PMID- 16503497 OWN - NLM STAT- MEDLINE DCOM- 20060622 LR - 20171116 IS - 1083-8791 (Print) IS - 1083-8791 (Linking) VI - 12 IP - 3 DP - 2006 Mar TI - Induction of mixed chimerism through transplantation of CD45-congenic mobilized peripheral blood stem cells after nonmyeloablative irradiation. PG - 284-92 AB - Clinical translation of the mixed-chimerism approach for inducing transplantation tolerance would be facilitated if mobilized peripheral blood stem cells (mPBSCs) could be used instead of bone marrow cells (BMCs). Because the use of mPBSCs for this purpose has not been investigated in nonmyeloablative murine protocols, we explored the engraftment potential of mPBSCs in a CD45-congenic model as a first step. After 2, 1.5, or 1 Gy of total body irradiation, CD45.1 B6 hosts received unseparated granulocyte colony-stimulating factor-mobilized CD45.2 B6 PBSCs or unseparated CD45.2 B6 BMCs. The same total cell numbers, or aliquots of mPBSCs and BMCs containing similar numbers of c-kit+ cells, were transplanted both with and without a short course of rapamycin-based immunosuppression (IS). Transplantation of mPBSCs induced long-term multilineage macrochimerism, but chimerism levels were significantly lower than among recipients of the same number of BMCs. Transplanting aliquots containing similar numbers of c-kit+ cells reduced the difference between mPBSCs and BMCs, but lower levels of chimerism were nonetheless observed in mPBSC recipients. Chimerism levels correlated more closely with the number of transplanted progenitor cells as determined by colony-forming unit assays. IS did not affect chimerism levels, indicating that the donor CD45 isoform or other minor disparities do not pose a major barrier to engraftment. Our findings indicate that under nonmyeloablative conditions, progenitor cells contained in mPBSCs have an engraftment capacity similar to progenitor cells from BMCs, allowing induction of lasting mixed chimerism with moderate cell numbers. On a cell-per-cell basis, unseparated BMCs have some advantages that may be minimized if the number of progenitor cells is equalized. These results are expected to facilitate the development of mPBSC-based allogeneic tolerance protocols. FAU - Koporc, Zvonimir AU - Koporc Z AD - Division of Transplantation, Department of Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria. FAU - Bigenzahn, Sinda AU - Bigenzahn S FAU - Blaha, Peter AU - Blaha P FAU - Fariborz, Elahi AU - Fariborz E FAU - Selzer, Edgar AU - Selzer E FAU - Sykes, Megan AU - Sykes M FAU - Muehlbacher, Ferdinand AU - Muehlbacher F FAU - Wekerle, Thomas AU - Wekerle T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biol Blood Marrow Transplant JT - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JID - 9600628 RN - EC 3.1.3.48 (Leukocyte Common Antigens) SB - IM MH - Animals MH - Female MH - *Hematopoietic Stem Cell Mobilization/methods MH - *Leukocyte Common Antigens MH - Mice MH - *Peripheral Blood Stem Cell Transplantation/methods MH - *Transplantation Chimera MH - *Transplantation Conditioning/methods MH - Transplantation, Homologous MH - Whole-Body Irradiation/methods EDAT- 2006/03/01 09:00 MHDA- 2006/06/23 09:00 CRDT- 2006/03/01 09:00 PHST- 2005/09/22 00:00 [received] PHST- 2005/11/29 00:00 [accepted] PHST- 2006/03/01 09:00 [pubmed] PHST- 2006/06/23 09:00 [medline] PHST- 2006/03/01 09:00 [entrez] AID - S1083-8791(05)00812-8 [pii] AID - 10.1016/j.bbmt.2005.11.011 [doi] PST - ppublish SO - Biol Blood Marrow Transplant. 2006 Mar;12(3):284-92. doi: 10.1016/j.bbmt.2005.11.011.