Navigation Links
Inhibiting cell signaling pathway may improve bone marrow transplant success rate
Date:9/26/2010

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
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:2/14/2017)... , Feb. 14, 2017  Wake Forest Baptist ... as its new chief executive officer (CEO). Freischlag joins ... John D. McConnell , M.D., who last year ... at the Medical Center, after leading it since 2008. ... full scope of Wake Forest Baptist,s academic health system, ...
(Date:2/8/2017)... NEW YORK , Feb. 8, 2017 /PRNewswire/ ... an individual,s voice to match it against a ... voice such as pitch, cadence, and tone are ... systems require minimal hardware installation, as most PCs ... remotely for different transactions. Voice recognition biometrics are ...
(Date:2/7/2017)... Minn. , Feb. 7, 2017   MedNet ... supports the entire spectrum of clinical research, is pleased ... iMedNet , its innovative, highly flexible and award ... iMedNet customers. iMedNet is a proven ... provides Electronic Data Capture (EDC), but also delivers an ...
Breaking Biology News(10 mins):
(Date:2/24/2017)... ... ... Chef Jodi Abel has returned from her three-week tour through the ... a number of delicious recipes and new techniques to share with her Lajollacooks4u guests. ... province. It is internationally renowned for its incredible wine farms, beautiful environment, boutiques ...
(Date:2/24/2017)... SAN DIEGO , Feb. 24, 2017  Aethlon ... the following note authored by its Chairman and CEO, ... address at the Munich Security Conference last Saturday, ... engineered virus could kill more people than nuclear weapons. ... by U.S. and U.K. intelligence agencies, that scientific terrorists ...
(Date:2/24/2017)... 24, 2017  Driven by consumers, preference towards ... the fastest growing categories, finds the recently published ... Personal Care: Multi-regional Market Analysis and Opportunities ... firm Kline. "Biotechnology actives are derived ... more effective for skin and hair care applications," ...
(Date:2/24/2017)... ... , ... FireflySci, Inc is an explosive small business that continues to grow ... bringing their powerful cuvette and spectrophotometer calibration to the spectroscopy world. ... on as they add yet another mark on the global map. , With distributors ...
Breaking Biology Technology: