Allogeneic Non-Adherent Bone Marrow Cells Facilitate Hematopoietic Recovery but Do Not Lead to Allogeneic Engraftment |
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Authors: | Stephan Fricke Manuela Ackermann Alexandra Stolzing Christoph Schimmelpfennig Nadja Hilger Jutta Jahns Guido Hildebrandt Frank Emmrich Peter Ruschpler Claudia P?sel Manja Kamprad Ulrich Sack |
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Institution: | 1. Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.; 2. Institute of Clinical Immunology and Transfusion Medicine, University of Leipzig, Leipzig, Germany.; 3. Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany.; 4. Clinic for Radiation Therapy and Radiation Oncology, University of Leipzig, Leipzig, Germany.; 5. Clinic for Radiation Therapy, University of Rostock, Rostock, Germany.;University of Sheffield, United Kingdom |
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Abstract: | BackgroundNon adherent bone marrow derived cells (NA-BMCs) have recently been described to give rise to multiple mesenchymal phenotypes and have an impact in tissue regeneration. Therefore, the effects of murine bone marrow derived NA-BMCs were investigated with regard to engraftment capacities in allogeneic and syngeneic stem cell transplantation using transgenic, human CD4+, murine CD4−/−, HLA-DR3+ mice.Methodology/Principal FindingsBone marrow cells were harvested from C57Bl/6 and Balb/c wild-type mice, expanded to NA-BMCs for 4 days and characterized by flow cytometry before transplantation in lethally irradiated recipient mice. Chimerism was detected using flow cytometry for MHC-I (H-2Db], H-2Kd]), mu/huCD4, and huHLA-DR3). Culturing of bone marrow cells in a dexamethasone containing DMEM medium induced expansion of non adherent cells expressing CD11b, CD45, and CD90. Analysis of the CD45+ showed depletion of CD4+, CD8+, CD19+, and CD117+ cells. Expanded syngeneic and allogeneic NA-BMCs were transplanted into triple transgenic mice. Syngeneic NA-BMCs protected 83% of mice from death (n = 8, CD4+ donor chimerism of 5.8±2.4% day 40], P<.001). Allogeneic NA-BMCs preserved 62.5% (n = 8) of mice from death without detectable hematopoietic donor chimerism. Transplantation of syngeneic bone marrow cells preserved 100%, transplantation of allogeneic bone marrow cells 33% of mice from death.Conclusions/SignificanceNA-BMCs triggered endogenous hematopoiesis and induced faster recovery compared to bone marrow controls. These findings may be of relevance in the refinement of strategies in the treatment of hematological malignancies. |
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