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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | Myelodysplastic Syndrome | Research

Dysfunctional bone marrow endothelial progenitor cells are involved in patients with myelodysplastic syndromes

Authors: Tong Xing, Zhong-Shi Lyu, Cai-Wen Duan, Hong-Yan Zhao, Shu-Qian Tang, Qi Wen, Yuan-Yuan Zhang, Meng Lv, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Xiao-Jun Huang, Yuan Kong

Published in: Journal of Translational Medicine | Issue 1/2022

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Abstract

Background

Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective haematopoiesis and immune deregulation. Emerging evidence has shown the effect of bone marrow (BM) endothelial progenitor cells (EPCs) in regulating haematopoiesis and immune balance. However, the number and functions of BM EPCs in patients with different stages of MDS remain largely unknown.

Methods

Patients with MDS (N = 30), de novo acute myeloid leukaemia (AML) (N = 15), and healthy donors (HDs) (N = 15) were enrolled. MDS patients were divided into lower-risk MDS (N = 15) and higher-risk MDS (N = 15) groups according to the dichotomization of the Revised International Prognostic Scoring System. Flow cytometry was performed to analyse the number of BM EPCs. Tube formation and migration assays were performed to evaluate the functions of BM EPCs. In order to assess the gene expression profiles of BM EPCs, RNA sequencing (RNA-seq) were performed. BM EPC supporting abilities of haematopoietic stem cells (HSCs), leukaemia cells and T cells were assessed by in vitro coculture experiments.

Results

Increased but dysfunctional BM EPCs were found in MDS patients compared with HDs, especially in patients with higher-risk MDS. RNA-seq indicated the progressive change and differences of haematopoiesis- and immune-related pathways and genes in MDS BM EPCs. In vitro coculture experiments verified that BM EPCs from HDs, lower-risk MDS, and higher-risk MDS to AML exhibited a progressively decreased ability to support HSCs, manifested as elevated apoptosis rates and intracellular reactive oxygen species (ROS) levels and decreased colony-forming unit plating efficiencies of HSCs. Moreover, BM EPCs from higher-risk MDS patients demonstrated an increased ability to support leukaemia cells, characterized by increased proliferation, leukaemia colony-forming unit plating efficiencies, decreased apoptosis rates and apoptosis-related genes. Furthermore, BM EPCs induced T cell differentiation towards more immune-tolerant cells in higher-risk MDS patients in vitro. In addition, the levels of intracellular ROS and the apoptosis ratios were increased in BM EPCs from MDS patients, especially in higher-risk MDS patients, which may be therapeutic candidates for MDS patients.

Conclusion

Our results suggest that dysfunctional BM EPCs are involved in MDS patients, which indicates that improving haematopoiesis supporting ability and immuneregulation ability of BM EPCs may represent a promising therapeutic approach for MDS patients.
Appendix
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Metadata
Title
Dysfunctional bone marrow endothelial progenitor cells are involved in patients with myelodysplastic syndromes
Authors
Tong Xing
Zhong-Shi Lyu
Cai-Wen Duan
Hong-Yan Zhao
Shu-Qian Tang
Qi Wen
Yuan-Yuan Zhang
Meng Lv
Yu Wang
Lan-Ping Xu
Xiao-Hui Zhang
Xiao-Jun Huang
Yuan Kong
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03354-2

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