Are bone marrow mononuclear cells effective in reducing hepatic lesions?
Liver fibrosis occurs in the setting of chronic injury caused by different etiologies constituting a serious worldwide public health problem. In addition to schistosomiasis, hepatopathies due to alcohol, viral hepatitis, drugs, metabolic and autoimmune diseases, and congenital abnormalities are important causes of liver fibrosis. New therapeutic strategies aiming to minimize damages caused by hepatic fibrogenesis in chronic liver diseases are of great interest. Adult bone marrow contains pluripotent stem cells with the ability to differentiate into diverse cell types, including hepatocytes. The regenerative potential of bone marrow stem cells has been tested in experimental models of hepatic injury, demonstrating the ability of bone marrow cells (BMCs) to generate hepatocytes under tissue stress in mice and human. A research team leaded by Milena Botelho Pereira Soares from Brazil investigated the potential of syngeneic bone marrow mononuclear cells in the modulation of fibrosis, albumin expression and cellular alterations. This will be published on October 14, 2008 in the World Journal of Gastroenterology
They found that Transplanted GFP+ cells migrated to granuloma areas and reduced the percentage of liver fibrosis. The presence of donor-derived cells was confirmed by Fluorescence in situ hybridization (FISH) analysis for detection of cells bearing Y chromosome and by PCR analysis for detection of GFP DNA. The levels of TGF-beta, a cytokine associated with fibrosis deposition, in liver fragments of mice submitted to therapy were reduced. The number of oval cells in liver sections of S.mansoni -infected mice increased 3-4 fold after transplantation. A partial recovery in albumin expression, which is decreased upon infection with S.mansoni, was found in livers of infected mice after cellular therapy.
They concluded that transplantation of BMCs in mice with chronic liver disease caused by S.mansoni infection decreased liver fibrosis and contributed to an increase in precursor cells as well as to the generation of new hepatocytes and/or to the improvement of the function of resident hepatocytes. Although there are still many unanswered questions regarding the mechanisms of action of transplanted cells in hepatic lesions, their results reinforce the use of cell-based therapies for patients with chronic liver diseases