Identification and Manipulation of HSC Niche Components
Hematopoiesis and hematopoietic stem cells are dependent upon regulation from the bone marrow microenvironment. The specific components of the bone marrow required for HSC support have been termed the HSC niche. Our laboratory and others have previously identified multiple cellular niche components that include osteolineage cells, endothelial cells, mesenchymal stem cells and adipocytes.
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Aging and the Bone Marrow Microenvironment
Aging is associated with hematopoietic failure. Though the number of hematopoietic stem cells in the marrow increases with age, their functional ability to repopulate the hematopoietic system decreases. Changes to the bone marrow microenvironment, including bone loss and the age related disease osteoporosis, coincide with the observed decrease in hematopoietic stem cell function.
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Microenvironmental Regulation of Malignancy
In many hematopoietic malignancies development of cytopenias is a major cause of morbidity and mortality. While the bone marrow microenvironment is essential for the regulation of normal hematopoiesis, little is known about the reliance of leukemic cells on microenvironmental regulation. We have previously used a mouse model of myeloid leukemia to demonstrate a significant loss of osteoblastic cells in the bone marrow.
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Mitigation of Radiation Injury
The hematopoietic system is extremely sensitive to radiation, and hematopoietic failure is one of the leading causes of mortality following acute radiation injury. Hematopoietic stem cell function requires support from a complex microenvironment in the bone marrow, and targeting microenvironmental components provides mitigation strategies to decrease acute, and late effects of radiation on the hematopoietic system.
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