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Autologous Mesenchymal Stroma Cells Are Superior to Allogeneic Ones in Bone Defect Regeneration

1
Institute of Orthopaedic Research and Biomechanics, Trauma Research Center Ulm, University of Ulm, 89081 Ulm, Germany
2
Department of General Paediatrics, Haematology, and Oncology, University Children’s Hospital Tübingen, 72076 Tübingen, Germany
3
Division for Pediatric Stem Cell Stem Cell Transplantation and Immunology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany
4
Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service, Baden Wuerttemberg-Hessen and University Hospital Ulm, 89081 Ulm, Germany
5
Institute of Transfusion Medicine, University of Ulm, 89081 Ulm, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Current Address: German Rheumatism Research Center, Berlin and Department of Rheumatology and Clinical Immunology, Charité–Universitätsmedizin Berlin, 10117 Berlin, Germany.
Int. J. Mol. Sci. 2018, 19(9), 2526; https://doi.org/10.3390/ijms19092526
Received: 22 June 2018 / Revised: 10 August 2018 / Accepted: 22 August 2018 / Published: 25 August 2018
(This article belongs to the Special Issue Biological Basis of Musculoskeletal Regeneration)
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Abstract

The application of autologous mesenchymal stem cells (MSC) for the treatment of bone defects requires two invasive procedures and several weeks of ex vivo cell expansion. To overcome these limitations, the administration of allogeneic MSC may be attractive, because they are anticipated to be immunoprivileged. Because preclinical studies using various animal models are conflicting with respect to the efficacy of allogeneic MSC, we investigated whether autologous and allogeneic human MSC (hMSC) are equally effective in regenerating bone in a humanized mouse model resembling the human immune system. Applying autologous and allogeneic hMSC in critically sized femoral defects, we found that allogeneic hMSC elicited a mild immune response early after implantation, whereas early angiogenic processes were similar in both treatments. At later healing time points, the transplantation of allogeneic hMSC resulted in less bone formation than autologous hMSC, associated with a reduced expression of the osteogenic factor Runx2 and impaired angiogenesis. We found by species-specific staining for collagen-type-1α2 that MSCs of either source did not synthesize new bone matrix, indicating an indirect contribution of transplanted hMSC to bone regeneration. In conclusion, our data suggest that the application of autologous hMSC is superior to that of allogeneic cells for bone defect treatment. View Full-Text
Keywords: bone regeneration; large bone defect; humanized mouse; allogeneic; stem cells; MSC bone regeneration; large bone defect; humanized mouse; allogeneic; stem cells; MSC
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Rapp, A.E.; Bindl, R.; Erbacher, A.; Kruchen, A.; Rojewski, M.; Schrezenmeier, H.; Müller, I.; Ignatius, A. Autologous Mesenchymal Stroma Cells Are Superior to Allogeneic Ones in Bone Defect Regeneration. Int. J. Mol. Sci. 2018, 19, 2526.

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