Abstract
Stem cells provide tremendous promise for the development of new therapeutic approaches for musculoskeletal conditions. In addition to their multipotency, certain types of stem cells exhibit immunomodulatory effects that can mitigate inflammation and enhance tissue repair. However, the translation of stem cell therapies to clinical practice has proven difficult due to challenges in intradonor and interdonor variability, engraftment, variability in recipient microenvironment and patient indications, and limited therapeutic biological activity. In this regard, the success of stem cell-based therapies may benefit from cellular engineering approaches to enhance factors such as purification, homing and cell survival, trophic effects, or immunomodulatory signaling. By combining recent advances in gene editing, synthetic biology, and tissue engineering, the potential exists to create new classes of "designer" cells that have prescribed cell-surface molecules and receptors as well as synthetic gene circuits that provide for autoregulated drug delivery or enhanced tissue repair. Published by Wiley Periodicals, Inc. J Orthop Res 37:1287-1293, 2019.