Adult blood vessels restore host hematopoiesis following lethal irradiation.

ABSTRACT

OBJECTIVE: Accumulating evidence indicates a common stem cell may be responsible for both vasculogenesis and blood cell production during early embryologic development, yet little is known about the fate of these cells during ontogeny. We sought to determine whether hematopoietic potential is associated with normal blood vessels in the adult. MATERIALS AND METHODS: Segments of adult thoracic aorta or inferior vena cava were transplanted under the kidney capsule of lethally irradiated recipients (1100 cGy). Radioprotection, colony-forming units (CFUs), and the extent of donor-derived hematopoietic constitution were evaluated using both Ly5 congenic and ROSA26 donor mice. RESULTS: As little as 10 mg of transplanted vascular tissue radioprotected 80% of recipients, gave rise to similar numbers of CFUs as 10(5) bone marrow cells and prevented the development of severe anemia. Bromodeoxyuridine labeling studies revealed cell proliferation within the intima of donor vascular tissue within 48 hours of transplantation. ROSA26 donor-derived vascular cells migrated to the recipient spleen; however, CFUs were of host origin, a finding confirmed using sex-mismatched transplants. Although donor-derived cells were readily detected in the peripheral blood 2 to 3 weeks after transplant, they rapidly declined in frequency to approximately 1.0% by 4 weeks and persisted at these levels for more than 1 year. Bone marrow from rescued primary recipients provided radioprotection after transplantation into secondary recipients; however, only CD3(+) donor-derived cells were detected. CONCLUSION: These findings demonstrate the presence of a population of cells within normal adult vascular tissue that has the capacity to protect host hematopoietic stem cells from radiation-induced death.