Durable engraftment and development of human hematopoietic lineages in normal mammals

摘要

A non-human chimeric mammal M4 having long-term stable xenogeneic hematopoietic cells, is obtained by doubly transplanting a mammal M1, the hematopoietic cells of which have been substantially suppressed or destroyed, with hematopoietic cells from at least two different sources, at least one of these sources being hematopoietic cells originating in a mammal M3 of a species other than that of mammal M1, preferably human, and at least a second of these sources being hematopoietic cells originating from a mammal M2, of a species other than that of M3, preferably of the same species as M1, having a genetically-determined hematopoietic deficiency. In particular, a chimeric mouse having long term stable human B and T cells was obtained by double engraftment of human bone marrow cells and of bone marrow cells derived from a mouse with severe combined immunodeficiency (SCID).