Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
J Biomed Sci. 2020 Sep 1;27(1):91. doi: 10.1186/s12929-020-00685-4.
Preconditioning before bone marrow transplantation such as irradiation causes vascular endothelial cells damage and promoting the repair of damaged endothelial cells is beneficial for hematopoietic reconstitution. Pigment epithelium-derived factor (PEDF) regulates vascular permeability. However, PEDF's role in the repair of damaged endothelial cells during preconditioning remains unclear. The purpose of our study is to investigate PEDF's effect on preconditioning-induced damage of endothelial cells and hematopoietic reconstitution.
Damaged endothelial cells induced by irradiation was co-cultured with hematopoietic stem cells (HSC) in the absence or presence of PEDF followed by analysis of HSC number, cell cycle, colony formation and differentiation. In addition, PEDF was injected into mice model of bone marrow transplantation followed by analysis of bone marrow injury, HSC number and peripheral hematopoietic reconstitution as well as the secretion of cytokines (SCF, TGF-β, IL-6 and TNF-α). Comparisons between two groups were performed by student t-test and multiple groups by one-way or two-way ANOVA.
Damaged endothelial cells reduced HSC expansion and colony formation, induced HSC cell cycle arrest and apoptosis and promoted HSC differentiation as well as decreased PEDF expression. Addition of PEDF increased CD144 expression in damaged endothelial cells and inhibited the increase of endothelial permeability, which were abolished after addition of PEDF receptor inhibitor Atglistatin. Additionally, PEDF ameliorated the inhibitory effect of damaged endothelial cells on HSC expansion in vitro. Finally, PEDF accelerated hematopoietic reconstitution after bone marrow transplantation in mice and promoted the secretion of SCF, TGF-β and IL-6.
PEDF inhibits the increased endothelial permeability induced by irradiation and reverse the inhibitory effect of injured endothelial cells on hematopoietic stem cells and promote hematopoietic reconstruction.
骨髓移植前的预处理如照射会导致血管内皮细胞损伤，促进受损内皮细胞的修复有利于造血重建。色素上皮衍生因子（PEDF）调节血管通透性。然而，PEDF 在预处理过程中对受损内皮细胞修复的作用尚不清楚。我们的研究目的是探讨 PEDF 对预处理诱导的内皮细胞损伤和造血重建的影响。
用照射损伤内皮细胞与造血干细胞（HSC）共培养，分析 HSC 数量、细胞周期、集落形成和分化。此外，将 PEDF 注射到骨髓移植小鼠模型中，分析骨髓损伤、HSC 数量和外周造血重建以及细胞因子（SCF、TGF-β、IL-6 和 TNF-α）的分泌。两组间比较采用学生 t 检验，多组间比较采用单因素或双因素方差分析。
损伤的内皮细胞减少了 HSC 的扩增和集落形成，诱导 HSC 细胞周期停滞和凋亡，并促进 HSC 分化，同时降低了 PEDF 的表达。添加 PEDF 增加了损伤内皮细胞中 CD144 的表达，并抑制了内皮通透性的增加，而添加 PEDF 受体抑制剂 Atglistatin 则消除了这种增加。此外，PEDF 改善了损伤内皮细胞对体外 HSC 扩增的抑制作用。最后，PEDF 加速了小鼠骨髓移植后的造血重建，并促进了 SCF、TGF-β 和 IL-6 的分泌。
PEDF 抑制照射引起的内皮通透性增加，逆转损伤内皮细胞对造血干细胞的抑制作用，促进造血重建。
