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

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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.