Guangdong Provincial Key Laboratory of Proteomics and State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Molecules. 2021 Jun 3;26(11):3395. doi: 10.3390/molecules26113395.
Total body irradiation is a standard procedure of bone marrow transplantation (BMT) which causes a rapid increase in reactive oxygen species (ROS) in the bone marrow microenvironment during BMT. The increase in ROS reduces the engraftment ability of donor cells, thereby affecting the bone marrow recovery of recipients after BMT. In the early weeks following transplantation, recipients are at high risk of severe infection due to weakened hematopoiesis. Thus, it is imperative to improve engraftment capacity and accelerate bone marrow recovery in BMT recipients. In this study, we constructed recombinant copper/zinc superoxide dismutase 1 (SOD1) fused with the cell-penetrating peptide (CPP), the trans-activator of transcription (Tat), and showed that this fusion protein has penetrating ability and antioxidant activity in both RAW264.7 cells and bone marrow cells in vitro. Furthermore, irradiated mice transplanted with SOD1-Tat-treated total bone marrow donor cells showed an increase in total bone marrow engraftment capacity two weeks after transplantation. This study explored an innovative method for enhancing engraftment efficiency and highlights the potential of CPP-SOD1 in ROS manipulation during BMT.
全身放射治疗是骨髓移植（BMT）的标准程序，它会在 BMT 期间导致骨髓微环境中活性氧（ROS）的快速增加。ROS 的增加会降低供体细胞的植入能力，从而影响 BMT 后受者的骨髓恢复。在移植后的早期几周，由于造血功能减弱，受者极易受到严重感染的风险。因此，提高 BMT 受者的植入能力并加速骨髓恢复至关重要。在这项研究中，我们构建了与穿透肽（CPP）、转录激活因子（Tat）融合的重组铜/锌超氧化物歧化酶 1（SOD1），并表明该融合蛋白在 RAW264.7 细胞和骨髓细胞中均具有穿透能力和抗氧化活性。此外，用 SOD1-Tat 处理的全身骨髓供体细胞移植的照射小鼠在移植后两周显示出总骨髓植入能力的增加。这项研究探索了一种增强植入效率的创新方法，并强调了 CPP-SOD1 在 BMT 期间 ROS 操纵中的潜力。
