Pharmacodynamic evaluation and mechanism study of cord blood nucleated cell extract in the treatment of rheumatoid arthritis

Abstract

Objective: To assess the effectiveness of cord blood nucleated cell extract (CBNCE) in rheumatoid arthritis (RA) and explore the mechanism preliminarily.

Methods: CBNCE injection was prepared by adding HClO₄ and KOH to cord blood. The efficacy of CBNCE was assessed through a lymphocyte proliferation assay. Subsequently, the CIA model was utilized as the RA model, with rats being randomly assigned to a normal group, model group, CBNCE group (1 mL/d), and HSS group (hydrocortisone sodium succinate, 0.2 mL/d). Following a 7-day period of immune system enhancement, continuous medication was administered for the subsequent 21 days. Foot swelling tests, HE staining, flow cytometry, ELISA, WB, and immunofluorescence were conducted.

Results: The average inhibitory rate of CBNCE on lymphocyte proliferation was 83.51%. Compared with the model group, rats in the CBNCE group showed a decrease of inflammatory cell infiltration in ankle tissue. The left hindfoot volume (days 5, 9, 10, and 12-21), Th17 percentage and Th17/Treg ratio in peripheral blood, and the levels of IL-1, IL-6, IL-8, and IL-17 in ankle effusion, as well as the MMP-3 protein expression in synovial tissue were significantly decreased (P < 0.05). There were significant (P < 0.05) increases in the fluorescence intensity of Aggrecan and Collagen type I, as well as in the amounts of IL-4 and IL-10.

Conclusion: CBNCE modulates the Th17/Treg balance by decreasing the Th17 cells, suppressing the secretion of IL-1, IL-6, IL-8, and IL-17, enhancing the secretion of IL-4 and IL-10, and further inhibiting the expression of MMP-3 protein, thereby increasing the level of Aggrecan and Collagen type I. Ultimately, CBNCE alleviates RA. Key Points • Our study was the first to explore the effect and mechanism of cord blood nucleated cell extract in the treatment of rheumatoid arthritis. • This study offers a theoretical foundation and introduces a novel concept for utilizing cord blood in the treatment of rheumatoid arthritis.

Keywords: Cord blood nucleated cell extract; Mechanism; Pharmacodynamic evaluation; Rheumatoid arthritis.