New Delhi, India -
There are numerous reports in the literature of bone marrow cells "transdifferentiating" into hepatocytes, or alternatively, bone marrow cells having hepatic precursors that can differentiate into hepatocytes.
The possibility of this occuring is substantiated by studies in sex mismatch clinical bone marrow transplant recipients in which liver biopsies from the recipient reveals expression of bone marrow derived cells making up hepatocytes.
In a recent study (Khurana et al. Characterization of the potential subpopulation of bone marrow cells involved in the repair of injured liver tissue.Stem Cells. 2007 Mar 22) it was demonstrated that subsequent to induction of liver injury using carbon tetrachloride bone marrow Lin(-)Sca-1(+) cells begin to increase proliferation and enter systemic circulation. It was demonstrated that these cells can differentiate into hepatocyte-like cells which express both albumin and cytokeratin-18. This was also demonstrated with labelled bone marrow cells. Interestingly, the differentation of the bone marrow cells into hepatic-like cells was associated with very little fusion, as identified using quantitative PCR analysis for recipient specific gene (sry).
This study should come as no surprise since others have reported that administration of autologous bone marrow cells into patients with liver failure causes a positive clinical effect.
Specifically, Terai et al (Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells. 2006 Oct;24(10):2292-8.) treated 9 patients with autologous bone marrow (400 ml total extracted, total mononuclear cells infused were about 5 billion). Improvements were observed in serum albumin, Child-Pugh score, alpha-fetoprotein, and overall plasma protein after systemic infusion of stem cells. All improvements reached statistical significance
In another study, Lyra et al (Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease. World J Gastroenterol. 2007 Feb 21;13(7):1067-73) used only 50 ml of autologous bone marrow aspirate to treat 10 patients with liver failure. In contrast to the previous study, Lyra et al injected the cells into the hepatic artery using the same technique utilized for transcatheter chemoembolization. It was reported that statistically significant increases in serum albumin, as well as decreased bilirubin and INR were noted.
Thus from the animal study, but also from the 2 clinical studies mentioned, there is ample reason to believe that bone marrow cells may have a therapeutic stem cell population that is useful for treatment of liver disease. Whether this occurs by transdifferentiation of hematopoietic stem cells into hepatocytes, by differentiation of hepatocyte progenitors from the bone marrow into hepatocytes in the liver, or by immune modulation mediated by bone marrow derived mesenchymal cells, is not really relevant. It is known that bone marrow has a therapeutic cell population for this deadly disease, and this should be further investigated.