Dysfunctional bone marrow endothelial progenitor cells are involved in patients with myelodysplastic syndromes
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 a...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-03-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03354-2 |
| _version_ | 1811280211501645824 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Tong Xing |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T01:09:30Z |
| format | Article |
| id | doaj.art-0616e80e7f6d47c58bb61dd8c0c26ef3 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-13T01:09:30Z |
| publishDate | 2022-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-0616e80e7f6d47c58bb61dd8c0c26ef32022-12-22T03:09:11ZengBMCJournal of Translational Medicine1479-58762022-03-0120111710.1186/s12967-022-03354-2Dysfunctional bone marrow endothelial progenitor cells are involved in patients with myelodysplastic syndromesTong Xing0Zhong-Shi Lyu1Cai-Wen Duan2Hong-Yan Zhao3Shu-Qian Tang4Qi Wen5Yuan-Yuan Zhang6Meng Lv7Yu Wang8Lan-Ping Xu9Xiao-Hui Zhang10Xiao-Jun Huang11Yuan Kong12Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityKey Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai Children’s Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine and Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of MedicinePeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking UniversityAbstract 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.https://doi.org/10.1186/s12967-022-03354-2Myelodysplastic syndromesEndothelial progenitor cellsHaematopoiesisImmune regulation |
| spellingShingle | 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 Dysfunctional bone marrow endothelial progenitor cells are involved in patients with myelodysplastic syndromes Journal of Translational Medicine Myelodysplastic syndromes Endothelial progenitor cells Haematopoiesis Immune regulation |
| title | Dysfunctional bone marrow endothelial progenitor cells are involved in patients with myelodysplastic syndromes |
| title_full | Dysfunctional bone marrow endothelial progenitor cells are involved in patients with myelodysplastic syndromes |
| title_fullStr | Dysfunctional bone marrow endothelial progenitor cells are involved in patients with myelodysplastic syndromes |
| title_full_unstemmed | Dysfunctional bone marrow endothelial progenitor cells are involved in patients with myelodysplastic syndromes |
| title_short | Dysfunctional bone marrow endothelial progenitor cells are involved in patients with myelodysplastic syndromes |
| title_sort | dysfunctional bone marrow endothelial progenitor cells are involved in patients with myelodysplastic syndromes |
| topic | Myelodysplastic syndromes Endothelial progenitor cells Haematopoiesis Immune regulation |
| url | https://doi.org/10.1186/s12967-022-03354-2 |
| work_keys_str_mv | AT tongxing dysfunctionalbonemarrowendothelialprogenitorcellsareinvolvedinpatientswithmyelodysplasticsyndromes AT zhongshilyu dysfunctionalbonemarrowendothelialprogenitorcellsareinvolvedinpatientswithmyelodysplasticsyndromes AT caiwenduan dysfunctionalbonemarrowendothelialprogenitorcellsareinvolvedinpatientswithmyelodysplasticsyndromes AT hongyanzhao dysfunctionalbonemarrowendothelialprogenitorcellsareinvolvedinpatientswithmyelodysplasticsyndromes AT shuqiantang dysfunctionalbonemarrowendothelialprogenitorcellsareinvolvedinpatientswithmyelodysplasticsyndromes AT qiwen dysfunctionalbonemarrowendothelialprogenitorcellsareinvolvedinpatientswithmyelodysplasticsyndromes AT yuanyuanzhang dysfunctionalbonemarrowendothelialprogenitorcellsareinvolvedinpatientswithmyelodysplasticsyndromes AT menglv dysfunctionalbonemarrowendothelialprogenitorcellsareinvolvedinpatientswithmyelodysplasticsyndromes AT yuwang dysfunctionalbonemarrowendothelialprogenitorcellsareinvolvedinpatientswithmyelodysplasticsyndromes AT lanpingxu dysfunctionalbonemarrowendothelialprogenitorcellsareinvolvedinpatientswithmyelodysplasticsyndromes AT xiaohuizhang dysfunctionalbonemarrowendothelialprogenitorcellsareinvolvedinpatientswithmyelodysplasticsyndromes AT xiaojunhuang dysfunctionalbonemarrowendothelialprogenitorcellsareinvolvedinpatientswithmyelodysplasticsyndromes AT yuankong dysfunctionalbonemarrowendothelialprogenitorcellsareinvolvedinpatientswithmyelodysplasticsyndromes |