Background/Purpose:  Evidence has accumulated that umbilical cord (UC)-derived mesenchymal stem cells (MSCs) show therapeutic effects on systemic lupus erythematosus (SLE). Deficiency in SLE macrophages exhibits excessive activation and inefficient clearance of self nuclear antigens. In this study, we aim to investigate whether UC-MSCs could increase the immunomodulatory function and phagocytic activity of lupus macrophages.

Methods:  Blood samples were collected from 9 SLE patients, who fulfilled the SLE diagnostic criteria of American College of Rheumatology in 1999. All patients’ Systemic Lupus Erythematosus Disease Activity Indexes (SLEDAI) were above 8. CD14⁺ monocytes were isolated from peripheral blood of healthy donors (HCs) and SLE patients. We cultured human monocytes for 7 days with macrophage colony-stimulating factor (M-CSF) to generate macrophages, and then co-cultured them for 2 more days with/without UC-MSCs in transwell culture systems. CD4⁺ T cells isolated from HCs were co-cultured with/without prepared macrophages. After 4 days, the proliferation levels of T cells were detected by flow cytometry. To determine the phagocytic activity of macrophages, apoptotic neutrophils were added into the cultures for 2 hours. The uptake of apoptotic cells were determined by flow cytometry.

Results: Compared with HC macrophages, the immunomodulatory function of SLE macrophages was impaired. SLE macrophages were incapable of suppressing the proliferation of CD4⁺ T cells effectively. The phagocytic activity of SLE macrophages was also deficient in engulfment of apoptotic cells. Next, we determined the capacities of immunomodulatory and phagocytosis of SLE macrophages co-cultured with UC-MSCs in a transwell system. Flow cytometric analysis showed that SLE macrophages co-cultured with UC-MSCs significantly increased the abilities to suppress the CD4⁺ T cells proliferation and phagocytic activities to engulf apoptotic neutrophils compared with macrophages cultured alone.

Conclusion: Our results indicate that UC-MSCs promoted the immunomodulatory function and phagocytic activity of macrophages in SLE, providing a novel mechanism for MSC-therapeutic function for SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mesenchymal-stem-cells-ameliorate-the-deficiencies-in-immunomodulatory-and-phagocytic-capacities-of-lupus-macrophages/