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Perivascular Cells and NADPH Oxidase Inhibition Partially Restore Hyperglycemia-Induced Alterations in Hematopoietic Stem Cell and Myeloid-Derived Suppressor Cell Populations in the Bone Marrow
BACKGROUND AND OBJECTIVES: Patients suffer from long-term diabetes can result in severe complications in multiple organs through induction of vascular dysfunctions. However, the effects of chronic hyperglycemic conditions on hematopoiesis and the microenvironment in the bone marrow (BM) are not yet...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Korean Society for Stem Cell Research
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457702/ https://www.ncbi.nlm.nih.gov/pubmed/30595009 http://dx.doi.org/10.15283/ijsc18097 |
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author | Kim, Ji-Young Lee, Ji Yoon Ha, Kwon-Soo Han, Eun-Taek Park, Won Sun Min, Chang-Ki Hong, Seok-Ho |
author_facet | Kim, Ji-Young Lee, Ji Yoon Ha, Kwon-Soo Han, Eun-Taek Park, Won Sun Min, Chang-Ki Hong, Seok-Ho |
author_sort | Kim, Ji-Young |
collection | PubMed |
description | BACKGROUND AND OBJECTIVES: Patients suffer from long-term diabetes can result in severe complications in multiple organs through induction of vascular dysfunctions. However, the effects of chronic hyperglycemic conditions on hematopoiesis and the microenvironment in the bone marrow (BM) are not yet well understood. METHODS: BM cells were harvested from femurs of mice and analyzed using flow cytometry. Human PVCs were cultured in serum-free α-MEM. After 24hrs, PVC-CM was collected and filtered through a 0.22 μm filter. RESULTS: In this study, we showed that hyperglycemia alters hematopoietic composition in the BM, which can partially be restored via paracrine mechanisms, including perivascular cells (PVCs) and NADPH oxidase (NOX) inhibition in mice with streptozotocin-induced diabetes. Prolonged hyperglycemic conditions resulted in an increase in the frequency and number of long-term hematopoietic stem cells as well as the number of total BM cells. The altered hematopoiesis in the BM was partially recovered by treatment with PVC-derived conditioned medium (CM). Long-term diabetes also increased the number of myeloid-derived suppressor cells in the BM, which was partially restored by the administration of PVC-CM and diphenyleneiodonium (DPI), a NOX inhibitor. We further showed the downregulation of ERK and p38 phosphorylation in BM cells of diabetic mice treated with PVC-CM and DPI. This may be associated with dysfunction of hematopoietic cells and promotion of subsequent diabetic complications. CONCLUSIONS: Our data suggested that alterations in BM hematopoietic composition due to prolonged hyperglycemic conditions might be restored by improvement of the hematopoietic microenvironment and modulation of NOX activity. |
format | Online Article Text |
id | pubmed-6457702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Korean Society for Stem Cell Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-64577022019-04-19 Perivascular Cells and NADPH Oxidase Inhibition Partially Restore Hyperglycemia-Induced Alterations in Hematopoietic Stem Cell and Myeloid-Derived Suppressor Cell Populations in the Bone Marrow Kim, Ji-Young Lee, Ji Yoon Ha, Kwon-Soo Han, Eun-Taek Park, Won Sun Min, Chang-Ki Hong, Seok-Ho Int J Stem Cells Original Article BACKGROUND AND OBJECTIVES: Patients suffer from long-term diabetes can result in severe complications in multiple organs through induction of vascular dysfunctions. However, the effects of chronic hyperglycemic conditions on hematopoiesis and the microenvironment in the bone marrow (BM) are not yet well understood. METHODS: BM cells were harvested from femurs of mice and analyzed using flow cytometry. Human PVCs were cultured in serum-free α-MEM. After 24hrs, PVC-CM was collected and filtered through a 0.22 μm filter. RESULTS: In this study, we showed that hyperglycemia alters hematopoietic composition in the BM, which can partially be restored via paracrine mechanisms, including perivascular cells (PVCs) and NADPH oxidase (NOX) inhibition in mice with streptozotocin-induced diabetes. Prolonged hyperglycemic conditions resulted in an increase in the frequency and number of long-term hematopoietic stem cells as well as the number of total BM cells. The altered hematopoiesis in the BM was partially recovered by treatment with PVC-derived conditioned medium (CM). Long-term diabetes also increased the number of myeloid-derived suppressor cells in the BM, which was partially restored by the administration of PVC-CM and diphenyleneiodonium (DPI), a NOX inhibitor. We further showed the downregulation of ERK and p38 phosphorylation in BM cells of diabetic mice treated with PVC-CM and DPI. This may be associated with dysfunction of hematopoietic cells and promotion of subsequent diabetic complications. CONCLUSIONS: Our data suggested that alterations in BM hematopoietic composition due to prolonged hyperglycemic conditions might be restored by improvement of the hematopoietic microenvironment and modulation of NOX activity. Korean Society for Stem Cell Research 2018-12-31 /pmc/articles/PMC6457702/ /pubmed/30595009 http://dx.doi.org/10.15283/ijsc18097 Text en Copyright © 2019 by the Korean Society for Stem Cell Research This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Kim, Ji-Young Lee, Ji Yoon Ha, Kwon-Soo Han, Eun-Taek Park, Won Sun Min, Chang-Ki Hong, Seok-Ho Perivascular Cells and NADPH Oxidase Inhibition Partially Restore Hyperglycemia-Induced Alterations in Hematopoietic Stem Cell and Myeloid-Derived Suppressor Cell Populations in the Bone Marrow |
title | Perivascular Cells and NADPH Oxidase Inhibition Partially Restore Hyperglycemia-Induced Alterations in Hematopoietic Stem Cell and Myeloid-Derived Suppressor Cell Populations in the Bone Marrow |
title_full | Perivascular Cells and NADPH Oxidase Inhibition Partially Restore Hyperglycemia-Induced Alterations in Hematopoietic Stem Cell and Myeloid-Derived Suppressor Cell Populations in the Bone Marrow |
title_fullStr | Perivascular Cells and NADPH Oxidase Inhibition Partially Restore Hyperglycemia-Induced Alterations in Hematopoietic Stem Cell and Myeloid-Derived Suppressor Cell Populations in the Bone Marrow |
title_full_unstemmed | Perivascular Cells and NADPH Oxidase Inhibition Partially Restore Hyperglycemia-Induced Alterations in Hematopoietic Stem Cell and Myeloid-Derived Suppressor Cell Populations in the Bone Marrow |
title_short | Perivascular Cells and NADPH Oxidase Inhibition Partially Restore Hyperglycemia-Induced Alterations in Hematopoietic Stem Cell and Myeloid-Derived Suppressor Cell Populations in the Bone Marrow |
title_sort | perivascular cells and nadph oxidase inhibition partially restore hyperglycemia-induced alterations in hematopoietic stem cell and myeloid-derived suppressor cell populations in the bone marrow |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457702/ https://www.ncbi.nlm.nih.gov/pubmed/30595009 http://dx.doi.org/10.15283/ijsc18097 |
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