Engineered Stem Cell Booster Breaks Pathological Barriers to Treat Chronic Pancreatitis.

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.