Department of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL, USA.
Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA.
Nat Biomed Eng. 2022 Jan;6(1):54-66. doi: 10.1038/s41551-021-00740-x. Epub 2021 Jun 3.
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.
精确理解和控制微环境线索可以用于优化细胞治疗的疗效。在这里，我们表明，单层涂覆有柔软顺应性凝胶的间充质基质细胞 (MSCs) 呈现出明确的化学机械线索，可通过分泌可溶性间质胶原酶来响应肿瘤坏死因子 α (TNF-α) 的存在来促进基质重塑。在患有纤维化肺损伤的小鼠中，用涂覆的 MSC 治疗可维持肺组织中正常的胶原蛋白水平、纤维密度和微弹性，并且凝胶中持续呈现重组 TNF-α 有助于在宿主炎症消退时逆转细胞异常组织重塑。具有预定化学机械线索的凝胶涂层可用于对具有特定作用机制的细胞进行定制，以获得所需的治疗效果。
