Intra-bone marrow transplantation of human CD34+ cells into NOD/LtSz- scid IL-2rγnull mice permits multilineage engraftment without previous irradiation

• Published in: Cytotherapy (Oxford, England) Vol. 12; no. 1; pp. 45 - 49
• Main Authors: Bueno, Clara, Montes, Rosa, de la Cueva, Teresa, Gutierrez-Aránda, Iván, Menendez, Pablo
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 2010; Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS)
• Subjects: Advanced Basic Science; CD34+ cells; engraftment; irradiation; NOD/SCID mouse strains; NODILtSz-scid IL-2Rγnull; Other; engraftment; CD34 + cells; NOD/SCID mouse strains; NODILtSz-scid IL-2Rγ null; irradiation; NODILtSz-scid IL-2Rγnull; CD34+ cells
• ISSN: 1465-3249; 1477-2566
• DOI: 10.3109/14653240903377052

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.