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Archive > Volume 33 Issue 6 > 2026,33(6):589-601. DOI:10.3872/j.issn.1007-385X.2026.06.001 Prev Next
Mesenchymal stromal cell therapy for pancreatic ductal adenocarcinoma: mechanisms, applications, and challenges
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Abstract:
[Abstract] Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive, often diagnosed at late stages, and generally shows limited response to systemic therapies. The dense fibrotic stroma, abnormal vasculature, and immunosuppressive tumor microenvironment collectively impair drug penetration and contribute to the "cold tumor" phenotype, significantly limiting therapeutic efficacy. Mesenchymal stromal cells (MSCs), known for their inflammatory-directed migration, immune modulation, and paracrine effects, can serve as living delivery vehicles to selectively deliver cytokines, chemotherapeutic agents, oncolytic viruses, and suicide genes to tumor sites, offering promising strategies to overcome stromal barriers and reshape the tumor microenvironment. However, MSCs exhibit significant plasticity in the tumor context, displaying a "double-edged sword" effect, potentially being reprogrammed by the tumor microenvironment to exert immunosuppressive, pro-angiogenic, pro-fibrotic, pro-invasive, and drug-resistance-supporting activities. Moreover, the in vivo distribution and payload release of MSCs lack quantifiable and controllable evidence, while inconsistent manufacturing processes and functional quality control standards hinder clinical translation. This review focuses on the mechanisms underlying MSC-tumor microenvironment interactions and recent advances in engineered MSC-based delivery of therapeutic proteins, drugs, oncolytic viruses, and suicide genes, with particular emphasis on challenges related to safety, efficacy evaluation, and quality control. Developing programmable MSC platforms with microenvironment-responsive release and safety switches, establishing functional evaluation or release criteria for tumor therapy, and advancing cell-free approaches such as MSC-derived extracellular vesicles may enhance reproducibility and reduce risks associated with long-term persistence in vivo.
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