Simultaneous characterization of progenitor cell compartments in adult human liver

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Abstract

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)+/ CD49f +/CD29+/CD45-] accounted for 2.7-3.5% whereas hematopoietic (CD34+/ CD45+), endothelial [vascular endothelial growth factor-2 (KDR)+/CD146+/CD45 -], and mesenchymal [CD73+/CD105+/CD90 (Thy-1)+/CD45 -] 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.

Original languageEnglish
Pages (from-to)31-40
Number of pages10
JournalCytometry Part A
Volume77
Issue number1
DOIs
Publication statusPublished - Jan 2010

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Stem Cells
Liver
Liver Diseases
Integrin alpha6beta1
Flow Cytometry
Tissue Donors
Vascular Endothelial Growth Factor A
Digestion
Suspensions
Healthy Volunteers
Chronic Disease
Epithelium

Keywords

  • Flow cytometry
  • Human liver
  • Stem and progenitor cells

ASJC Scopus subject areas

  • Cell Biology
  • Histology
  • Pathology and Forensic Medicine

Cite this

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title = "Simultaneous characterization of progenitor cell compartments in adult human liver",
abstract = "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)+/ CD49f +/CD29+/CD45-] accounted for 2.7-3.5{\%} whereas hematopoietic (CD34+/ CD45+), endothelial [vascular endothelial growth factor-2 (KDR)+/CD146+/CD45 -], and mesenchymal [CD73+/CD105+/CD90 (Thy-1)+/CD45 -] 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.",
keywords = "Flow cytometry, Human liver, Stem and progenitor cells",
author = "Laura Porretti and Alessandra Cattaneo and Federico Colombo and Raffaella Lopa and Giorgio Rossi and Vincenzo Mazzaferro and Carlo Battiston and Gianluca Svegliati-Baroni and Francesco Bertolini and Paolo Rebulla and Daniele Prati",
year = "2010",
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doi = "10.1002/cyto.a.20834",
language = "English",
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pages = "31--40",
journal = "Cytometry. Part A : the journal of the International Society for Analytical Cytology",
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T1 - Simultaneous characterization of progenitor cell compartments in adult human liver

AU - Porretti, Laura

AU - Cattaneo, Alessandra

AU - Colombo, Federico

AU - Lopa, Raffaella

AU - Rossi, Giorgio

AU - Mazzaferro, Vincenzo

AU - Battiston, Carlo

AU - Svegliati-Baroni, Gianluca

AU - Bertolini, Francesco

AU - Rebulla, Paolo

AU - Prati, Daniele

PY - 2010/1

Y1 - 2010/1

N2 - 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)+/ CD49f +/CD29+/CD45-] accounted for 2.7-3.5% whereas hematopoietic (CD34+/ CD45+), endothelial [vascular endothelial growth factor-2 (KDR)+/CD146+/CD45 -], and mesenchymal [CD73+/CD105+/CD90 (Thy-1)+/CD45 -] 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.

AB - 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)+/ CD49f +/CD29+/CD45-] accounted for 2.7-3.5% whereas hematopoietic (CD34+/ CD45+), endothelial [vascular endothelial growth factor-2 (KDR)+/CD146+/CD45 -], and mesenchymal [CD73+/CD105+/CD90 (Thy-1)+/CD45 -] 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.

KW - Flow cytometry

KW - Human liver

KW - Stem and progenitor cells

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DO - 10.1002/cyto.a.20834

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SP - 31

EP - 40

JO - Cytometry. Part A : the journal of the International Society for Analytical Cytology

JF - Cytometry. Part A : the journal of the International Society for Analytical Cytology

SN - 1552-4922

IS - 1

ER -