The Effects of Different Growth Factors on Human Bone Marrow Stromal Cells Differentiating into Hepatocyte-Like Cells

Abstract

Stem cells are self-renewable and are thought to be the pluripotent cells that can differentiate into a variety of cells or tissue types. For many years, adult stem cells harvested from bone marrow have been used therapeutically. In 1999, Pittenger et al. published the methods to induce differentiation of human mesenchymal stem cells into different cell types of mesodermal lineages. Theise et al. have demonstrated that hepatocytes, from endodermal lineage, can be derived from bone marrow in human and mice. Hepatocyte engraftment from bone marrow cells have been confirmed by double FISH (fluorescence in situ hybridization) after bone marrow transplantation. Lagasse et al. further demonstrated that purified hematopoietic stem cells from adult mouse bone marrow rescued fumarylacetoacetate hydrolase (FAH) deficient mice and restored the biochemical function of their liver. Alison et al.⁵showed that the human adult hematopoietic stem cell population is capable of yielding an epithelial lineage in chronically damaged liver. ß₂m^-/Thy-1⁺cells from rat and human bone marrow were integrated with hepatic cell plates and were differentiated into mature hepatocytes after intraportal infusion into rat livers studied by Avital et al.⁶ß_zm7Thy-1⁺cells also differentiated into mature hepatocytes in a culture system simulating liver regeneration and containing cholestatic serum. Oh et al.’ and Schwartz et al. have succeeded in differentiating rat bone marrow cells and multipotent adult progenitor cells from bone marrow into hepatocyte-like cells by addition of growth factors in the culture medium. Hamazaki et al. induced hepatic maturation in mouse embryonic stem cellsin vitro.Other studies suggest that the microenvironment of embryonic liver, including growth factors and cell-cell interactions, is critical for regulating liver development. Acidic FGF and HGF were known to play important roles in the early-and mid-developmental stages of liver development. So far, none have succeeded to induce human bone marrow stromal cells (BMSC) differentiation into hepatocytes in culture.