Hepatic progenitor cells in human fetal liver express the oval cell marker Thy-1

Hepatic progenitor cells play a major role in regenerating diseased liver. In rodents, progenitors forming hepatocytes or cholangiocytes are identified by the stem cell marker Thy-1. The aim of this study was to ascertain whether progenitor cells expressing Thy-1 could be identified in human fetal liver. Midtrimester human fetal liver was immunostained for Thy-1, cytokeratins 18 and 19, vimentin, CD34, CD45, and fibrinogen. Thy-1+ and Thy-1+CD34+ populations were purified using fluorescence-activated cell sorting (FACS). Immunofluorescence and mRNA expression were used to examine the bipotential nature of purified stem cells. We found that Thy-1+ cells were concentrated in portal tracts but were also scattered in parenchyma. In FACS-prepared cells, 0.18–3.08% (median 0.65%, n = 14) of cells were Thy-1+. Immunophenotyping revealed that some Thy-1+ cells coexpressed cytokeratins 18 and 19, others, fibrinogen and cytokeratin 19. RT-PCR demonstrated that Thy-1+ cells expressed mRNA for Thy-1, cytokeratin 18, and cytokeratin 19, and Thy-1+CD34+ cells expressed mRNA for α-fetoprotein, transferrin, and hepatocyte nuclear factor-4α. Thy-1+ cells were identified in fetal liver. These cells expressed several lineage markers, including coexpression of biliary and hepatocellular proteins and mRNA. These data suggest that Thy-1 is a marker of liver stem cells in human fetal liver.

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Promoter-defined isolation and identification of hepatic progenitor cells from the human fetal liver

Histochemistry and Cell Biology ◽

10.1007/s00418-008-0439-2 ◽

2008 ◽

Vol 130 (2) ◽

pp. 375-385 ◽

Cited By ~ 8

Author(s):

Ping Wang ◽

Haiyan Zhang ◽

Weihong Li ◽

Yongmei Zhao ◽

Wei An

Keyword(s):

Progenitor Cells ◽

Fetal Liver ◽

Hepatic Progenitor Cells ◽

Isolation And Identification ◽

Human Fetal Liver

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OR19-02 Luteinizing Hormone/Human Chorionic Gonadotropin Receptor Protein Expression in Adrenocortical Progenitor Cells, Aldosterone Producing Cell Clusters and Adrenal Adenomas Derived from Postmenopausal Women

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1076 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Effie Tsomos ◽

Regina Belokovskaya ◽

Jose Sanchez Escobar ◽

Shen Yao ◽

Kazutaka Nanba ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Postmenopausal Women ◽

Progenitor Cells ◽

Stem Cell Marker ◽

Cell Marker ◽

Immunohistochemical Expression ◽

Cell Clusters ◽

Blinded Fashion ◽

Archival Specimens

Abstract Objective/Background Adrenal pathologies are more common in women than men. Embryologically the adrenals and gonads develop from the adrenogenital ridge with differential migration and differentiation. We hypothesized that in adult females there are adrenocortical progenitor cells that express the LH/hCG-R and proliferate in response to elevated LH. Indeed, several case reports demonstrated LH/hCG-R expression in adrenal secretory tumors in postmenopausal and pregnant females. In aging adults, nests of cells known as aldosterone-producing cell clusters (APCCs) that may be precursors to aldosterone producing adenomas are frequently detected. We retrospectively studied the immunohistochemical expression of LH/hCG-R in normal adrenals, adrenal adenomas and APCCs in archival specimens derived from post-menopausal women. Methods Archival specimens from adrenal adenomas derived from 23 women >55 years of age were examined. Clinical data was obtained in a blinded fashion and hormonal data was available in 9/23 cases; 6/9 were secreting cortisol and 3/9 adenomas were secreting aldosterone. In addition, 6 samples derived from a repository of normal adrenal tissues from deceased kidney donors (1 male, and 5 postmenopausal females) were studied. All specimens were immunostained for LH/hCG-R and the adrenal stem cell marker DLK1 that facilitates the maintenance of an undifferentiated phenotype. The normal adrenal tissues were also stained for aldosterone synthase (CYP11B2) to detect APCCs. The slides were reviewed and graded by a pathologist in a blinded fashion. Results Expression of LH/hCG-R was demonstrated in both normal and adenomatous tissues in all 23 specimens. The staining in adenomas was heterogeneous, with clusters of densely stained LH/hCG-R positive cells in all specimens. There were less densely stained clusters in normal adjacent adrenocortical tissue that was most prominent in the subcapsular, zona glomerulosa region, an area where the putative adrenal cortical stem cells are found as well as the zona reticularis. Double staining for the stem cell marker DLK1 and LH/hCG-R confirmed that these cells represent adrenocortical progenitor cells. CYP 11B2 immunohistochemistry of normal adrenals demonstrated cell foci dipping from the capsule into the zona fasciculata classified as APCCs that co-expressed cytoplasmic LH/hCGR. Conclusion Adrenal adenomas and APCCs derived from postmenopausal women exhibited heterogeneous but strong immunohistochemical expression of LH/hCG-R in all samples. Interestingly, DLK1-positive adrenocortical stem cells in the subcapsular zone also expressed LH/hCG-R. These data may provide insights into the female predominance of adrenal pathologies, particularly in postmenopausal women with high LH levels. The LH/hCG-R may be a viable target for treatment of adrenal adenomas in postmenopausal women.

