Increasing Bone Marrow Transplant Success Rate

Researchers at Cincinnati Children's Hospital Medical Center discovered that the pharmacological inhibition of a signaling pathway triggered by the epidermal growth factor receptor, increased the mobilization of blood stem cells in mice.

This discovery could lead to a well-targeted therapy that could improve the success rates of bone marrow transplants.

Hartmut Geiger, PhD, a researcher in the division of Experimental Hematology/Cancer Biology at Cincinnati Children's and senior investigator on the study, and his colleagues worked with recombinant inbred mice for this study.

The reason is quite simple: most of the knowledge about the cellular and molecular regulation of G-CSF(granulocyte colony stimulating factor)-induced stem cells comes from mouse studies.

Because the process of this signaling protein, which stimulates hematopoietic stem and progenitor cells, is not altered by evolution, inbred mouse strains are valid replacements for studies, and the conclusions can be extended to humans.

This study came from the researchers' previously published research, which identified a region on chromosome 11 in the mouse model that regulates G-CSF-induced mobilization of hematopoietic stem cells.

In this region, out of the 12 genes present, the test results identified Egfr - a protein involved in triggering molecular reactions that regulate cell growth, multiplication and migration.

The scientists experimented on the G-CSF/Egfr pathway and its influence on stem cell stimulation in different ways, that included genetic manipulation and pharmacological intervention.

In one experiment, when scientists used an anti-cancer drug (Erlotinib) that blocks the Egfr pathway to stimulate HSC mobilization, the mice undergoing bone marrow transplant had a five-times higher stem cell mobilization.

Dr Geiger suggested that this could be “a possible application of these findings into the clinic,” and added that “experiments are already planned to test whether this novel treatment for enhancing HSC mobilization might translate into novel therapies for patients.”

These results are extremely important for the improvement of the effectiveness of autologous bone marrow transplants, or basically the self-transplant of stem cells.

“Up to 10 percent of bone marrow donors fail to mobilize sufficient numbers of stem cells, which impedes autologous transplants and significantly delays transplant recovery time,” reminded Dr Geiger.

“Our findings reveal a new rationale for targeted pharmacological approaches to improve stem cell mobilization and transplantation outcomes,” he added.

Autologous bone marrow transplant is often used in people who have received radiation therapy in cancer treatments, to help restore their hematologic system, damaged by the radiation.

The researchers' findings were reported September 26, in Nature Medicine.