Safety Assessment of Mesenchymal Stem Cells in Musculoskeletal Implantation

There has been a rapid increase in our understanding in the isolation, culture and application of mesenchymal stem cells (MSC). Despite an increased understanding of MSC biology and new avenues for in vivo application - the standardization of laboratory practices for MSC is lacking. One particular example is in the examination of safety issues in MSC in vivo implantation. The following review will explore the current laboratory practices for the safety assessments of MSC implantation, from diverse viewpoints of such as histopathology, cytopathology, and cytogenetics. A snapshot of current practices and techniques is presented across three common types of MSC differentiation: bone, cartilage, and muscle tissue. Overall, we uncovered a relative lack of investigation of safety issues in MSC implantation. For example, cell proliferation and local inflammation were only assessed in less than one third of manuscripts. Additionally, the average length of study was less than two weeks, a short period limited in its detection of adverse outcomes. The present review uncovers a relative paucity of papers that place emphasis on safety outcomes for animal studies. Given the potential role of MSC in sarcomagenesis and other tumorigenesis, the routine performance safety assays for MSC mediated tissue engineering studies will facilitate the future translation to clinical use. Finally, we provide a set of practical preliminary suggestions is presented for safety assessments in MSC implantation models. In summary, in order to bridge the gap in translation from animal to human, increased practice and routinization of safety assessments in MSC implantation will be beneficial.

Keywords: Bone engineering, cartilage engineering, chondrogenesis, mesenchymal stem cells, MSC, muscle engineering, myogenesis, osteogenesis, safety, sarcomagenesis, stem cells, tissue engineering, toxicity, tumorigenesis