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

Journal Article · · Transplantation; (United States)
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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.

Research Organization:
Radiobiological Institute TNO, Rijswijk, The Netherlands
OSTI ID:
5004644
Journal Information:
Transplantation; (United States), Journal Name: Transplantation; (United States) Vol. 3; ISSN TRPLA
Country of Publication:
United States
Language:
English

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Related Subjects

560151 -- Radiation Effects on Animals-- Man
560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANEMIAS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL MODELS
BODY
BONE MARROW
DISEASES
EXTERNAL IRRADIATION
HEMATOPOIETIC SYSTEM
HEMIC DISEASES
IMMUNOSUPPRESSION
IRRADIATION
MAMMALS
MICE
ORGANS
PATIENTS
RODENTS
SYMPTOMS
THALASSEMIA
THERAPY
TISSUES
TRANSPLANTS
VERTEBRATES
WHOLE-BODY IRRADIATION