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

成体间充质干细胞（MSC）已成功地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。可以从基于MSC的治疗方法中受益的大骨病变显示出相当高的自发性感染率，这促进了骨髓炎的发展。到目前为止，还没有研究涉及MSC移植如何影响骨折愈合过程中的局部免疫反应。因此，我们想研究扩增的MSC的移植是否伴随着骨髓炎程度的增加，以及微生物衍生的分子和炎症介质对MSC的激活是否限制了它们对骨修复的积极作用。我们将进一步确定是否与具有免疫刺激和血管生成特性的抗菌肽LL-37联合治疗可以预防这些作用，抑制骨髓炎并改善骨愈合。如果是这样的话，MSC在LL-37增强的生物材料中的移植可能代表一种有吸引力的新策略，以改善骨愈合并最大限度地降低骨髓炎发展的风险。

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.