Inhibition of aberrant tissue remodelling by mesenchymal stromal cells singly coated with soft gels presenting defined chemomechanical cues

用呈现明确化学机械线索的软凝胶单独包被的间充质基质细胞抑制异常组织重塑

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作者:Sing Wan Wong, Chandramohan R Tamatam #, Ik Sung Cho #, Peter T Toth, Raymond Bargi, Patrick Belvitch, James C Lee, Jalees Rehman, Sekhar P Reddy, Jae-Won Shin

Abstract

The precise understanding and control of microenvironmental cues could be used to optimize the efficacy of cell therapeutics. Here, we show that mesenchymal stromal cells (MSCs) singly coated with a soft conformal gel presenting defined chemomechanical cues promote matrix remodelling by secreting soluble interstitial collagenases in response to the presence of tumour necrosis factor alpha (TNF-α). In mice with fibrotic lung injury, treatment with the coated MSCs maintained normal collagen levels, fibre density and microelasticity in lung tissue, and the continuous presentation of recombinant TNF-α in the gel facilitated the reversal of aberrant tissue remodelling by the cells when inflammation subsided in the host. Gel coatings with predefined chemomechanical cues could be used to tailor cells with specific mechanisms of action for desired therapeutic outcomes.

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