chapter  10
18 Pages

Human/Sheep Hematopoietic Chimeras

I. INTRODUCTION Autologous or allogeneic hematopoietic stem cell (HSC) transplantation has been used successfully in the treatment of congenital and acquired immunodeficiencies, hematological and metabolic disorders, and neoplasias of children and adult patients (1-5). Historically, the bone marrow has represented the main source of HSCs in pediatric and adult individuals. However, in many cases, a matched marrow donor cannot be found, thus limiting the applicability of this life-saving procedure (6-7). This and the fact that the use of allogeneic HSCs frequently results in graft-versus-host disease (GVHD) have led to a search for alternative sources of HSCs for use in human transplantations. Three sources of human HSCs have been identified: fetal liver, cord blood, and peripheral blood. Of these, cord blood and peripheral blood are considered to be practical sources of HSCs, especially since methods exist which can mobilize significant numbers of stem/progenitor cells into the circulation (8-12). Cord blood is not only a rich source of HSCs, but its use in children with malignant and nonmalignant diseases has been associated with a relatively low incidence of GVHD (8,10,11). Acute GVHD appears to be due to hoste, reactive donor T lymphocytes (13,14). Depletion of T cells from the donor’s graft can significantly decrease the incidence of GVHD (15-18). However, in most instances, this has led to an increasing number of graft rejections, leukemic relapses, and mixed chimerisms (17). To circumvent these difficulties and to devise better therapeutic strategies of HSC transplantation, considerable effort has been devoted to the isolation and characterization of stem/progenitor cell populations.