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Faculty Opinions recommendation of Isolation of multipotent progenitor cells from human fetal liver capable of differentiating into liver and mesenchymal lineages.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.723933849.793541287 ◽

2018 ◽

Author(s):

Piotr Czauderna

Keyword(s):

Progenitor Cells ◽

Fetal Liver ◽

Human Fetal Liver ◽

Multipotent Progenitor Cells

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Use of human fetal liver cells for treatment of patients with lower limb peripheral artery disease

Cell and Organ Transplantology ◽

10.22494/cot.v2i1.39 ◽

2014 ◽

Vol 2 (1) ◽

pp. 10-13

Author(s):

R. Salyutin ◽

D. Dombrowski ◽

M. Komarov ◽

N. Sokolov ◽

S. Palyanitsya ◽

...

Keyword(s):

Progenitor Cells ◽

Lower Limb ◽

Fetal Liver ◽

Life Quality ◽

Liver Cells ◽

Surgical Reconstruction ◽

Clinical Effects ◽

Doppler Flowmetry ◽

Human Fetal Liver ◽

Fetal Liver Cells

In the group of patients (n = 21, mean age 54 ± 5.8 years) with chronic lower limb ischemia stage IIB who were non-liable for reconstructiverestoration surgery, we have established positive clinical effects of local transplantation of human fetal liver progenitor cells. Complex examination following 1, 3, 6 and 12 months after transplantation included duplex scanning of limb arteries, x-ray contrast arteriography and laser Doppler flowmetry as well as measuring pain-free walking and evaluating life quality based on individual questionnaire data.Owing to the transplant “Cryopreserved human fetal liver progenitor cells” the patients demonstrated stable increase of life quality index and pain-free walking as well as improvement of general health allowing assign them to the group of patients with lower ischemia stage, quicker social rehabilitation and lesser risk of disabling surgery (р < 0.05). Also, there were observations of improved microcirculation in the ischemic extremities owing to activation of endothelium-independent mechanisms of vasodilatation, reduced myotonus and neurotonus of the pre-capillaries and improved endothelium-dependent influence on the microhaemodynamic and, hence, an increased reserve capillary blood flow (p < 0.05).Analysis of the obtained results indicates prospects and effectiveness of using fetal liver cells transplantation in the patients who are not liable for surgical reconstruction of the vascular bed.

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Hepatitis C virus infection induces endoplasmic reticulum stress and apoptosis in human fetal liver stem cells

The Journal of Pathology ◽

10.1002/path.5240 ◽

2019 ◽

Vol 248 (2) ◽

pp. 155-163 ◽

Cited By ~ 1

Author(s):

Xuan Guo ◽

Wei‐Li Liu ◽

Dong Yang ◽

Zhi‐Qiang Shen ◽

Zhi‐Gang Qiu ◽

...

Keyword(s):

Stem Cells ◽

Endoplasmic Reticulum ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Virus Infection ◽

Endoplasmic Reticulum Stress ◽

Fetal Liver ◽

Hepatitis C Virus Infection ◽

Human Fetal Liver ◽

Liver Stem Cells

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Identification of human chronic myelogenous leukemia progenitor cells with hemangioblastic characteristics

Blood ◽

10.1182/blood-2004-07-2514 ◽

2005 ◽

Vol 105 (7) ◽

pp. 2733-2740 ◽

Cited By ~ 59

Author(s):

Baijun Fang ◽

Chunmei Zheng ◽

Lianming Liao ◽

Qin Han ◽

Zhao Sun ◽

...

Keyword(s):

Stem Cells ◽

Endothelial Cells ◽

Progenitor Cells ◽

Chronic Myelogenous Leukemia ◽

Blood Cells ◽

Fusion Gene ◽

Fetal Liver ◽

Philadelphia Chromosome ◽

Myelogenous Leukemia ◽

Leukemic Cells

AbstractOverwhelming evidence from leukemia research has shown that the clonal population of neoplastic cells exhibits marked heterogeneity with respect to proliferation and differentiation. There are rare stem cells within the leukemic population that possess extensive proliferation and self-renewal capacity not found in the majority of the leukemic cells. These leukemic stem cells are necessary and sufficient to maintain the leukemia. Interestingly, the BCR/ABL fusion gene, which is present in chronic myelogenous leukemia (CML), was also detected in the endothelial cells of patients with CML, suggesting that CML might originate from hemangioblastic progenitor cells that can give rise to both blood cells and endothelial cells. Here we isolated fetal liver kinase-1–positive (Flk1+) cells carrying the BCR/ABL fusion gene from the bone marrow of 17 Philadelphia chromosome–positive (Ph+) patients with CML and found that these cells could differentiate into malignant blood cells and phenotypically defined endothelial cells at the single-cell level. These findings provide direct evidence for the first time that rearrangement of the BCR/ABL gene might happen at or even before the level of hemangioblastic progenitor cells, thus resulting in detection of the BCR/ABL fusion gene in both blood and endothelial cells.

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