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  3. Cell surface engineering with a pseudofibrotic ECM reprograms the antifibrotic activity of mesenchymal stromal cells

Cell surface engineering with a pseudofibrotic ECM reprograms the antifibrotic activity of mesenchymal stromal cells

  • Sci Adv. 2026 Jan 16;12(3):eaea0998. doi: 10.1126/sciadv.aea0998.
Xianghua Zhong 1,  Xinchao Liu 1,  Jiajia Luo 1,  Xinyang Liu 1,  Xueting Wei 1,  Xi Peng 1,  Lu Wang 2,  Huaimin Wang 3,  Kunyu Zhang 1 4 5,  Liming Bian 1 4 5,  Peng Shi 1 4 5
Affiliations

Affiliations

  • 1 School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, P. R. China.
  • 2 Center of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, P. R. China.
  • 3 Department of Chemistry, School of Science, Westlake University, Hangzhou 310024, P. R. China.
  • 4 National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, P. R. China.
  • 5 Guangdong Provincial Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006, P. R. China.
PMID: 41544160 DOI: 10.1126/sciadv.aea0998
Abstract

Fibrotic diseases, which impair tissue function and contribute to organ failure, remain a major clinical challenge with limited treatment options. Mesenchymal stromal cells (MSCs) offer promise for antifibrotic therapy via paracrine signaling, but their clinical efficacy is hindered by poor survival and limited functional activity after transplantation. Here, we present a cell surface engineering strategy that reprograms the antifibrotic function of MSCs by constructing a pseudofibrotic extracellular matrix (ECM) on their surface. Through in situ self-assembly of peptide-modified hyaluronic acid, we generate a nanofiber-based matrix that mimics the dense, disordered architecture of fibrotic ECM. This matrix activates the Piezo1/PI3K-Akt signaling pathway, inducing up-regulation of Mmp13-a key collagen-degrading matrix metalloproteinase-in engineered MSCs. In a rat model of myocardial infarction-associated fibrosis, engineered MSCs exhibit robust antifibrotic activity compared to unmodified MSCs. These findings establish a bioinspired strategy for MSC reprogramming and offer a path toward more effective cell-based therapies for fibrotic disease.

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