Engineering the Residence Time and Immune Cloaking of Mesenchymal Stromal Cells with Microgel-coating to Overcome Chronic Fibrotic Remodeling
발표자
조익성 (Kyushu University)
연구책임자
조익성 (Kyushu University)
공동저자
조익성 (Kyushu University)
초록
내용
Fibrotic lung disease has limited therapies, and delivered mesenchymal stromal cells (MSCs) are rapidly phagocytosed by alveolar macrophages. We encapsulated single MSCs in soft (~3 µm, ~2 kPa) RGD-alginate microgels bearing a CD47 agonist peptide (pCD47), combining a compliant niche with a “don’t-eat-me” signal. In bleomycin-injured mice with acute or chronic fibrosis, pCD47 increased MSC lung half-life from ~13 h to ~100 h via SIRPα, SIRPα blockade removed retention. One dose reduced collagen and improved lung mechanics, whereas unmodified gels were ineffective. scRNA-seq (>20,000 CD45⁺ cells) showed depletion of profibrotic Spp1hi alveolar macrophages and expansion of a Cd74hi MHC-IIhi antigen-presenting subset, MHC-II blockade prevented collagen resolution. Soft pCD47 microgels thus prolong MSC residence and reprogram macrophages to reverse established fibrosis. References: Cho et al., Advanced Materials (2025).