Host cell mobilization for in situ tissue regeneration

Although small, localized injuries can be healed through the body's normal reparative process, large traumatic injury overwhelms this system and may result in a deficit of functional recovery, despite the use of conventional reconstructive modalities. Cell-based approaches using tissue engineering and regenerative medicine techniques have offered new opportunities for treatment. Although the fundamental principles of cell-based therapies have been demonstrated clinically on multiple tissue systems, usually a donor tissue biopsy and ex vivo cell manipulation prior to implantation in vivo are necessary. The goal of the present study was to investigate whether host biologic resources and environmental conditions could be used for in situ tissue regeneration, which may eliminate the need for donor cell procurement and subsequent in vitro cell manipulation. To address this aim, we implanted a common biomaterial into mice and characterized the infiltrating cells to determine their regenerative potential. We showed that host cell infiltrates are not entirely comprised of inflammatory and fibroblast-like cells and the normal inflammatory process can be altered by incorporating anti-inflammatory agents that influence the formation of scar tissue. In addition, the infiltrating cells are capable of differentiating into multiple cell lineages, including osteogenic, myogenic, adipogenic, and endothelial lineages, if appropriate conditions are provided. These results suggest that it is possible to recruit a predominance of cells with multilineage potential into a biomaterial scaffold. Therefore, it may be possible to enrich the infiltrate with such cell types and control their fate, provided the proper substrate-mediated signaling can be imparted into the scaffold for in situ tissue regeneration.