Effect of astragaloside IV on the immunoregulatory function of adipose-derived mesenchymal stem cells from patients with psoriasis vulgaris

Abstract

Objective: To compare the phenotype and adipogenic and osteogenic differentiation capacities of adipose-derived mesenchymal stem cells (AMSCs) isolated from patients with psoriasis vulgaris and healthy donors, and to explore the effects of astragaloside IV, a Traditional Chinese Medicine, on the immunoregulatory function of AMSCs.

Methods: AMSCs were isolated from human adipose tissue and cultured for three generations in vitro. Cell phenotype and cell cycle analysis were performed by flow cytometry. Adipogenic and osteogenic differentiation of AMSCs was examined by lipid (oil red O) and alkaline phosphatase staining, respectively. Expression of inflammatory mediators was examined by real-time quantitative polymerase chain reaction analysis, and proliferation was quantified using the cell counting kit-8 assay.

Results: Expression of CD29, CD44, and CD73 was higher in AMSCs from healthy donors than psoriasis patients, while the reverse was true for expression of CD45, CD31, and HLA-DR. AMSCs from psoriasis patients had a greater ability to undergo adipogenic differentiation than cells from healthy donors, whereas there was no significant difference in osteogenic differentiation between AMSCs from the two sources. Compared with AMSCs from healthy donors, psoriasis patient-derived AMSCs expressed lower levels of the anti-inflammatory cytokines interleukin-10 and trans-forming growth factor-β (TGF-β) and the immune checkpoint ligand programmed cell death 1 ligand 1 (PD-L1) (P < 0.05) and higher levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Incubation of AMSCs from psoriasis patients with astragaloside IV had no significant effect on pro-liferation but increased the expression of TGF-β and PD-L1 and decreased the expression of IFN-γ and TNF-α.

Conclusion: AMSCs from patients with psoriasis vulgaris display abnormal proliferation and adipogenesis and an enhanced pro-inflammatory phenotype. These defects were normalized by treatment with astragaloside IV, suggesting that this Traditional Chinese Medicine may be useful for restoring the immunoregulatory function of AMSCs and immune homeostasis in patients with psoriasis vulgaris.

Keywords: adipogenesis; astragaloside IV; cell proliferation; immune regulation; mesenchymal stem cells; osteogenesis; psoriasis.

Figure 1. Cell cycle analysis of AMSCs from psoriasis patients and healthy donors

A: flow cytometric analysis of propidium iodide-stained third-generation AMSCs (adipose-derived mesenchymal stem cells) derived from healthy donors; B: flow cytometric analysis of propidium iodide-stained third-generation AMSCs derived from psoriasis patients; C: quantification of AMSCs of healthy donors and psoriasis patients in the indicated cell cycle stages. AMSCs: adipose-derived mesenchymal stem cells. Compared with the healthy donors AMSCs, ^aP < 0.05.

Figure 2. Induction of adipogenic and osteogenic differentiation in cultured AMSCs

A, C: third generation AMSCs from psoriasis patients; B, D: third generation AMSCs from healthy donors. A, B: induction of adipogenic differentiation of AMSCs by Oil Red O staining on day 13 (× 20); C, D: induction of osteogenic differentiation of AMSCs by alkaline phosphatase staining on day 6 (× 20). AMSCs: adipose-derived mesenchymal stem cells.