Berner Arne, Henkel Jan, Woodruff Maria A, Steck Roland, Nerlich Michael, Schuetz Michael A, Hutmacher Dietmar W
Institute of Health and Biomedical Innovation and Medical Engineering Research Facility, Queensland University of Technology, Brisbane, Queensland, Australia; Department of Trauma Surgery, University of Regensburg, Regensburg, Germany.
Institute of Health and Biomedical Innovation and Medical Engineering Research Facility, Queensland University of Technology, Brisbane, Queensland, Australia; Department of Trauma Surgery, University of Regensburg, Regensburg, Germany
Stem Cells Transl Med. 2015 May;4(5):503-12. doi: 10.5966/sctm.2014-0244. Epub 2015 Apr 1.
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.
基于细胞的组织工程方法是再生医学领域中很有前景的策略。然而，细胞递送方式仍然是一个令人担忧的问题，需要显著改进。在骨缺损形成后，通常立即将负载细胞的支架和/或基质移植到骨缺损处。此时，营养和氧气供应不足，炎症级联反应被激发，从而为移植细胞的存活和参与再生过程创造了极不利的微环境。因此，我们开发了一种独特的治疗理念，即延迟注射同种异体骨髓基质细胞（BMSC）片来修复绵羊的临界尺寸胫骨缺损，以研究在炎症后期引入细胞时其再生潜力的效果。与预先接种支架/细胞构建体组和仅支架组相比，在缺损手术后4周将同种异体BMSC微创经皮注射到可生物降解复合支架中，可显著改善骨再生。生物力学测试和微型计算机断层扫描显示的结果与临床参考标准（即自体骨移植）相当。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表明，延迟同种异体细胞移植可为未来具有挑战性的骨缺损提供适用的临床治疗替代方案的。
