Recently, the research team led by Professor Lian Qizhou from the Faculty of Synthetic Biology at Shenzhen University of Advanced Technology published important research findings in the international academic journalJournal of Advanced Research.The study elucidated the therapeutic mechanisms of human umbilical cord mesenchymal stem cells and their extracellular vesicles in treating Alport syndrome (hereditary nephritis), while also achieving important advances in clinical translation.

Alport syndrome is a hereditary kidney disease caused by mutations in theCOL4A5gene. Patients often present with persistent proteinuria and hematuria in childhood. In male patients, the disease progresses rapidly, often developing into end-stage renal disease before the age of 30. No curative treatment is currently available, and clinical treatment relies heavily on dialysis or kidney transplantation. In response to the limited therapeutic options available for this disease, Professor Lian Qizhou and his team explored novel therapeutic strategies.

Exploring the Renal Protective Mechanisms of Stem Cells and Extracellular Vesicles

The study employed a Col4a5 mutant mouse model that closely recapitulates the pathological features of the human disease to systematically evaluate the therapeutic potential of human umbilical cord mesenchymal stem cells and their secreted extracellular vesicles. The experimental results showed that after intravenous infusion treatment, the proteinuria level in the model mice was significantly reduced, renal inflammation, fibrosis, and glomerulosclerosis were significantly alleviated, and overall survival was prolonged by approximately 9 weeks.

At the mechanistic level, the research team integrated multi-omics approaches with in vitro cellular experiments and identified miR-146a-5p, enriched in mesenchymal stem cell-derived extracellular vesicles, as a critical regulatory factor in the therapeutic process. Specifically, this molecule functions as a key signaling mediator within extracellular vesicles. Acting as a molecular “brake”, miR-146a-5p suppresses NF-κB-mediated inflammatory signaling and promotes macrophage polarization toward an anti-inflammatory phenotype, thereby mitigating renal inflammation and fibrotic progression. Particularly noteworthy is that the preliminary application of this treatment regimen in the pediatric patient has demonstrated favorable tolerability and safety profiles, laying the groundwork for future clinical investigations.

Validating the “Cell-Free” Strategy Provides Scientific Basis for “Off-the-Shelf” Therapies

This study not only elucidates the mechanism of stem cell therapy for hereditary kidney disease but also demonstrates the feasibility of the “cell-free” treatment strategy based on extracellular vesicles at the application level. Compared with traditional cell therapy, extracellular vesicles show significant advantages in product stability, storage and transportation, and large-scale production, providing a strong scientific foundation for the development of standardized “off-the-shelf” therapeutic products.

Looking ahead, this study opens up new therapeutic avenues for the treatment of hereditary kidney disease. The extracellular vesicle-based treatment strategy has the characteristics of standardized manufacturing processes, feasible quality control, and long-term storage, and holds strong potential for development into standardized off-the-shelf therapeutics. This innovative therapy is expected to provide patients with more convenient treatment options while reducing treatment costs and enhancing treatment accessibility. The research team will subsequently conduct larger-scale preclinical evaluations and follow clinical research norms to further evaluate its efficacy and safety in broader patient populations, accelerating its translation from bench to bedside.

Professor Lian Qizhou, Distinguished Professor at the Faculty of Synthetic Biology, Shenzhen University of Advanced Technology, and Professor Ren Lijie from the First Affiliated Hospital of Shenzhen University are the co-corresponding authors. Dr. Huang Li, Visiting Scholar at the Faculty of Synthetic Biology, Shenzhen University of Advanced Technology, is the first author. The research was completed by core units including the Faculty of Synthetic Biology at Shenzhen University of Advanced Technology and the State Key Laboratory of Quantitative Synthetic Biology, and was supported by projects such as the National Key R&D Program of the Ministry of Science and Technology and the Shenzhen Science and Technology Innovation Commission.

Link:https://www.sciencedirect.com/science/article/pii/S2090123226003048?via%3Dihub=