Suppression of the immune system as a critical step for bone formation from allogeneic osteoprogenitors implanted in rats.
Suppression of the immune system as a critical step for bone formation from allogeneic osteoprogenitors implanted in rats.
复制标题
DOI：
10.1111/jcmm.12172
复制
发表时间：
2014-01
影响因子：
5.3
通讯作者：
de Boer J
中科院分区：
文献类型：
--
作者：
Chatterjea A;LaPointe VL;Alblas J;Chatterjea S;van Blitterswijk CA;de Boer J
间充质基质细胞（MSCs）的表面标志物表明它们可以逃避同种异体宿主免疫系统的检测。这可能是骨再生应用的最佳策略，其中现成的细胞可以植入以修复骨缺损。然而，尚不清楚MSC预分化为成骨谱系（一种改善骨形成的手段）如何影响其免疫原性。在大鼠异位种植模型中使用免疫组织学技术，我们证明同种异体骨祖细胞安装T细胞和B细胞介导的免疫反应，导致体内骨形成的情况下。通过每日给予免疫抑制剂FK506抑制宿主免疫应答，可有效预防对同种异体骨祖细胞的免疫攻击。在免疫抑制的环境中，同种异体骨祖细胞能够以与同基因细胞相似的量生成骨。然而，使用来自其中一个同种异体供体的骨祖细胞导致新沉积的骨受到宿主免疫系统的攻击，尽管继续施用免疫抑制剂。这表明，尽管使用免疫抑制剂可以潜在地抑制对同种异体细胞的免疫攻击，但优化免疫抑制剂的剂量对于确保同种异体环境中的骨形成可能是至关重要的。总之，包含源自同种异体MSC的骨祖细胞的同种异体移植物具有用于骨再生应用的潜力。
The surface marker profile of mesenchymal stromal cells (MSCs) suggests that they can escape detection by the immune system of an allogeneic host. This could be an optimal strategy for bone regeneration applications, where off-the-shelf cells could be implanted to heal bone defects. However, it is unknown how pre-differentiation of MSCs to an osteogenic lineage, a means of improving bone formation, affects their immunogenicity. Using immunohistological techniques in a rat ectopic implantation model, we demonstrate that allogeneic osteoprogenitors mount a T cell- and B cell-mediated immune response resulting in an absence of in vivo bone formation. Suppression of the host immune response with daily administration of an immunosuppressant, FK506, is effective in preventing the immune attack on the allogeneic osteoprogenitors. In the immunosuppressed environment, the allogeneic osteoprogenitors are capable of generating bone in amounts similar to those of syngeneic cells. However, using osteoprogenitors from one of the allogeneic donors led to newly deposited bone that was attacked by the host immune system, despite the continued administration of the immunosuppressant. This suggests that, although using an immunosuppressant can potentially suppress the immune attack on the allogeneic cells, optimizing the dose of the immunosuppressant may be crucial to ensure bone formation within the allogeneic environment. Overall, allografts comprising osteoprogenitors derived from allogeneic MSCs have the potential to be used in bone regeneration applications.
登录
查看更多内容
影响因子：
4.3
作者：
Shen, Zhong-Yang;Zhang, Jing;Zheng, Wei-Ping
通讯作者：
Zheng, Wei-Ping
影响因子：
14
作者：
Mentink, Anouk;Hulsman, Marc;de Boer, Jan
通讯作者：
de Boer, Jan
影响因子：
4.4
作者：
Liu, Hua;Kemeny, David Michael;Cao, Tong
通讯作者：
Cao, Tong
影响因子：
6.2
作者：
Taira, M;Inaba, M;Ikehara, S
通讯作者：
Ikehara, S
影响因子：
6.2
作者：
Larsen, Kenneth H.;Frederiksen, Casper M.;Kassem, Moustapha
通讯作者：
Kassem, Moustapha