Induction of Mixed Chimerism through Transplantation of CD45-Congenic Mobilized Peripheral Blood Stem Cells after Nonmyeloablative Irradiation  Zvonimir.

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Induction of Mixed Chimerism through Transplantation of CD45-Congenic Mobilized Peripheral Blood Stem Cells after Nonmyeloablative Irradiation  Zvonimir Koporc, Sinda Bigenzahn, Peter Blaha, Elahi Fariborz, Edgar Selzer, Megan Sykes, Ferdinand Muehlbacher, Thomas Wekerle  Biology of Blood and Marrow Transplantation  Volume 12, Issue 3, Pages 284-292 (March 2006) DOI: 10.1016/j.bbmt.2005.11.011 Copyright © 2006 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Transplantation of PBSCs leads to significantly lower levels of long-term chimerism in comparison with BMT after nonmyeloablative TBI. CD45.1 mice (n = 6/group) received either 20 × 106 CD45.2 BMC (A, B, C) or 20 × 106 CD45.2 mPBSCs (D, E, F) after various doses of TBI (2 Gy [A,D], 1.5 Gy [B, E], or 1 Gy [C, F). The percentages of donor-derived CD4+ cells, CD8+ cells, B cells, monocytes/granulocytes, and NK cells among white blood cells were evaluated by FCM at different time points and are shown as means. Levels of chimerism induced with mPBSCs were significantly lower than those induced with BMCs treated with the same TBI dose (A vs D, B vs E, and C vs F; P < .05). HSCT denotes hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation 2006 12, 284-292DOI: (10.1016/j.bbmt.2005.11.011) Copyright © 2006 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Transplantation of similar numbers of c-kit+ mPBSCs and c-kit+ BMCs still led to differences in chimerism levels. CD45.1 mice (n = 6/group) received either 10 × 106 CD45.2 BMCs (A, C) or 30 × 106 CD45.2 mPBSCs (B, D) with 1.5 Gy of TBI. In this manner, similar numbers of c-kit+ cells were transplanted in both groups (according to the percentage of c-kit+ cells as determined by FCM analysis among unseparated mPBSCs and BMCs). To evaluate whether the lower chimerism induced in mPBSCT recipients is due to a remaining alloresponse against CD45.2, or to other antigenic differences, some groups received immunosuppression (C, D) (rapa, MP, and MMF for four weeks), others remained untreated (A, B). Chimerism levels in various lineages as determined by FCM analysis over time are shown as means. *P < .05 indicates a significant difference in chimerism between the BMT and mPBSC transplantation groups (A vs B and C vs D). IS treatment did not significantly improve levels of chimerism (P = NS in any lineage) by either BMT or mPBSC transplantation (A vs C or B vs D). HSCT denotes hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation 2006 12, 284-292DOI: (10.1016/j.bbmt.2005.11.011) Copyright © 2006 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Levels of chimerism induced in BMC and mPBSC recipients correlated with the number of transplanted progenitor cells as estimated from CFU assays. Chimerism per transplanted progenitor cell was calculated as described in detail in the Methods section. A significant difference in percentage of chimerism per 1 × 104 transplanted progenitor cells, between BMC and mPBSC recipients (A vs B) is noticeable only in the first few weeks after HSCT (C), probably due to the larger percentage of CD4+ and CD8+ cells contained in mPBSC. Data are from the same experiment for which results are also shown in Figure 3. HSCT denotes hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation 2006 12, 284-292DOI: (10.1016/j.bbmt.2005.11.011) Copyright © 2006 American Society for Blood and Marrow Transplantation Terms and Conditions