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

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 (beta2-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 duct-ligated 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.