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Accession Number ADA575580
Title Gap Junction Intercellular Communication in Bone Marrow Failure.
Publication Date Oct 2012
Media Count 21p
Personal Author J. Cancelas
Abstract The mechanisms responsible for both acquired and inherited bone marrow failure (BMF) are not yet understood. Although most inherited BMF syndromes can be linked to specific genetic defects, these defects do not fully explain the range of physical characteristics observed in affected individuals. In addition, animal models for observed BMF genetic defects have not been able to fully recreate the associated syndromes. With support from a Fiscal Year 2010 Bone Marrow Failure Research Program Exploration Hypothesis Development Award, Dr. Cancelas is investigating whether BMF syndromes are related to a defect in cell-to-cell communication between mesenchymal stem cells and progenitors (MSC/P) and hematopoietic stem cells (HSC). Blood cell formation in the bone marrow (hematopoiesis) is dependent on the close association of HSC and the surrounding microenvironment, of which MSC/P are a major component.Natural causes such as aging, or external insults, such as radiation, toxin exposure, or chemotherapy, are known to cause DNA damage and affect HSC activity, which may in part be due to hematopoietic stress from increasing cellular levels of reactive oxygen species (ROS). Fanconi anemia and Schwachman- Diamond syndrome are two BMF syndromes with defects in DNA repair enzyme systems, making individuals with these syndromes highly sensitive to DNA- damaging events. However, researchers suspect that modifier genes or traits are responsible for the differences in the severity of these diseases and their relation to skeletal malformations in BMF syndromes. Using a model of DNA damage induced by chemotherapy-induced ROS production, Dr. Cancelas tested the ability of HSC to resume blood formation after hematopoietic stress. His results indicated that hematopoietic recovery is delayed when HSC are deficient in connexin-43 (Cx43), a gap junction protein involved in cell-to-cell communication and highly expressed in HSC and MSC/P.
Keywords Anemias
Blood
Blood cells
Bmf(Bone marrow failure)
Bone marrow
Cells(Biology)
Connective tissue
Damage
Defects(Materials)
Deoxyribonucleic acids
Diseases
Embryos
Enzymes
Failure
Genetics
Hematopoiesis
Hematopoietic system
Hsc(Hematopoietic stem cells)
Msc/p(Mesenchymal stem cells and progenitors)
Precursors
Radiation
Signs and symptoms
Stem cells
Stresses
Toxins and antitoxins


 
Source Agency Non Paid ADAS
NTIS Subject Category 57E - Clinical Medicine
57W - Stress Physiology
Corporate Author Children's Hospital Medical Center, Cincinnati, OH.
Document Type Technical report
Title Note Final rept. 1 Apr 2011-30 Sep 2012.
NTIS Issue Number 1319
Contract Number W81XWH-11-1-0296

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