TY - JOUR
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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U2 - 10.1002/cyto.a.20834
DO - 10.1002/cyto.a.20834
M3 - Article
C2 - 19960544
AN - SCOPUS:74049157708
VL - 77
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 -