In situ licensing of mesenchymal stem cell immunomodulatory function via BMP-2 induced developmental process

• 成果类型: Article
• 署名作者: Zhu, Fuwei; Ji, Luli; Dai, Kai; Deng, Shunshu; Wang, Jing; Liu, Changsheng
• 署名单位: East China University of Science & Technology; East China University of Science & Technology; East China University of Science & Technology; East China University of Science & Technology
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14360
• DOI: 10.1073/pnas.2410579121
• 发表日期: 2024-11-26
• 关键词: mhc class-ii; stromal cells; ifn-gamma; trophoblast cells; prostaglandin e-2; interferon-gamma; dna methylation; expression; macrophages; mice

摘要

The immunomodulatory function of mesenchymal stem cells (MSCs) is plastic and susceptible to resident microenvironment in vivo or inflammatory factors in vitro. We propose a unique method to enhance the immunoregulatory functions of mesenchymal stem cells (MSCs) through an artificially controllable in vivo inflammatory microenvironment generated by biomaterials loaded with BMP-2 that induce bone development. MSCs activated through this method effectively induce M1 macrophage polarization toward the M2 phenotype, promote differentiation of na & iuml;ve T cells into regulatory T cells, and inhibit the proliferation of activated T cells via prostaglandin E2 (PGE2) secretion. This in vivo licensing not only preserves the immunogenicity of MSCs but also alters DNA methylation patterns, enabling MSCs to exhibit immunoregulatory effects with epigenetic memory. Validation in a mouse colitis model demonstrated their therapeutic efficacy and long- term viability. Furthermore, we found that the material composition influences the inflammatory response during development, with polysaccharide- based biomaterials proving advantageous over protein- based materials in establishing an inflammatory niche conducive to MSC activity. These findings underscore the potential of tissue engineering to create in vivo environments that license MSCs, offering a strategic avenue to enhance MSC- based therapies for addressing significant immune disorders.