periportal region, and they might be candidates for dormant stem (oval) cells.…”

Section: Discussionmentioning

confidence: 97%

Immuno-histochemical detection of human telomerase reverse transcriptase in human liver tissues

et al. 2000

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Although telomerase activity in hepatocellular carcinoma (HCC) increases in accordance with degree of histological undi erentiation, it is unknown whether the level of telomerase activity in HCC re¯ects of the degree of activity in individual cells or the frequency of telomerasepositive HCC cells. Non-cancerous liver tissues exhibit low but signi®cant levels of telomerase activity, but the nature of telomerase-positive cells in these tissues is unclear. In this study, we performed immunohistochemical staining using speci®c antibody against telomerase reverse transcriptase (hTERT) protein in 15 HCC samples and 13 adjacent non-cancerous liver tissues. There were hTERT-positive hepatocytes, though very low frequency, in non-cancerous liver tissues. The frequencies in hTERT positive hepatocytes were very well correlated with clinicopathological parameters and telomerase activity levels: the average frequencies of chronic hepatitis was 0.2%, liver cirrhosis 0.2%, welldi erentiated HCC 3.0%, moderately di erentiated HCC 28%, and poorly di erentiated HCC 95%. The intensity of staining varied among cells within a given specimen, and correlation with degree of histological undi erentiation was less obvious. Portions of migrating lymphocytes and biliary epithelial cells were also hTERT-positive. These ®ndings indicate that the upregulation of telomerase activity with degree of undi erentiation of HCC is mainly due to the increase in frequency of hTERT positive HCC cells. Oncogene (2000) 19, 3888 ± 3893.

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Section: Discussionmentioning

confidence: 97%

Immuno-histochemical detection of human telomerase reverse transcriptase in human liver tissues

et al. 2000

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“…The presence of a facultative liver stem cell compartment has been documented in both animals [4][5][6][7][8] and humans. 14,16,21,22 However, the exact anatomic location of these cells has been difficult to ascertain. The presence of blast-like cells in the bile ducts of rats treated with carcinogens has been clearly documented.…”

Section: Discussionmentioning

confidence: 99%

Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation

et al. 2000

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Following a report of skeletal muscle regeneration from bone marrow cells, we investigated whether hepatocytes could also derive in vivo from bone marrow cells. A cohort of lethally irradiated B6D2F1 female mice received whole bone marrow transplants from age-matched male donors and were sacrificed at days 1, 3, 5, and 7 and months 2, 4, and 6 posttransplantation (n ‫؍‬ 3 for each time point).

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“…33 Similar findings have also been observed for cholangiocytes, in which cells exhibiting the oval-cell phenotype were only integrated into the bile ducts of cirrhotic livers. [34][35][36] Accordingly, chimerism on the cholangiocyte level might be set off quite early after transplantation by elevated cell turnover as it regularly occurs in cholangitis during acute rejection. 37 This could help explain the remarkably high degree of cholangiocyte chimerism observed in this study.…”

Section: Discussionmentioning

confidence: 99%

High frequency of epithelial chimerism in liver transplants demonstrated by microdissection and STR-analysis

Kleeberger¹,

Rothämel²,

Glöckner³

et al. 2002

Hepatology

105

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It has recently been shown that epithelial cells derived from stem cells originating outside the liver are integrated into liver allografts. Whether epithelial intragraft chimerism protects transplants from rejection or chronic transplant dysfunction, and whether it interferes with recurrence of primary liver disease, is not known. Twenty-seven sequential biopsies derived from 9 liver-transplant recipients were studied for chimerism of hepatocytes and cholangiocytes. The target cells were isolated by laser microdissection after cytokeratin immunolabeling and genotyped using DNA analysis of a highly polymorphic short tandem repeat. Irrespective of whether early (up to 4 weeks) or late (more than 12 months) posttransplantation biopsies were studied, cholangiocyte chimerism was almost constantly found in 91% of the samples. No significant differences occurred between samples derived from patients with chronic organ dysfunction (n ‫؍‬ 3), recurrent hepatitis (n ‫؍‬ 3), or mild, unspecific changes (n ‫؍‬ 3). By contrast, hepatocyte chimerism tended to occur later (55% vs. 22%) and appeared to be associated with recurrent hepatitis (67% vs. 27%). In this respect, chronic organ dysfunction did not differ from mild, unspecific changes. While cholangiocyte chimerism represents a constant and early phenomenon in liver transplantations, an enhanced chimeric integration of recipient-derived hepatocytes can be observed in recurrent hepatitis, supporting the concept of an increased recruitment of extrahepatic progenitor cells to the liver in chronic hepatitis. (HEPATOLOGY 2002;35:110-116.)

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Expression of the stem cell factor receptor c-kit in normal and diseased pediatric liver: Identification of a human hepatic progenitor cell?

Cited by 167 publications

References 32 publications

Immuno-histochemical detection of human telomerase reverse transcriptase in human liver tissues

Immuno-histochemical detection of human telomerase reverse transcriptase in human liver tissues

Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation

High frequency of epithelial chimerism in liver transplants demonstrated by microdissection and STR-analysis

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