Autologous Mesenchymal Stroma Cells Are Superior to Allogeneic Ones in Bone Defect Regeneration.
Autologous Mesenchymal Stroma Cells Are Superior to Allogeneic Ones in Bone Defect Regeneration.
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DOI：
10.3390/ijms19092526
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发表时间：
2018-08-25
影响因子：
5.6
通讯作者：
Ignatius A
中科院分区：
文献类型：
--
作者：
Rapp AE;Bindl R;Erbacher A;Kruchen A;Rojewski M;Schrezenmeier H;Müller I;Ignatius A
应用自体骨髓间充质干细胞(MSC)治疗骨缺损需要两次侵入性手术和数周的细胞体外扩增。为了克服这些局限性，使用同种异体骨髓间充质干细胞可能是有吸引力的，因为它们有望获得免疫保护。由于使用不同动物模型的临床前研究在异基因MSC的有效性方面相互矛盾，我们调查了自体和同种异体人MSC(HMSC)在类似人类免疫系统的人源化小鼠模型中再生骨的效果是否相同。将自体和同种异体hMSC应用于严重股骨缺损区，我们发现同种异体hMSC在植入后早期可引起轻微的免疫反应，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移植的骨形成比自体hMSC少，与成骨因子Runx2表达减少和血管生成障碍有关。通过对I型胶原α-2的物种特异性染色，我们发现两种来源的MSCs都不能合成新的骨基质，这表明移植的hMSC对骨再生有间接贡献。综上所述，我们的研究结果表明，自体hMSC在骨缺损治疗中的应用优于同种异体细胞。
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.
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