Stem Cell Mobilization is lifesaving in an animal model of Acute Liver Failure
*Andrew Cameron, *Anthony Mark, *Daniel Warren, G. Melville Williams, *Robert Montgomery
The Johns Hopkins University School of Medicine, Baltimore, MD
OBJECTIVE(S): No therapy except liver transplantation currently exists for patients with Acute Liver Failure (ALF). Our laboratory studies stem cells in liver disease and our aim was to examine whether stem cell mobilization would aid in liver repair and survival benefit in an animal model of ALF.
METHODS: Mice were treated with a single near-lethal intraperitoneal injection of carbon tetrachloride (CCl4). Twelve hours later mice were randomized to receive either Mozibil and G-CSF (agents known to mobilize marrow derived stem cells) or saline vehicle injection. Mice were followed for survival as well as evidence of liver injury by transaminase level and histopathology.
RESULTS: With control treatment only 25% of animals were alive within 2 days of CCl4 exposure, consistent with our established near-lethal model of ALF. In contrast, the group that received treatment with agents that mobilize stem cells displayed 87% survival (n=8, p < 0.05).
CONCLUSIONS: Our results demonstrate a possible therapy for patients with Acute Liver Failure, a group for whom liver transplant or death are often the only alternatives. This therapy exerts its action via mobilization of marrow derived stem cells which participate in liver recovery. This process may help avoid liver transplant in patients with acute liver failure and aid a wide variety of medical and surgical patients with liver injury.