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

Area of Science:

• Stem Cell Biology
• Regenerative Medicine
• Immunology

Background:

• Multiple organ dysfunction syndrome (MODS) is a leading cause of death with limited therapeutic options.
• Mesenchymal stem cells (MSCs) show therapeutic potential, but inconsistent outcomes necessitate potent, standardized products.
• Highly active UC-derived MSCs (HA-UCMSCs) were developed with enhanced reparative capacity for improved efficacy.

Purpose of the Study:

• To evaluate the efficacy of HA-UCMSCs in a novel tree shrew model of MODS.
• To investigate the underlying mechanisms of HA-UCMSC therapeutic action in MODS.
• To identify potential serum biomarkers for MODS progression and treatment response.

Main Methods:

• MODS was induced in tree shrews via hemorrhagic shock, simulated infection, and compression.
• HA-UCMSCs were characterized for proliferation, differentiation, and surface marker expression.
• Therapeutic efficacy was assessed using hematological, biochemical, histopathological, and proteomic analyses (DIA-MS).

Main Results:

• HA-UCMSCs demonstrated superior proliferative capacity and ESC marker expression compared to conventional UCMSCs.
• In vivo, HA-UCMSCs localized to injured organs, reduced systemic inflammation, promoted tissue regeneration, and maintained homeostasis.
• Treatment with HA-UCMSCs significantly decreased MODS-related mortality and long-term disability.

Conclusions:

• A clinically relevant tree shrew model for MODS was established.
• HA-UCMSCs exhibit multi-organ protective effects and represent a promising therapy for MODS.
• Novel serum protein biomarkers associated with MODS and HA-UCMSC treatment were identified.