Navigation Links
Inhibiting cell signaling pathway may improve bone marrow transplant success rate

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 process to further improve the treatment.

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

Related biology news :

1. Inhibiting serotonin in gut could cure osteoporosis
2. New strategy for inhibiting virus replication
3. Corrosion-inhibiting coatings containing good bacteria
4. Inhibiting proteins may prevent cartilage breakdown in arthritis patients
5. The bonsai effect: Wounded plants make jasmonates, inhibiting cell division, stunting growth
6. LSUHSC awarded patent for compound inhibiting cancer and other diseases
7. Investigators discover a new hot spot for the genesis of signaling neurons in the adult brain
8. New molecular signaling cascade increases glucose uptake
9. Scientists post lower speed limit for cell-signaling protein assembly
10. Insulin signaling key to caste development in bees
11. Cell signaling classification system gives researchers new tool
Post Your Comments:
(Date:11/12/2015)... 11, 2015   Growing need for low-cost, ... has been paving the way for use of ... discrete analytes in clinical, agricultural, environmental, food and ... used in medical applications, however, their adoption is ... to continuous emphasis on improving product quality and ...
(Date:11/9/2015)... , Nov. 09, 2015 ... addition of the "Global Law Enforcement ... offering. --> ) has ... Law Enforcement Biometrics Market 2015-2019" report ... and Markets ( ) has announced ...
(Date:10/29/2015)... 2015   MedNet Solutions , an innovative SaaS-based ... clinical research, is pleased to announce that it has ... as one of only three finalists for a ... and Growing" category. The Tekne Awards honor Minnesota ... technology innovation and leadership. iMedNet™ eClinical ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... , Nov. 25, 2015 /PRNewswire/ - Aeterna Zentaris ... that its business and prospects remain fundamentally strong ... Zoptrex™ (zoptarelin doxorubicin) recently received DSMB recommendation to ... completion following review of the final interim efficacy ... 2 Primary Endpoint in men with heavily pretreated ...
(Date:11/25/2015)... The Global Genomics Industry ... and in-depth study on the current state of ... ) , The report provides ... classifications, applications and industry chain structure. The Genomics ... including development trends, competitive landscape analysis, and key ...
(Date:11/24/2015)... ... November 24, 2015 , ... The United States Golf Association (USGA) today ... Green Section Award. Presented annually since 1961, the USGA Green Section Award recognizes an ... turfgrass. , Clarke, of Iselin, N.J., is an extension specialist of turfgrass ...
(Date:11/24/2015)... 2015 /CNW/ - iCo Therapeutics ("iCo" or "the Company") ... for the quarter ended September 30, 2015. Amounts, ... and presented under International Financial Reporting Standards ("IFRS"). ... said Andrew Rae , President & CEO ... not only value enriching for this clinical program, ...
Breaking Biology Technology: