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Remodeled CD146+CD271+ Bone Marrow Mesenchymal Stem Cells from Patients with Polycythemia Vera Exhibit Altered Hematopoietic Supportive Activity

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Abstract

An essential component of the hematopoietic microenvironment, bone marrow mesenchymal stem cells (BM-MSCs) play an important role in the homeostasis and pathogenesis of the hematopoietic system by regulating the fate of hematopoietic stem cells (HSCs). Previous studies revealed that BM-MSCs were functionally remodeled by malignant cells in leukemia. However, the alterations in BM-MSCs in polycythemia vera (PV) and their effects on HSCs still need to be elucidated. Our results demonstrated that although BM-MSCs from PV patients shared similar surface markers with those from healthy donors, they exhibited enhanced proliferation, decreased senescence, and abnormal osteogenic differentiation capacities. The CD146+CD271+ BM-MSC subpopulation, which is considered to give rise to typical cultured BM-MSCs and form bone and the hematopoietic stroma, was then sorted. Compared with those from healthy donors, CD146+CD271+ BM-MSCs from PV patients showed an impaired mesensphere formation capacity and abnormal differentiation toward osteogenic lineages. In addition, CD146+CD271+ PV BM-MSCs showed altered hematopoietic supportive activity when cocultured with cord blood CD34+ cells. Our study suggested that remodeled CD146+CD271+ BM-MSCs might contribute to the pathogenesis of PV, a finding that will shed light on potential therapeutic strategies for PV.

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Data availability

The accession number for the RNA-seq data reported in this paper is NCBI Gene Expression Omnibus (GEO) GSE87806.

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Funding

This work was supported by National Natural Science Foundation of China (81970120, 81890990), National Key Research and Development Program of China (2020YFE0203000) and CAMS Innovation Fund for Medical Sciences (2017-I2M-3–018).

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  1. Chao Chen and Mingying Zhang contributed equally.

Authors and Affiliations

  1. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China

    Chao Chen, Mingying Zhang, Rong Li, Jiajia Yuan, Wen Xing & Yuan Zhou

  2. Central Laboratory, Liaocheng People’s Hospital and Liaocheng School of Clinical Medicine, Shandong First Medical University, Liaocheng, 252000, Shandong, China

    Chao Chen

  3. Department of Pathology, Liaocheng People’s Hospital and Liaocheng School of Clinical Medicine, Shandong First Medical University, Liaocheng, 252000, Shandong, China

    Jinqiang Yan

  4. Department of Hematology, The Second Affiliated Hospital of Tianjin Medical University, Tianjin, 300211, China

    Yuhui Zhang & Jie Bai

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  1. Chao Chen
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Contributions

Chao Chen, Rong Li and Yuan Zhou designed the study. Chao Chen, Mingying Zhang and Rong Li performed the experiments. Chao Chen and Mingying Zhang performed RNA-Seq analysis. Jiajia Yuan, Jinqiang Yan, Yuhui Zhang, Wen Xing, Jie Bai and Yuan Zhou discussed and analyzed the data. Chao Chen, Mingying Zhang and Yuan Zhou wrote the manuscript. All authors reviewed, edited, and approved the manuscript.

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Correspondence to Jie Bai or Yuan Zhou.

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This study was approved by the Ethics Committee of Institute of Hematology, and Blood Diseases Hospital, Chinese Academy of Medical Sciences, according to the 1975 Declaration of Helsinki and its later ethical standards. Written informed consent was obtained from all participants included in this study.

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Chen, C., Zhang, M., Li, R. et al. Remodeled CD146+CD271+ Bone Marrow Mesenchymal Stem Cells from Patients with Polycythemia Vera Exhibit Altered Hematopoietic Supportive Activity. Stem Cell Rev and Rep 19, 406–416 (2023). https://doi.org/10.1007/s12015-022-10427-8

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