Adult Human Stem Cells Treat Liver Failure in Mice

Hepatology, May 15, 2009

Scientists have demonstrated the ability of human cord blood stem cells to regenerate damaged liver tissue in mice. Led by Dr. Ping Zhou, the study was conducted by researchers at the UC-Davis Medical Center in Sacramento in collaboration with scientists at the Washington University School of Medicine in St. Louis and the Krembil Center for Stem Cell Biology at the Robarts Research Institute in Ontario, Canada.

Human cord blood stem cells (hCBSCs) are already known to generate hepatocyte-like cells, and human patients who receive autologous bone marrow transplants as a treatment for liver failure have been found to exhibit clinical improvement in pilot trials. It had not been previously demonstrated, however, whether the hCBSC-derived cells are capable of transdifferentiating directly into hepatocytes, or if other mechanisms are at work that merely allow for the fusion of the cells with recipient hepatocytes.

In the current study, Dr. Zhou and his colleagues investigated the action of hCBSCs with beta-glucoronidase-deficient nonobese diabetic/severe combined immunodeficient/ mucopolysaccharidosis type VII (NOD/SCID/MPSVII) mice to whom carbon tetrachloride had been administered to induce liver damage. Using human umbilical cord blood stem cells that had been selected for aldehyde dehydrogenase activity, which correlates with high stem cell activity, the scientists found that the human progenitor cells with high aldehyde dehydrogenase activity engrafted into the damaged liver tissue with an efficiency rate of 3% to 14.2%, while actual fusion of the human cells to the mouse cells was found to be very rare. Additionally, it was observed that the cells in the target mouse tissue expressed a number of human hepatic markers such as albumin, hepatocyte nuclear factor 1 protein, and liver-specific alpha 1-antitrypsin messenger RNA, and the majority of the albumin-expressing cells of human origin also contained mouse genetic material, thereby further indicating engraftment of the human cells to the mouse tissue. As the researchers noted, the procedure thereby "improved recovery of the mice from toxic insult".

As the authors concluded, "hCBSCs or their progeny may home to the injured liver and release trophic factors that hasten tissue repair, whereas fusion of these cells with hepatocytes may occur rarely and contribute to a lesser extent to liver repair."

One reviewer of the study, in StemCellPatents.com, further suggests the supplemental administration of G-CSF (granulocyte-colony stimulating factor), a known stem cell mobilizer which was already shown by Piscaglia et al. in Italy to accelerate liver regeneration. Also recommended is the continued investigation of CD34+ adult stem cells, found in abundance in umbilical cord blood, which have already yielded positive results in the treatment of liver failure as demonstrated by Pai et al. in London in 2008.