Multipotential mesenchymal stromal/stem cells in skeletal tissue repair

Mesenchymal stromal/stem cells (MSC) are increasingly becoming a prime candidate for tissue engineering and regenerative medicine due to the unique combination of their accessibility, multipotency, paracrine effects, and immunomodulatory properties. MSC are a subpopulation of clonogenic marrow stromal cells originally identified in the 1960s, and are now thought to reside in a quiescent state within a perivascular niche within the bone marrow microenvironment. The function of MSC during normal bone homeostasis/remodeling is to instigate bone formation through their differentiation into osteoblasts, which has also led to the investigation of how MSC may be utilized specifically in skeletal tissue repair. Skeletal tissues include not only bone and cartilage, but also tendon and ligament tissue. A multitude of approaches using MSC in different skeletal tissue engineering applications have been performed in small and larger animal pre-clinical models, where some of this work has been extended to early human clinical trials with varying success. One strategy utilizes endogenous MSC through the application of soluble cytokines, growth factors or hormones to stimulate local MSC proliferation and differentiation. Alternatively, the isolation of exogenous MSC has been studied more extensively, ranging from freshly isolated or culture expanded autologous, allogeneic or genetically modified MSC. These populations have then been delivered either by systemic infusion or directly into the site of injury in combination with a variety of biocompatible scaffold materials only or additionally supplemented with cytokines, growth factors or hormones. While a number of approaches have proven to be clinically efficacious in skeletal repair, a standardized approach for the repair of specific skeletal tissues is yet to be elucidated. The present chapter summarizes the isolation, characterization and application of MSC for skeletal tissue regeneration.