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

成人间充质干细胞(MSC)已被成功地用于促进大段骨缺损的再生。然而，已知扩增的MSC在体外和体内都具有免疫抑制活性。可以从基于MSC的治疗方法中受益的大型骨损伤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，还没有研究表明移植间充质干细胞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MSC移植是否伴随着骨髓炎程度的增加，以及微生物衍生分子和炎症介质激活MSC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，遏制骨髓炎和促进骨愈合。如果是这样的话，将骨髓间充质干细胞移植到含有LL-37的生物材料中可能是一种有吸引力的新策略，可以改善骨愈合并将骨髓炎的风险降至最低。

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.