Abstract
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 (β2m−/− mouse strains prevent engraftment even after IBMT. In contrast, combining the robustness of the NOD/SCID IL-2Rγ−/− 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-2Rγ−/− 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.
Acknowledgments
This work was funded by the CSJA (0029 and 0030 to PM) and CICE (P08-CTS-3678 to PM) de la Junta de Andalucia, The Spanish Ministry of Health, to PM (PI070026) and CB (CP07/00059). We thank Dr Dominique Bonnet (Cancer Research UK, London, UK) for providing the NOD/SCID β2m−/− mice.
Authorship and disclosures: CB designed and performed experiments, analyzed the data and wrote the manuscript. RM performed experiments and analyzed the data. TC and IG-A performed in vivo transplants and supervised animals. PM conceived and supervised the study and wrote the paper. The authors report no potential conflicts of interest.