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Title: Controlled Inhibition of the Mesenchymal Stromal Cell Pro-inflammatory Secretome via Microparticle Engineering
Authors: Ranganath, Sudhir H.
Tong, Zhixiang
Levy, Oren
Martyn, Keir
Karp, Jeffrey M.
Inamdar, Maneesha S.
Keywords: Cell Biology
Mediated Cardiac Protection
Stem/Stromal Cells
Issue Date: 2016
Publisher: Cell Press
Citation: Ranganath, S. H.; Tong, Z. X.; Levy, O.; Martyn, K.; Karp, J. M.; Inamdar, M. S., Controlled Inhibition of the Mesenchymal Stromal Cell Pro-inflammatory Secretome via Microparticle Engineering. Stem Cell Reports 2016, 6 (6), 926-939
Stem Cell Reports
Abstract: 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 smallmolecule NF-kB 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.
Description: Open Access
ISSN: 2213-6711
Appears in Collections:Research Papers (Maneesha S. Inamdar)

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