During embryogenesis, the close relationship between hematopoietic stem cells and the developing vascular system suggests the existence of a common precursor cell during early development. In the adult, the bone marrow is the principal site of steady state hematopoiesis. We now show that hematopoiesis can be induced in normal adult blood vessels. Our data demonstrate that the transplantation of segments of adult vena cava or thoracic aorta protects mice from lethal irradiation. Blood vessel derived progenitor cells migrate to the spleens or recipient animals where they give rise to day 14 CFU-S with the same frequency observed following the transplantation of normal bone marrow. Donor derived cells are readily detected in the peripheral blood and spleen of recipient mice and multilineage progeny of these blood vessel derived cells have been demonstrated. In addition, vascular tissue grafts substantially protect host hematopoiesis from the effects of radiation. These findings indicate the presence of a previously unknown reservoir of cells with hematopoietic potential in the blood vessels of normal adult mice. To further evaluate the biologic activity of this cell population(s) we propose to: 1) Characterize the early activation and migration of blood vessel derived cells with hematopoietic activity; 2) Evaluate the functional activity and transplantation potential of blood vessel derived hematopoietic cells and 3) Isolate and characterize populations of phenotypically and functionally defined blood vessel associated stem cells.
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