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

Abstract

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:
Research Org.:
Radiobiological Institute TNO, Rijswijk, The Netherlands
OSTI Identifier:
5004644
Resource Type:
Journal Article
Resource Relation:
Journal Name: Transplantation; (United States); Journal Volume: 3
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

Citation Formats

Wagemaker, G., Visser, T.P., and van Bekkum, D.W. Cure of murine thalassemia by bone marrow transplantation without eradication of endogenous stem cells. United States: N. p., 1986. Web. doi:10.1097/00007890-198609000-00004.
Wagemaker, G., Visser, T.P., & van Bekkum, D.W. Cure of murine thalassemia by bone marrow transplantation without eradication of endogenous stem cells. United States. doi:10.1097/00007890-198609000-00004.
Wagemaker, G., Visser, T.P., and van Bekkum, D.W. 1986. "Cure of murine thalassemia by bone marrow transplantation without eradication of endogenous stem cells". United States. doi:10.1097/00007890-198609000-00004.
@article{osti_5004644,
title = {Cure of murine thalassemia by bone marrow transplantation without eradication of endogenous stem cells},
author = {Wagemaker, G. and Visser, T.P. and van Bekkum, D.W.},
abstractNote = {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.},
doi = {10.1097/00007890-198609000-00004},
journal = {Transplantation; (United States)},
number = ,
volume = 3,
place = {United States},
year = 1986,
month = 9
}
  • KHT tumor cells were mixed with mouse bone marrow to simulate a sample of bone marrow containing metastatic tumor cells. This mixture was separated into a bone marrow fraction and a tumor cell fraction by centrifugal elutriation. Elutriation did not change the transplantability of the bone marrow stem cells as measured by a spleen colony assay and an in vitro erythroid burst forming unit assay. The tumorogenicity of the KHT cells was similarly unaffected by elutriation. The data showed that bone marrow cells could be purified to less than 1 tumor cell in more than 10/sup 6/ bone marrow cells.more » Therefore, purification of bone marrow removed prior to lethal radiation-drug combined therapy for subsequent autologous transplantation appears to be feasible using modifications of this method if similar physical differences between human metastatic tumor cells and human bone marrow cells exist. This possibility is presently being explored.« less
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