Ranganath, Sudhir H.Tong, ZhixiangLevy, OrenMartyn, KeirKarp, Jeffrey M.Inamdar, Maneesha S.2016-07-142016Ranganath, Sudhir H., Zhixiang Tong, Oren Levy, Keir Martyn, Jeffrey M. Karp, and Maneesha S. Inamdar. 2016. “Controlled Inhibition of the Mesenchymal Stromal Cell Pro-inflammatory Secretome via Microparticle Engineering.” Stem Cell Reports 6 (6): 926-939. doi:10.1016/j.stemcr.2016.05.003. http://dx.doi.org/10.1016/j.stemcr.2016.05.003.2213-6711http://nrs.harvard.edu/urn-3:HUL.InstRepos:27662152Summary Mesenchymal stromal cells (MSCs) are promising therapeutic candidates given their potent immunomodulatory and anti-inflammatory secretome. However, controlling the MSC secretome post-transplantation is considered a major challenge that hinders their clinical efficacy. To address this, we used a microparticle-based engineering approach to non-genetically modulate pro-inflammatory pathways in human MSCs (hMSCs) under simulated inflammatory conditions. Here we show that microparticles loaded with TPCA-1, a small-molecule NF-κB inhibitor, when delivered to hMSCs can attenuate secretion of pro-inflammatory factors for at least 6 days in vitro. Conditioned medium (CM) derived from TPCA-1-loaded hMSCs also showed reduced ability to attract human monocytes and prevented differentiation of human cardiac fibroblasts to myofibroblasts, compared with CM from untreated or TPCA-1-preconditioned hMSCs. Thus, we provide a broadly applicable bioengineering solution to facilitate intracellular sustained release of agents that modulate signaling. We propose that this approach could be harnessed to improve control over MSC secretome post-transplantation, especially to prevent adverse remodeling post-myocardial infarction.en-USJournal Article2016-07-1410.1016/j.stemcr.2016.05.003