hPMSCs prevent erythrocytes dysfunction caused by graft versus host disease via promoting GSH synthesis

• Published in: International immunopharmacology 2024-09, Vol.139, p.112689, Article 112689
• Main Authors: Xiong, Yanlian, Wang, Feifei, Mu, Huanmei, Zhang, Aiping, Zhao, Yaxuan, Han, Kaiyue, Zhang, Jiashen, Zhang, Hengchao, Wang, Zhuoya, Ma, Junjie, Wei, Rongxia, Luan, Xiying
• Format: Article
• Language: English
• Subjects: Adult; Animals; Cells, Cultured; Disease Models, Animal; Erythrocyte Deformability; Erythrocytes; Erythrocytes - metabolism; Female; Glutathione - metabolism; Graft vs Host Disease; GSH; GVHD; Hematopoietic Stem Cell Transplantation - adverse effects; hPMSCs; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells - metabolism; Mice; Mice, Inbred BALB C; Middle Aged; Oxidative Stress; Placenta - metabolism; Pregnancy
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.112689

•hPMSCs alleviate the oxidative stress of RBCs in GVHD mice.•hPMSCs improve the antioxidant capacity of RBCs in GVHD mice.•hPMSCs promote GSH synthesis of RBCs in GVHD mice. Oxidative stress is increased in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients and leads to the development of graft versus host disease (GVHD). Mesenchymal stromal cells (MSCs) can ameliorate GVHD by regulating the function of T cells. However, whether MSCs can modulate erythrocyte antioxidant metabolism and thus reduce GVHD is not known. Forty female BALB/c mice were randomly assigned to four groups: the control, GVHDhigh, hPMSC, and PBS groups. A hypoxanthine/xanthine oxidase system was used to steadily and gradually produce superoxide in an in vitro experiment. A scanning microscope was used to examine the ultrastructure of erythrocytes. Laser diffraction analyses were used to analyze erythrocyte deformability. Western blotting was used to measure the expression of the erythrocyte membrane skeleton proteins Band 3 and β-Spectrin. Corresponding kits were used to assess the levels of oxidative damage and the activity of antioxidant enzymes. Morphological and deformability defects were significantly increased in erythrocytes from GVHD patients. Band 3 and β-Spectrin expression was also reduced in GVHD patients and model mice. Furthermore, we observed significantly increased oxidative stress-induce injury and decreased antioxidant capability in erythrocytes from both GVHD patients and model mice. Subsequent research showed that human placenta-derived MSC (hPMSC) therapy decreased the GVHD-induced redox imbalance in erythrocytes. Furthermore, our findings suggested that upregulating glucose metabolism promoted both the de novo synthesis and recycling of GSH, which is the primary mechanism by which hPMSCs mediate the increase in antioxidant capacity in erythrocytes. Together, our findings suggest that hPMSCs can increase antioxidant capacity by increasing erythrocyte GSH production and thus ameliorate GVHD.