Wen Li, PhD | Chinese Academy of Medical Sciences; Tianjiao Wang, PhD; Xueping Li, PhD; Lu Zhang, PhD; Baohui Yuan, PhD; Yi Li, MS; Xuya Yu, MS
Competition Sponsor: Chinese Academy of Medical Sciences
Awardee Year: 2025
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder characterized by aberrant activation of the immune system. Current therapeutic regimens can partially alleviate symptoms and slow joint damage but rarely achieve complete remission or effectively restore immune homeostasis, and long-term administration is often limited by significant adverse effects. In this project, we propose the development of a novel biomimetic engineered stem cell nanovesicle platform that integrates dual immunoregulatory and microenvironment-remodeling functions. Specifically, mesenchymal stem cell (MSC)-derived nanovesicles will be genetically engineered to overexpress programmed death-ligand 1 (PD-L1), leveraging both their inherent immunomodulatory activity and immune checkpoint signaling to selectively suppress overactivated pathogenic T cells, modulate aberrant immune responses, prevent immune-mediated tissue damage, and restore immune tolerance. In parallel, catalytically active nanoclusters with multi-enzyme mimetic functions will be anchored onto the vesicle surface via stimulus-responsive linkers to selectively scavenge excessive reactive oxygen species (ROS) within inflamed tissues, thereby disrupting the pathological immune–oxidative stress feedback loop at its source. Animal studies demonstrate that this platform markedly attenuates joint inflammation, preserves cartilage and tissue architecture, and restores the Th17/Treg balance, ultimately maintaining immune homeostasis and tissue function. By integrating genetic engineering and chemical engineering approaches, this work establishes a novel stem cell nanovesicle system with synergistic immune reprogramming and microenvironment remodeling capabilities. This strategy offers a promising avenue for precise intervention in autoimmune diseases that severely threaten human health, holding substantial scientific significance and societal value in extending healthy lifespan and reducing disability rates.