Immunological aspects of mesenchymal stem cell -based bone regeneration and the risk for osteomyelitis

基于间充质干细胞的骨再生的免疫学方面和骨髓炎的风险

• 批准号: 168979004
• 负责人: Professorin Dr. Wiltrud Richter
• 金额: --
• 依托单位: Klinik für Orthopädie und Unfallchirurgie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/168979004?language=en
• 关键词: Immunological; aspects; mesenchymal; stem; cell

Adult mesenchymal stem cells (MSC) have successfully been used to enhance regeneration of large bone defects. However, expanded MSC are known to exert immunosuppressive activity in vitro and in vivo. Large bone lesions which could benefit from MSC-based treatment approaches show a considerable rate of spontaneous infection which facilitates the development of osteomyelitis. So far, no studies have addressed how transplantation of MSC affects the local immune response during fracture healing. Therefore, we want to investigate whether the transplantation of expanded MSC is accompanied by an increased degree of osteomyelitis and whether activation of MSC by microbial-derived molecules and inflammatory mediators limits their positive effects on bone repair. We will further determine whether combined treatment with the antimicrobial peptide LL-37, which has immunostimulatory and angiogenic properties can prevent these effects, contain osteomyelitis and improve bone healing. If so, transplantation of MSC in a biomaterial augmented with LL-37 could represent an attractive new strategy to improve bone healing and minimize the risk for the development of osteomyelitis.

成体间充质干细胞（MSC）已成功用于增强大骨缺损的再生。然而，已知扩增的 MSC 在体外和体内发挥免疫抑制活性。可以受益于基于间充质干细胞的治疗方法的大骨病变显示出相当高的自发感染率，这促进了骨髓炎的发展。迄今为止，还没有研究探讨间充质干细胞移植如何影响骨折愈合过程中的局部免疫反应。因此，我们想要研究扩增的间充质干细胞的移植是否伴随着骨髓炎程度的加重，以及微生物衍生的分子和炎症介质对间充质干细胞的激活是否限制了它们对骨修复的积极作用。我们将进一步确定与具有免疫刺激和血管生成特性的抗菌肽 LL-37 联合治疗是否可以预防这些影响、遏制骨髓炎并改善骨愈合。如果是这样，将 MSC 移植到添加了 LL-37 的生物材料中可能代表一种有吸引力的新策略，可改善骨愈合并最大限度地降低发生骨髓炎的风险。