Specific Exogenous Activation of Mesenchymal Stromal Cells Maximizes their Therapeutic Potential to Modulate Inflammation
Mesenchymal stromal cells (MSCs) are adult stem cells that are attractive as a cellular therapeutic due to their many beneficial effects, such as modulating immune/inflammatory responses in many diseases and after injury. Although the safety of MSC therapy has been demonstrated in humans, most of the cells injected don’t migrate to the site of inflammation and get cleared from the body rapidly. Therefore, very large and often repeated doses are needed. Additionally, these cells need to be stimulated by external signals to impart their beneficial effects. It is not clear the degree to which this may be happening in the body, especially when only a small fraction of cells make it to the target tissue, or when the amount of stimulatory factors in the environment may be relatively low. Therefore, we hypothesize that activating and immobilizing the MSCs prior to transplantation can improve the efficacy of MSC therapies. In this study, the activation of MSCs by a panel of inflammatory molecules and the effects of these on MSC immunomodulation was investigated in a macrophage model of inflammation. Two factors were identified as optimal for activating the MSC to increase their ability to transition macrophages from a pro- to an anti-inflammatory state. This approach will also be investigated using MSCs encapsulated in alginate microspheres. The continuance of this work will result in the creation of an immobilized, activated MSC therapy that maximizes their efficacy in human patients.