Controlled Inhibition of the Mesenchymal Stromal Cell Pro-inflammatory Secretome via Microparticle Engineering
Author(s)Ranganath, Sudhir H.; Tong, Zhixiang; Levy, Oren; Martyn, Keir; Karp, Jeffrey M.; Inamdar, Maneesha S.; ... Show more Show less
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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.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT
Stem Cell Reports
Ranganath, Sudhir H.; Tong, Zhixiang; Levy, Oren; et al. "Controlled Inhibition of the Mesenchymal Stromal Cell Pro-inflammatory Secretome via Microparticle Engineering." Stem Cell Reports 6, no 6. (June 2016): 926-939.
Final published version