Astragalus Polysaccharides Augment BMSCs Homing via SDF-1/CXCR4 Modulation: A Novel Approach to Counteract Peritoneal Mesenchymal Transformation and Fibrosis

Abstract

Purpose This study aims to investigate whether pretreatment with bone marrow mesenchymal stromal cells (BMSCs) and Astragalus polysaccharide (APS) can enhance their capacity to engraft in the peritoneum after in vitro transplantation, thereby strengthening the anti-fibrotic effect of BMSCs and elucidating the possible mechanisms involved. Methods Forty male SD rats were randomly divided into the control, PDF, PDF + BMSCs and PDF + APSBMSCs group, to establish rat peritoneal fibrosis models. The homing and anti-fibrotic effects of fluorescently labeled BMSCs and APS-BMSCs were studied. Stromal cell-derived factor-1 (SDF-1) levels were evaluated using ELISA, and the expression of CXCR4 (chemokine receptor type 4) in BMSCs following APS intervention was assessed using PCR and immunofluorescence staining. The effects of APS on BMSC migration and its role in the SDF-1/CXCR4 axis were investigated through Transwell migration assays and the CXCR4 antagonist AMD3100. Results In vivo and in vitro experiments confirmed that APS can promote the targeted homing of BMSCs to the peritoneum of PDF-induced rats, enhance the therapeutic effect, and increase the expression of CXCR4 in BMSCs. PDF-induced peritoneal and serum SDF-1 levels were significantly increased, promoting the homing of CXCR4-expressing BMSCs. Blocking the SDF-1/CXCR4 axis with AMD3100 reduced the migration of BMSCs, further weakening the therapeutic effect on peritoneal mesenchyme-to-mesothelial transition (MMT). APS upregulated the expression of CXCR4 in BMSCs, enhanced the activation of downstream pathways in the SDF-1/CXCR4 axis, and partially reversed the effects of AMD3100. Conclusion APS enhances the activation of downstream pathways in the SDF-1/CXCR4 axis by upregulating the expression of CXCR4 in BMSCs, promoting the targeted homing of BMSCs in peritoneal tissue, and enhancing its inhibitory effect on MMT and improvement of peritoneal fibrosis.