CINCINNATI Identification of a molecular communications pathway that influences the mobilization of hematopoietic (blood) stem cells could lead to targeted therapies for improving bone marrow transplant success rates.
In a bed-side to bench approach, researchers at Cincinnati Children's Hospital Medical Center report Sept. 26 in Nature Medicine that pharmacological inhibition of a signaling pathway triggered by Egfr (epidermal growth factor receptor) increased the mobilization of hematopoietic stem cells in mice. The finding provides a scientific basis for enhancing the effectiveness of autologous bone marrow transplants, in which the recipient donates his or her own stem cells prior to the procedure.
"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," said Hartmut Geiger, Ph.D., a researcher in the division of Experimental Hematology/Cancer Biology at Cincinnati Children's and senior investigator on the study. "Our findings reveal a new rationale for targeted pharmacological approaches to improve stem cell mobilization and transplantation outcomes."
Autologous bone marrow transplant is often used to restore a person's hematologic system after receiving radiation therapy for cancer treatment. Radiation exposure damages the system, which produces all of the body's blood cell types including those vital to immune system function.
In clinical hematopoietic stem cell (HSC) transplants, the preferred source for mobilizing hematopoietic stem cells from bone marrow into peripheral circulating blood is by targeting a signaling protein called granulocyte colony stimulating factor, or G-CSF. G-CSF stimulates bone marrow so that it releases HSCs into circulating peripheral blood. Mobilization failures and delayed recovery rates suggest the need for a deeper molecular understanding of the mobilization
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Cincinnati Children's Hospital Medical Center