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Title: Cure of murine thalassemia by bone marrow transplantation without eradication of endogenous stem cells

alpha-Thalassemic heterozygous (Hbath/+) mice were used to investigate the possible selective advantage of transplanted normal (+/+) hemopoietic cells. Without conditioning by total-body irradiation (TBI), infusion of large numbers of normal bone marrow cells failed to correct the thalassemic peripheral blood phenotype. Since the recipients' stem cells are normal with respect to number and differentiation capacity, it was thought that the transplanted stem cells were not able to lodge, or that they were not stimulated to proliferate. Therefore, a nonlethal dose of TBI was given to temporarily reduce endogenous stem cell numbers and hemopoiesis. TBI doses of 2 or 3 Gy followed by infusion of normal bone marrow cells proved to be effective in replacing the thalassemic red cells by normal red cells, whereas a dose of 1 Gy was ineffective. It is concluded that cure of thalassemia by bone marrow transplantation does not necessarily require eradication of thalassemic stem cells. Consequently, the objectives of conditioning regimens for bone marrow transplantation of thalassemic patients (and possibly other nonmalignant hemopoietic disorders) should be reconsidered.
Authors:
; ;
Publication Date:
OSTI Identifier:
5004644
Resource Type:
Journal Article
Resource Relation:
Journal Name: Transplantation; (United States); Journal Volume: 3
Research Org:
Radiobiological Institute TNO, Rijswijk, The Netherlands
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; BONE MARROW; TRANSPLANTS; THALASSEMIA; THERAPY; BIOLOGICAL MODELS; IMMUNOSUPPRESSION; MICE; PATIENTS; WHOLE-BODY IRRADIATION; ANEMIAS; ANIMAL TISSUES; ANIMALS; BODY; DISEASES; EXTERNAL IRRADIATION; HEMATOPOIETIC SYSTEM; HEMIC DISEASES; IRRADIATION; MAMMALS; ORGANS; RODENTS; SYMPTOMS; TISSUES; VERTEBRATES 560152* -- Radiation Effects on Animals-- Animals; 560151 -- Radiation Effects on Animals-- Man