Human hepatic stem cells from fetal and postnatal donors

“…: conception and design, financial support, data analysis and interpretation, manuscript writing, final approval of manuscript. expanded by limbal culture, differentiation potential of mesenchymal stromal cells from bone marrow, or the number and phenotype of pluripotent hepatic progenitors [13][14][15][16]. Although some of the observed discrepancies will undoubtedly be accounted for by tissue-specific differences [17], illdefined cell populations of origin and unreliable assays used for phenotypic readout have also contributed to blur the general picture [18].…”

Section: Introductionmentioning

confidence: 99%

Age-Dependent Depletion of Human Skin-Derived Progenitor Cells

Gago¹,

Pérez-López²,

Sanz-Jaka

et al. 2009

Stem Cells

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A major unanswered question in autologous cell therapy is the appropriate timing for cell isolation. Many of the putative target diseases arise with old age and previous evidence, mainly from animal models, suggests that the stem/progenitor cell pool decreases steadily with age. Studies with human cells have been generally hampered to date by poor sample availability. In recent years, several laboratories have reported on the existence, both in rodents and humans, of skin-derived precursor (SKP) cells with the capacity to generate neural and mesodermal progenies. This easily obtainable multipotent cell population has raised expectations for their potential use in cell therapy of neurodegeneration. However, we still lack a clear understanding of the spatiotemporal abundance and phenotype of human SKPs. Here we show an analysis of human SKP abundance and in vitro differentiation potential, by using SKPs isolated from four distinct anatomic sites (abdomen, breast, foreskin, and scalp) from 102 healthy subjects aged 8 months to 85 years. Human SKP abundance and differentiation potential decrease sharply with age, being extremely difficult to isolate, expand, and differentiate when obtained from the elderly. Our data suggest preserving human SKP cell banks early in life would be desirable for use in clinical protocols in the aging population.

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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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Human hepatic stem cells from fetal and postnatal donors

Cited by 533 publications

References 52 publications

The stem cell niche of human livers: Symmetry between development and regeneration

The stem cell niche of human livers: Symmetry between development and regeneration

Age-Dependent Depletion of Human Skin-Derived Progenitor Cells

Simultaneous characterization of progenitor cell compartments in adult human liver

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