Liver‐Specific Gene Expression in Cultured Human Hematopoietic Stem Cells

Hematopoietic and hepatic stem cells share characteristic markers such as CD34, c‐kit, and Thy1. Based on the recent observations that hepatocytes may originate from bone marrow, we investigated the potential of CD34+ bone marrow cells to differentiate into hepatocytic cells in vitro. CD34+ and CD34− human bone marrow cells were separated by magnetic cell sorting. Cells were cultured on a collagen matrix in a defined medium containing hepatocyte growth factor. Cell count and size were measured by flow cytometry, and reverse transcription polymerase chain reaction was carried out for the liver‐specific markers CK‐19 and albumin. During cell culture, CD34+ cells showed an increasing cell number and proliferative activity as assessed by Ki‐67 staining. Under the specified culture conditions, CD34+ cells expressed albumin RNA and CK‐19 RNA after 28 days, whereas CD34− cells did not show liver‐specific gene expression. The results indicate that CD34+ adult human bone marrow stem cells can differentiate into hepatocytic cells in vitro.

[1]  M. Grompe Liver repopulation for the treatment of metabolic diseases , 2001, Journal of Inherited Metabolic Disease.

[2]  G. Feldmann Liver transplantation of hepatic stem cells: potential use for treating liver diseases , 2004, Cell Biology and Toxicology.

[3]  E. Scott,et al.  Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization , 2002, Nature Medicine.

[4]  R. Schwartz,et al.  Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. , 2002, The Journal of clinical investigation.

[5]  A. Ruifrok,et al.  Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells. , 2002, The New England journal of medicine.

[6]  Neil D. Theise,et al.  Multi-Organ, Multi-Lineage Engraftment by a Single Bone Marrow-Derived Stem Cell , 2001, Cell.

[7]  D. Kelly,et al.  Human hepatic stem-like cells isolated using c-kit or CD34 can differentiate into biliary epithelium. , 2001, Gastroenterology.

[8]  H. Malhi,et al.  Hepatocyte transplantation: new horizons and challenges. , 2001, Journal of hepato-biliary-pancreatic surgery.

[9]  C. Guha,et al.  Hepatocyte-based gene therapy. , 2001, Journal of hepato-biliary-pancreatic surgery.

[10]  E. Keeffe,et al.  Liver transplantation: current status and novel approaches to liver replacement. , 2001, Gastroenterology.

[11]  C. Vessey,et al.  HEPATIC STEM CELLS: A REVIEW , 2001, Pathology.

[12]  M. Sakaguchi,et al.  Hepatocyte growth factor induces differentiation of adult rat bone marrow cells into a hepatocyte lineage in vitro. , 2000, Biochemical and biophysical research communications.

[13]  S. Mckercher,et al.  Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. , 2000, Science.

[14]  Xin Wang,et al.  Purified hematopoietic stem cells can differentiate into hepatocytes in vivo , 2000, Nature Medicine.

[15]  Rebekah Gardner,et al.  Liver from bone marrow in humans , 2000, Hepatology.

[16]  J. Vacanti,et al.  Alternatives to liver transplantation: from hepatocyte transplantation to tissue-engineered organs. , 2000, Gastroenterology.

[17]  Sunil Badve,et al.  Derivation of hepatocytes from bone marrow cells in mice after radiation‐induced myeloablation , 2000, Hepatology.

[18]  W. Mars,et al.  Bone marrow as a potential source of hepatic oval cells. , 1999, Science.

[19]  N. Fausto,et al.  Generation of hepatocytes from oval cell precursors in culture. , 1998, Cancer research.

[20]  S. Rafii,et al.  Evidence for circulating bone marrow-derived endothelial cells. , 1998, Blood.

[21]  G Cossu,et al.  Muscle regeneration by bone marrow-derived myogenic progenitors. , 1998, Science.

[22]  M. Grompe,et al.  Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes. , 1997, The American journal of pathology.

[23]  É. Mezey,et al.  Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[24]  D. Prockop Marrow Stromal Cells as Stem Cells for Nonhematopoietic Tissues , 1997, Science.

[25]  Steven E. Wilson,et al.  Expression of HGF, Its Receptor c-met, c-myc, and Albumin in Cirrhotic and Neoplastic Human Liver Tissue , 1997, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[26]  J. Stockert,et al.  A New Fluorescence Reaction in DNA Cytochemistry: Microscopic and Spectroscopic Studies on the Aromatic Diamidino Compound M&B 938 , 1997, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[27]  S. Thorgeirsson Hepatic stem cells in liver regeneration , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[28]  P. Stasiak,et al.  Sequence of cDNA coding for human keratin 19. , 1987, Nucleic acids research.

[29]  S. Thorgeirsson,et al.  A precursor-product relationship exists between oval cells and hepatocytes in rat liver. , 1987, Carcinogenesis.

[30]  R. Nuscher,et al.  Bone marrow transplantation. , 1977, The American journal of nursing.