Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model
Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model
复制标题
DOI：
10.5966/sctm.2014-0244
复制
发表时间：
2015-05-01
影响因子：
6
通讯作者：
Hutmacher, Dietmar W.
中科院分区：
文献类型：
--
作者：
Berner, Arne;Henkel, Jan;Hutmacher, Dietmar W.
基于细胞的组织工程方法是再生医学领域中很有前途的策略。然而，细胞递送的方式仍然是一个值得关注的问题，需要显著改进。载有细胞的支架和/或基质通常在骨缺损形成后立即移植到骨缺损中。此时，营养和氧气供应不足，引发炎症级联反应，从而为移植细胞的生存和参与再生过程创造了一个非常不利的微环境。因此，我们开发了一种独特的治疗概念，使用延迟注射同种异体骨髓基质细胞（BMSC）片来再生绵羊的一个临界大小的胫骨缺损，以研究在炎症后阶段引入细胞再生潜力的影响。缺损术后4周经皮微创注射同种异体骨髓间充质干细胞到可生物降解复合支架中，与预先植入支架/细胞构建组和仅支架组相比，骨再生明显改善。生物力学测试和微计算机断层扫描显示与临床参考标准（即自体骨移植）相当的结果。据我们所知，我们是第一个在经过验证的临床前大型动物模型中证明延迟同种异体细胞移植可以为未来具有挑战性的骨缺陷提供适用的临床治疗方案的人。
Cell-based tissue engineering approaches are promising strategies in the field of regenerative medicine. However, the mode of cell delivery is still a concern and needs to be significantly improved. Scaffolds and/or matrices loaded with cells are often transplanted into a bone defect immediately after the defect has been created. At this point, the nutrient and oxygen supply is low and the inflammatory cascade is incited, thus creating a highly unfavorable microenvironment for transplanted cells to survive and participate in the regeneration process. We therefore developed a unique treatment concept using the delayed injection of allogenic bone marrow stromal cell (BMSC) sheets to regenerate a critical-sized tibial defect in sheep to study the effect of the cells' regeneration potential when introduced at a postinflammatory stage. Minimally invasive percutaneous injection of allogenic BMSCs into biodegradable composite scaffolds 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed comparable results to the clinical reference standard (i.e., an autologous bone graft). To our knowledge, we are the first to show in a validated preclinical large animal model that delayed allogenic cell transplantation can provide applicable clinical treatment alternatives for challenging bone defects in the future.