PG2, a botanically derived drug extracted from Astragalus membranaceus, promotes proliferation and immunosuppression of umbilical cord-derived mesenchymal stem cells

Abstract

Ethnopharmacological relevance: Astragalus membranaceus is used to manage the deficiency of vital energy in traditional Chinese medicine and confirmed to have many biological functions. Mesenchymal stem cells (MSCs) possess immunosuppressive effects, and are widely used for regenerative medicine and immune disorders.

Aims of study: This study investigated the effects of Astragalus polysaccharides (APS) on umbilical cord-derived MSCs (UCMSCs), including morphology, surface marker expression, proliferation, differentiation, and in-vitro and in-vivo immunosuppressive capacities.

Materials and methods: MSCs isolated from umbilical cords were used. PG2 injection, a botanically derived drug containing a mixture of APS, was added into the culture medium to prepare PG2-treated UCMSCs. The morphology, surface marker expression, proliferation, and differentiation of UCMSCs were determined. The in-vitro immunosuppressive effects of UCMSCs were examined by peripheral blood mononuclear cell (PBMC) proliferation assay. The in-vivo effects were evaluated by circulatory inflammation-associated cytokine levels in mice with septic peritonitis induced by cecal ligation and puncture (CLP) operation.

Results: Compared with control UCMSCs, UCMSCs had higher population doublings when exposed to PG2-containing medium (P = 0.003). The reduction rates of PBMC proliferation after phytohemagglutinin stimulation increased significantly when UCMSCs were treated with PG2 (P = 0.004). The serum levels of inflammation-associated cytokines, including TNF-α, IL-6, MCP-1, IFN-γ, and IL-1β, were significantly lower at 6h after CLP in the mice receiving PG2-treated UCMSCs.

Conclusions: Our results demonstrated that PG2 can enhance UCMSC proliferation and their in-vitro and in-vivo immunosuppressive effects. Consequently, UCMSCs can be obtained in earlier passages to avoid senescence, and sufficient cells can be acquired faster for clinical use. With stronger immunosuppressive effects, UCMSCs may treat immune disorders more effectively. Further studies are warranted.

Keywords: Astragalus polysaccharides; Immunosuppression; Mesenchymal stem cells; PG2; Proliferation.