PROVIDING A MICROENVIRONMENT FOR THE DEVELOPMENT OF HUMAN CD34-CELLS IN SCID MICE( HEMATOPOIETIC)

In order to develop a convenient small-animal model that can support t he differentiation of human bone-marrow-derived CD34+ cells, we transp lanted SCID mice with an immortalized human stromal cell line, Lof(11- 10). The Lof(11-10) cell line has been characterized to produce human cytokines capable of supporting primitive human hematopoietic cell pro liferation in vitro. Intraperitoneal injection of Lof(11-10) cells int o irradiated SCID mice by itself resulted in a dose-dependent survival of the mice from lethal irradiation. The radioprotective survival was reflected by an increase in the growth and number of mouse bone-marro w-derived committed hematopoietic progenitors. The Lof(11-10) cells lo calized to the spleen, but not to the bone marrow of these animals and resulted in detectable levels of circulating human IL-6 in their plas ma. Secondary intravenous injections of either human or simian CD34+ c ells into the Lof(11-10)-transplanted SCID mice resulted in engraftmen t of injected cells within the bone marrow of these mice. The utility of this small-animal model that allows the growth and differentiation of human CD34+ cells and its potential use in clinical gene therapy pr otocols are discussed.