HA-UCMSCs as an innovative therapy for treating multiple organ dysfunction syndrome

BACKGROUND: Multiple organ dysfunction syndrome (MODS) is highly lethal and lacks effective therapies. Umbilical cord-derived mesenchymal stem cells (UCMSCs) regulate immunity, suppress inflammation, and promote tissue repair, suggesting potential benefit for MODS. However, despite over 1400 MSC-related clinical studies worldwide, inconsistent outcomes reflect the lack of potent, standardized products. Our group established highly active UCMSCs (HA-UCMSCs) with enhanced proliferative and reparative capacity. This study evaluated their efficacy in MODS and explored underlying mechanisms. METHODS: MODS was induced in tree shrews by combining hemorrhagic shock, simulated infection, and hind limb compression. HA-UCMSCs were isolated, expanded, and characterized for their nuclear-to-cytoplasmic ratio, proliferation rate, multilineage differentiation capacity, and expression of mesenchymal and embryonic stem cell surface markers. After intravenous infusion, therapeutic efficacy was assessed via hematological and biochemical parameters, histopathological analysis, and serum proteomics using data-independent acquisition (DIA) mass spectrometry. RESULTS: HA-UCMSCs exhibited enhanced biological features compared to conventional UCMSCs, including high proliferative capacity and ESC marker expression. In vivo, HA-UCMSCs homed to injured organs, alleviated systemic inflammation, facilitated tissue regeneration, and maintained hematopoietic homeostasis. Treatment significantly reduced mortality and long-term disability in MODS. DIA proteomic analysis identified 18 candidate serum proteins associated with disease progression and treatment efficacy. CONCLUSION: This study introduces a clinically relevant tree shrew model of MODS and demonstrates the multi-organ protective effects of HA-UCMSCs. These findings highlight HA-UCMSCs as a promising stem cell-based therapy for MODS and propose novel serum biomarkers for treatment monitoring.