This prompted Dr. Geiger and his colleagues to search for therapeutic targets that would boost stem cell mobilization. They work with specially bred mice (recombinant inbred mice) in their research because much of the current knowledge about cellular and molecular regulation of G-CSF-induced stem cells comes from mouse studies. Because the G-CSF process that mobilizes hematopoietic stem and progenitor cells is conserved through evolution between mice and humans, inbred mouse strains are valuable surrogates for studies that can be translated to people.
Working from their previously published research, the scientists were able track a region on chromosome 11 in their mouse models that regulates G-CSF-induced mobilization of HSCs. Of 12 genes located in this region, testing pointed to Egfr, which is a protein involved in triggering molecular reactions that regulate cell growth, multiplication and migration. Mutations in Egfr have also been linked to cancer.
The researchers tested the G-CSF/Egfr pathway's influence on stem cell mobilization in several ways, including genetic manipulation and pharmacologic intervention. In one key experiment, involving mice undergoing bone marrow transplant, the researchers used an anti-cancer drug (Erlotinib) that blocks the Egfr pathway to enhance HSC mobilization. These mice experienced a 5-fold increase in stem cell mobilization.
"This suggests a possible application of these findings into the clinic," Dr, Geiger said. "Experiments are already planned to test whether this novel treatment for enhancing HSC mobilization might translate into novel therapies for patients."
|Contact: Nick Miller|
Cincinnati Children's Hospital Medical Center