Experimental study of normal and diseased human hematopoiesis in the model of fetal thymus and bone marrow grafts in SCID mice Volume 3, issue 4, Juillet - Août 1997


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Human fetal thymus and bone are rapidly vascularized, then maintained on the long term on heterotopic transplantation in SCID mice. Hematopoiesis is sustained in these grafts, yet only transiently in the thymus. Human thymopoiesis in SCID mice can be, however, protracted if an appropriate source of precursors, such as an adjacent fetal liver graft, is made available. Such models, in which the architecture of human blood-forming tissues is preserved, are amenable to the experimental study of human normal and pathologic hematopoiesis. Roles plaid by distinct thymus stromal cell compartments in the selection of functional, alloreactive T cells have been studied in chimeric thymus grafts. HIV infection of the human thymus in SCID-hu mice has permitted to decipher the cellular events leading to thymus depletion in AIDS. The effect of various growth factors on medullary hematopoiesis could also be directly analyzed in humanized SCID mice. Finally, primary human blood-forming tissues implanted in SCID mice have yielded assay systems for sorted normal and transgenic hematopoietic stem and precursor cells.