Institute of Orthopaedic Research and Biomechanics, Trauma Research Center Ulm, University of Ulm, 89081 Ulm, Germany.
Department of General Paediatrics, Haematology, and Oncology, University Children's Hospital Tübingen, 72076 Tübingen, Germany.
Int J Mol Sci. 2018 Aug 25;19(9):2526. doi: 10.3390/ijms19092526.
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.
自体间充质干细胞 (MSC) 应用于骨缺损的治疗需要进行两次有创操作和数周的体外细胞扩增。为了克服这些限制，同种异体 MSC 的给药可能具有吸引力，因为它们预计具有免疫特权。由于使用各种动物模型的临床前研究对同种异体 MSC 的疗效存在冲突，我们研究了自体和同种异体人 MSC（hMSC）在类似于人类免疫系统的人源化小鼠模型中再生骨方面是否同样有效。我们在临界尺寸股骨缺损中应用自体和同种异体 hMSC，发现同种异体 hMSC 在植入后早期引发轻度免疫反应，而两种治疗方法的早期血管生成过程相似。在较晚的愈合时间点，同种异体 hMSC 的移植导致的骨形成少于自体 hMSC，与成骨因子 Runx2 的表达降低和血管生成受损有关。我们通过针对胶原型-1α2 的种属特异性染色发现，两种来源的 MSC 均未合成新的骨基质，表明移植的 hMSC 对骨再生的间接贡献。总之，我们的数据表明，自体 hMSC 的应用优于同种异体细胞用于骨缺损治疗。
