Background/Aims
Recent studies indicate that after transplantation, circulating bone marrow-derived
stem cells migrate into the liver and contribute to liver regeneration. Whether such
cells are actively recruited from the bone marrow for liver repair remains to be determined.
In this regard, we investigated whether liver resection leads to a release of stem
cell marker-positive (+) cells into the peripheral circulation.
Methods
Peripheral blood samples from 11 living liver donors were analyzed by flow cytometry
one day before and 12 h after partial hepatectomy (PH) using antibodies against CD133, CD34, CD45, CD14,
c-kit, bcrp-1. Immunomagnetic separation was performed to select CD133+ cells for functional assays in vitro.
Results
A significant increase in the percentage of CD133+ cells could be demonstrated in all donors studied. Unexpectedly, virtually all CD133+ cells coexpressed CD45 and CD14, whereas only a small subset expressed CD34. No significant
staining was observed for c-kit and bcrp-1. In culture, immunoselected CD133+ cells displayed characteristics of myelomonocytic precursors. In addition, enriched
CD133+ generated an adherent cell population that expressed CK8, alpha-fetoprotein, and
human albumin.
Conclusions
PH induces mobilization of a distinct population of myelomonocytic progenitor cells,
which have hepatic differentiation potential in vitro, and might play a role in liver
regeneration after PH in humans.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of HepatologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Heterogeneity and plasticity of hepatocyte lineages cells.Hepatology. 2001; 33: 738-750
- Bone marrow to liver: the blood of Prometheus.Semin Cell Dev Biol. 2002; 13: 411-417
- Liver regeneration after hepatectomy.Hepatogastroenterology. 2001; 48: 556-562
- Liver regeneration following hepatic injury.in: Strain A. Diehl A.M. Liver growth and repair. Chapman and Hall, London1998
- Liver regeneration.J Hepatol. 2000; 32: 19-31
- Liver regeneration.Science. 1997; 276: 60-66
- Liver stem cells.in: Potten C.S. Stem cells. Academic Press, London1997
- Epithelial-like stem cells of the rodent liver.in: Strain A. Diehl A.M. Liver growth and repair. Chapman and Hall, London1998
- Hepatic stem cells.Pathology. 2001; 33: 130-141
- Identificationof bipotential progenitor cells in normal and injured livers.Hepatology. 1996; 23: 476-481
- Mouse A6-positive hepatic oval cells also express several hematopoietic stem cell markers.Hepatology. 2003; 37: 632-640
- Bone marrow as a potential source of hepatic oval cells.Science. 1999; 284: 1168-1170
- Liver from bone marrow in humans.Hepatology. 2000; 32: 11-16
- Albumin expressing hepatocyte-like cells develop in the livers of immune deficient mice transplanted with highly purified human hematopoietic stem cells.Blood. 2003; 101: 4201-4208
- Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation.Hepatology. 2000; 31: 235-240
- Hepatocytes from non-hepatic adult stem cells.Nature. 2000; 406: 257
- Purified hematopoietic stem cells can differentiate into hepatocytes in vivo.Nat Med. 2000; 6: 1212-1213
- Cusella-De Angelis G.Coletta M, Paolucci E, Stornaiuolo A. Muscle regeneration by bone marrow-derived myogenic progenitors. Science. 1998; 279: 1528-1530
- Bone marrow cells regenerate infarcted myocardium.Nature. 2001; 410: 701-705
- Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice.Proc Natl Acad Sci USA. 1997; 94: 4080-4085
- Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell.Cell. 2001; 105: 369-377
- Pluripotency of mesenchymal stem cells derived from adult marrow.Nature. 2002; 418: 41-49
- Myelomonocytic cells are sufficient for therapeutic cell fusion in liver.Nat Med. 2004; 10: 744-748
- Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation.Nat Med. 2004; 10: 494-501
- Hematopoietic myelomonocytic cells are the major source of hepatocyte fusion partners.J Clin Invest. 2004; 113: 1266-1270
- Cell fusion is the principal source of bone-marrow-derived hepatocytes.Nature. 2003; 422: 897-901
- Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates.Nat Med. 2003; 9: 1520-1527
- Transplanted bone marrow regenerates liver by cell fusion.Nature. 2003; 422: 901-904
- Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes.Nature. 2003; 425: 968-973
- CD34: structure, biology, and clinical utility.Blood. 1996; 87: 1-13
- Isolation of putative progenitor endothelial cells for angiogenesis.Science. 1997; 275: 964-967
- Expression of the CD34 gene in vascular endothelial cells.Blood. 1990; 75: 2417-2426
- AC133, a novel marker for human hematopoietic stem and progenitor cells.Blood. 1997; 90: 5002-5012
- A novel five-transmembrane hematopoietic stem cell antigen: Isolation, characterization, and molecular cloning.Blood. 1997; 90: 5012-5013
- In vitro differentiation of endothelial cells from AC133-positive progenitors.Blood. 2000; 95: 3106-3112
- Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors.Blood. 2000; 95: 952-958
- AC133-2, a novel isoform of human AC133 stem cell antigen.J Biol Chem. 2002; 277: 20711-20716
- The biology and clinical uses of blood stem cells.Blood. 1997; 89: 2233-2258
- HGF, SDF-1, and MMP-9 are involved in stress-induced human CD34+ stem cell recruitment to the liver.J Clin Invest. 2003; 112: 160-169
- Reevaluation of bone marrow-derived cells as a source for hepatocyte regeneration.Cell Transplant. 2004; 13: 659-666
- Bone marrow progenitors are not the source of expanding oval cells in injured liver.Stem Cells. 2004; 22: 1049-1061
- Contribution of bone marrow cells to liver regeneration after partial hepatectomy in mice.J Hepatol. 2002; 36: 653-659
- Detection of recipient's cells in liver graft using antibodies to mismatched HLA class I antigens.Liver Transpl. 2004; 10: 1014-1406
- Hematopoietic stem cells convert into liver cells within days without fusion.Nat Cell Biol. 2004; 6: 532-539
- A human peripheral blood monocyte-derived subset acts as pluripotent stem cells.Proc Natl Acad Sci. 2003; 100: 2426-2431
- Bone marrow monocyte lineage cells adhere on injured endothelium in a monocyte chemoattractant protein-1-dependent manner and accelerate reendothelialization as endothelial progenitor cells.Circ Res. 2003; 93: 980-989
Article info
Publication history
Published online: June 28, 2005
Accepted:
May 2,
2005
Received in revised form:
April 20,
2005
Received:
August 5,
2004
See Editorial, pages 754–756Identification
Copyright
© 2005 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
