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Conditioning Regimens

Optimal protocol for total body irradiation for allogeneic bone marrow transplantation in mice

Bone Marrow Transplantation volume 30, pages 843–849 (2002)Cite this article

Abstract

We have previously demonstrated, using chimeric resistant MRL/lpr mice, that a fractionated total body irradiation (FTBI) (5 Gy × 2 with a 4 h interval on the day before allogeneic bone marrow transplantation (BMT)) is the best conditioning regimen for the treatment of autoimmune diseases in radiosensitive MRL/lpr mice. In the present study, using various standard strains of mice (not radiosensitive mice), we explore the best protocol for irradiation (doses and intervals) as the conditioning regimen for allogeneic BMT. Recipient mice were exposed to various irradiation regimens: a single total body irradiation (TBI) of 9.5 or 12 Gy and FTBI of (5+5) Gy to (7+7) Gy with a 1 to 24 h interval. The method generally utilized for humans ((2+2) Gy with a 4 h interval for 3 days (total 12 Gy)) was also used. One day after the last irradiation, donor BMCs from BALB/c, C3H, or C57BL/6 (B6) mice were transplanted into C3H or B6 mice. The irradiation protocol of (2+2) Gy for 3 days was found to be insufficient to enable the complete removal of recipient immunocompetent cells, since donor-reactive T cells were observed in the recipient spleens and many recipient-type NK and CD4+ cells were also detected in the recipient hematolymphoid tissues. In all the combinations, the highest survival rate was achieved in the recipients irradiated with (6+6) or (6.5+6.5) Gy with a 4 h interval. In the surviving mice, the hematolymphoid tissues had been fully reconstituted with donor cells.

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Acknowledgements

The work was supported by grants from the Ministry of Health and Welfare of Japan, the Ministry of Education, Science and Culture, and the Japan Private School Promotion Foundation. We thank Mr H Eastwick-Field and Ms K Ando for assistance in manuscript preparation. We also thank Ms M Shinkawa and Ms Y Tokuyama for their technical assistance. The work was supported by grants from the Ministry of Health and Welfare of Japan, the Ministry of Education, Science and Culture, and the Japan Private School Promotion Foundation, a grant from the ‘Haiteku Research Center’ of the Ministry of Education, grant-in-aid for scientific research (B) 11470062, grants-in-aid for scientific research on priority areas (A) 10181225 and (A) 1162221, Setsuro Fuji Memorial, the Osaka Foundation for Promotion of Fundamental Medical Research, a grant from the ‘Millennium’ program of the Ministry of Education, Culture, Sports, Sciences and Technology, a grant from the ‘Science Frontier’ program of the Ministry of Education, Culture, Sports, Sciences and Technology, and also a grant from Japan Immunoresearch Laboratories Co., Ltd (JIMRO).

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Authors and Affiliations

  1. First Department of Pathology, Kansai Medical University, Moriguchi, Osaka, Japan

    Y-Z Cui, H Hisha, G-X Yang, T-X Fan, T Jin, Q Li, Z Lian & S Ikehara

  2. Transplantation Center, Kansai Medical University, Moriguchi, Osaka, Japan

    H Hisha & S Ikehara

  3. Regeneration Research Center for Intractable Diseases, Kansai Medical University, Moriguchi, Osaka, Japan

    H Hisha & S Ikehara

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  1. Y-Z Cui
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  2. H Hisha
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  7. Z Lian
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  8. S Ikehara
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Cui, YZ., Hisha, H., Yang, GX. et al. Optimal protocol for total body irradiation for allogeneic bone marrow transplantation in mice. Bone Marrow Transplant 30, 843–849 (2002). https://doi.org/10.1038/sj.bmt.1703766

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  • DOI: https://doi.org/10.1038/sj.bmt.1703766

Keywords

  • bone marrow transplantation
  • fractionated irradiation
  • reconstitution

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