2. Academic Validation
  3. PEDF promotes the repair of bone marrow endothelial cell injury and accelerates hematopoietic reconstruction after bone marrow transplantation

PEDF promotes the repair of bone marrow endothelial cell injury and accelerates hematopoietic reconstruction after bone marrow transplantation

  • J Biomed Sci. 2020 Sep 1;27(1):91. doi: 10.1186/s12929-020-00685-4.
Wen Ju 1 2 3,  Wenyi Lu 1 2 3,  Lan Ding 1 2 3,  Yurong Bao 1 2 3,  Fei Hong 1 2 3,  Yuting Chen 1 2 3,  Hui Gao 1 2 3,  Xiaoqi Xu 1 2 3,  Guozhang Wang 1 2 3,  Weiwei Wang 1 2 3,  Xi Zhang 4,  Chunling Fu 1 2 3,  Kunming Qi 1 2 3,  Zhenyu Li 2 3,  Kailin Xu 5 6,  Jianlin Qiao 7 8 9,  Lingyu Zeng 10 11 12
Affiliations

Affiliations

  • 1 Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.
  • 2 Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
  • 3 Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
  • 4 Medical Center of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
  • 5 Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China. lihmd@163.com.
  • 6 Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. lihmd@163.com.
  • 7 Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China. jianlin.qiao@gmail.com.
  • 8 Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China. jianlin.qiao@gmail.com.
  • 9 Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. jianlin.qiao@gmail.com.
  • 10 Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China. zengly2000@163.com.
  • 11 Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China. zengly2000@163.com.
  • 12 Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. zengly2000@163.com.
PMID: 32873283 DOI: 10.1186/s12929-020-00685-4
Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords

Endothelial cells; Hematopoietic reconstitution; Hematopoietic stem cells; PEDF.

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