Alteration in the Cytokine Secretion of Bone Marrow Stromal Cells from Patients with Chronic Myelomonocytic Leukemia Contribute to Impaired Hematopoietic Supportive Activity
Bone marrow stromal cells (BMSCs) represent an important cellular component of the bone marrow microenvironment, which play an important role in supporting and regulating the proliferation and differentiation of hematopoietic stem/progenitor cells (HSPCs). We have previously reported that the abilit...
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2018-01-01
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Series: | Stem Cells International |
Online Access: | http://dx.doi.org/10.1155/2018/5921392 |
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author | Hui Shi Yingshao Wang Rong Li Wen Xing Feng-Chun Yang Jie Bai Yuan Zhou |
author_facet | Hui Shi Yingshao Wang Rong Li Wen Xing Feng-Chun Yang Jie Bai Yuan Zhou |
author_sort | Hui Shi |
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description | Bone marrow stromal cells (BMSCs) represent an important cellular component of the bone marrow microenvironment, which play an important role in supporting and regulating the proliferation and differentiation of hematopoietic stem/progenitor cells (HSPCs). We have previously reported that the ability of BMSCs derived from CMML patients (CMML-BMSCs) in supporting the expansion of cord blood (CB) CD34+ cells was significantly reduced compared to BMSCs derived from healthy donors (HD-BMSCs). In addition, CMML-BMSCs led to a skewed differentiation of CB CD34+ cells favoring myeloid lineage compared with HD-BMSCs. To assess whether the altered cytokine secretion was one of the mechanisms to mediate the impaired hematopoietic supportive activity of CMML-BMSCs, a transwell coculture followed by cytokine array was performed. We showed that noncontacted coculture with CMML-BMSCs preferentially promoted the differentiation of CB CD34+ cells toward myeloid lineage. The expression levels of multiple cytokines (IL-6, IL-8, and GRO-β) were markedly reduced in CMML-BMSCs compared with HD-BMSCs. By supplementing IL-6, IL-8, or GRO-β, the hematopoietic supportive activity of CMML-BMSCs was partially restored. These results suggested that BMSCs may contribute to the pathogenesis of CMML by altering their cytokine secretion, which will shed light on the further investigation to develop novel therapeutic strategies for CMML patients. |
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institution | Kabale University |
issn | 1687-966X 1687-9678 |
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spelling | doaj-art-f9e40a3db6404df2b37415766cf69d572025-02-03T01:02:40ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/59213925921392Alteration in the Cytokine Secretion of Bone Marrow Stromal Cells from Patients with Chronic Myelomonocytic Leukemia Contribute to Impaired Hematopoietic Supportive ActivityHui Shi0Yingshao Wang1Rong Li2Wen Xing3Feng-Chun Yang4Jie Bai5Yuan Zhou6State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaDepartment of Biochemistry and Molecular Biology, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USAState Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaBone marrow stromal cells (BMSCs) represent an important cellular component of the bone marrow microenvironment, which play an important role in supporting and regulating the proliferation and differentiation of hematopoietic stem/progenitor cells (HSPCs). We have previously reported that the ability of BMSCs derived from CMML patients (CMML-BMSCs) in supporting the expansion of cord blood (CB) CD34+ cells was significantly reduced compared to BMSCs derived from healthy donors (HD-BMSCs). In addition, CMML-BMSCs led to a skewed differentiation of CB CD34+ cells favoring myeloid lineage compared with HD-BMSCs. To assess whether the altered cytokine secretion was one of the mechanisms to mediate the impaired hematopoietic supportive activity of CMML-BMSCs, a transwell coculture followed by cytokine array was performed. We showed that noncontacted coculture with CMML-BMSCs preferentially promoted the differentiation of CB CD34+ cells toward myeloid lineage. The expression levels of multiple cytokines (IL-6, IL-8, and GRO-β) were markedly reduced in CMML-BMSCs compared with HD-BMSCs. By supplementing IL-6, IL-8, or GRO-β, the hematopoietic supportive activity of CMML-BMSCs was partially restored. These results suggested that BMSCs may contribute to the pathogenesis of CMML by altering their cytokine secretion, which will shed light on the further investigation to develop novel therapeutic strategies for CMML patients.http://dx.doi.org/10.1155/2018/5921392 |
spellingShingle | Hui Shi Yingshao Wang Rong Li Wen Xing Feng-Chun Yang Jie Bai Yuan Zhou Alteration in the Cytokine Secretion of Bone Marrow Stromal Cells from Patients with Chronic Myelomonocytic Leukemia Contribute to Impaired Hematopoietic Supportive Activity Stem Cells International |
title | Alteration in the Cytokine Secretion of Bone Marrow Stromal Cells from Patients with Chronic Myelomonocytic Leukemia Contribute to Impaired Hematopoietic Supportive Activity |
title_full | Alteration in the Cytokine Secretion of Bone Marrow Stromal Cells from Patients with Chronic Myelomonocytic Leukemia Contribute to Impaired Hematopoietic Supportive Activity |
title_fullStr | Alteration in the Cytokine Secretion of Bone Marrow Stromal Cells from Patients with Chronic Myelomonocytic Leukemia Contribute to Impaired Hematopoietic Supportive Activity |
title_full_unstemmed | Alteration in the Cytokine Secretion of Bone Marrow Stromal Cells from Patients with Chronic Myelomonocytic Leukemia Contribute to Impaired Hematopoietic Supportive Activity |
title_short | Alteration in the Cytokine Secretion of Bone Marrow Stromal Cells from Patients with Chronic Myelomonocytic Leukemia Contribute to Impaired Hematopoietic Supportive Activity |
title_sort | alteration in the cytokine secretion of bone marrow stromal cells from patients with chronic myelomonocytic leukemia contribute to impaired hematopoietic supportive activity |
url | http://dx.doi.org/10.1155/2018/5921392 |
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