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Interleukin-3 induces hepatocyte-specific metabolic activity in bone marrow-derived liver stem cells

Inderbitzin, Daniel ; Avital, Itzhak ; Keogh, Adrian ; Beldi, Guido ; Quarta, Mattia ; Gloor, Beat ; Candinas, Daniel

In: Journal of Gastrointestinal Surgery, 2005, vol. 9, no. 1, p. 69-74

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    Title
    • Interleukin-3 induces hepatocyte-specific metabolic activity in bone marrow-derived liver stem cells
    Author
    • Inderbitzin, Daniel. Department of Visceral and Transplant Surgery, University Hospital Bern, CH-3010, Bern, Switzerland
    • Avital, Itzhak. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
    • Keogh, Adrian. Department of Visceral and Transplant Surgery, University Hospital Bern, CH-3010, Bern, Switzerland
    • Beldi, Guido. Department of Visceral and Transplant Surgery, University Hospital Bern, CH-3010, Bern, Switzerland
    • Quarta, Mattia. Department of Visceral and Transplant Surgery, University Hospital Bern, CH-3010, Bern, Switzerland
    • Gloor, Beat. Department of Visceral and Transplant Surgery, University Hospital Bern, CH-3010, Bern, Switzerland
    • Candinas, Daniel. Department of Visceral and Transplant Surgery, University Hospital Bern, CH-3010, Bern, Switzerland
    Document Type
    • Postprint
    OAI-PMH Identifier
    • oai:doc.rero.ch:311521
    Summary
    Bone marrow-derived adult liver stem cells (BALSC) are a promising target for the development of future cell-based therapies for a variety of liver disorders. However, the ability of stem cells to fully function, as hepatocytes, is limited and differentiation is time dependent. Therefore, it will be conducive to find a growth factor that is able to enhance liver-specific metabolic activity in freshly isolated liver stem cells. Recently, a subpopulation of BALSC was isolated and characterized (β2-microglobulin-negative/ Thy-1-positive cells). We hypothesized that using interleukin-3 (IL-3), a hematopoietic differentiation growth factor, we may be able to enhance liver-specific metabolic activity in freshly isolated BALSC. Rat BALSC from normal and injured livers (bile duct ligated) were isolated and stimulated with IL-3 in culture. Cells were co-cultured with or without hepatocytes, separated by a semipermeable membrane. We measured the effect of IL-3 on BALSC to metabolize ammonia into urea (a liver-specific metabolic activity). IL-3 increased the ability of BALSC, purified from normal animals, to metabolize ammonia into urea by several folds. Interestingly, no such effect was found in cell cultures from bile ductligated animals. Additionally, co-cultures of BALSC with hepatocytes induced higher rate of ammonia metabolism, which was further enhanced by IL-3. Our study indicates that IL-3 may be used as an agent to enhance differentiation of BALSC, both qualitatively and quantitatively. It is conceivable that stem cells may undergo IL-3 priming before their clinical application in cell transplantation or bioartificial liver systems