Engineered Stem Cell Booster Breaks Pathological Barriers to Treat Chronic Pancreatitis

Abstract Chronic pancreatitis (CP) is a long‐standing progressive fibrosis and has long been considered incurable, which remains a heavy health burden worldwide. Mesenchymal stem cells (MSCs) with anti‐fibrosis properties are currently used in the treatment of fibroinflammatory diseases. However, its therapeutic effect is limited mainly due to two main types of pathological barriers in CP: 1) Fibrotic collagen hinders cell delivery, and 2) Malignant microenvironment attacks cell inactivation. Here, a MSCs‐based exogenous nitric oxide (NO) delivery system (MSCs‐Lip@RNO) is constructed. In the MSCs‐Lip@RNO, NO not only can be a cell booster to regulate collagen fibers, relieve the vascular compression and enhance the accumulation of MSCs in the whole pancreas, but also can form a protective gas layer on the cell surface, which enhances the therapeutic effect of MSCs. In the CP rat model, the pancreatic injury and fibrosis are reduced with 7 days after a single dose administration of this long‐acting MSCs. Collectively, this study offers a promising strategy for enhancing the delivery and therapeutic efficacy of MSCs to break pathological barriers in CP treatment.