Journal
CYTOTHERAPY
Volume 12, Issue 1, Pages 45-49Publisher
ELSEVIER SCI LTD
DOI: 10.3109/14653240903377052
Keywords
CD34(+) cells; engraftment; NOD/SCID mouse strains; NOD/LtSz-scid IL-2R gamma(null); irradiation
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Funding
- CSJA [0029, 0030]
- CICE [P08-CTS-3678]
- Spanish Ministry of Health [PI070026, CP07/00059]
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Background aims. Non-irradiated immunodeficient recipients provide the best physiologic setting for revealing hematopoietic stem cell (HSC) functions after xenotransplantion. An approach that efficiently permits the detection of human hematopoietic repopulating cells in non-irradiated recipients is therefore highly desired. Methods. We compared side-by-side the ability to reconstitute hematopoiesis via intra-bone marrow transplantation (IBMT) in three commonly used mouse strains avoiding previous irradiation. Results. Non-irradiated NOD/SCID and NOD/SCID beta 2m-/- mouse strains prevent engraftment even after IBMT. In contrast, combining the robustness of the NOD/SCID IL-2R gamma-/- recipient with the sensitivity of IBMT facilitates the detection, without previous host irradiation, of human SCID-repopulating cells 10 weeks after transplantation. The level of chimerism averaged 14% and multilineage engraftment (lymphoid dominant) was observed consistently in all mice. Analysis of injected and non-injected bones, spleen and peripheral blood demonstrated that engrafting cells were capable of in vivo migration and expansion. Conclusions. Combining the robustness of the NOD/SCID IL-2R gamma-/- mouse strain with the sensitivity of IBMT strongly facilitates long-term multilineage engraftment and migration for human CD34(+) cells without the need for previous irradiation.
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