Mesenchymal Stem Cells Derived and Cultured from Glioblastoma Multiforme Increase Tregs, Downregulate Th17, and Induce the Tolerogenic Phenotype of Monocyte-Derived Cells

Mesenchymal stem cells (MSCs) possess immunosuppressive properties and have been described in the tumor microenvironment of glioblastoma multiforme (GBM). This manuscript has two major topics—first, to describe isolated and cultured MSCs derived from GBM (GB-MSCs) and second, to examine their in vit...

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Main Authors: Kalina Tumangelova-Yuzeir, Emanuil Naydenov, Ekaterina Ivanova-Todorova, Ekaterina Krasimirova, Georgi Vasilev, Sevdalin Nachev, Dobroslav Kyurkchiev
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2019/6904638
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author Kalina Tumangelova-Yuzeir
Emanuil Naydenov
Ekaterina Ivanova-Todorova
Ekaterina Krasimirova
Georgi Vasilev
Sevdalin Nachev
Dobroslav Kyurkchiev
author_facet Kalina Tumangelova-Yuzeir
Emanuil Naydenov
Ekaterina Ivanova-Todorova
Ekaterina Krasimirova
Georgi Vasilev
Sevdalin Nachev
Dobroslav Kyurkchiev
author_sort Kalina Tumangelova-Yuzeir
collection DOAJ
description Mesenchymal stem cells (MSCs) possess immunosuppressive properties and have been described in the tumor microenvironment of glioblastoma multiforme (GBM). This manuscript has two major topics—first, to describe isolated and cultured MSCs derived from GBM (GB-MSCs) and second, to examine their in vitro immunosuppressive capacity. Our results display cells with morphology and phenotype, clonogenic ability, and osteogenic potential, typical for MSCs. Furthermore, the cultured cells show intracellular expression of the neural markers Nestin and GFAP. They express PD-L1 and secrete TGFβ, CCL-2, PGE2, IL-6, and sVEGF. Coculturing of GB-MSCs with PBMCs isolated from healthy donors results in a decreased percentage of Th17 lymphocytes and an increased percentage of Tregs. Regarding the impact of GB-MSCs on monocytes, we establish an augmented expression of CD14 and CD86 along with diminished expression of HLA-DR and CD80, which is associated with tolerogenic phenotype monocyte-derived cells. In conclusion, our results describe in detail GBM-derived and cultured cells that meet the criteria for MSCs but at the same time express Nestin and GFAP. GB-MSCs express and secrete suppressive molecules, influencing in vitro T cells and monocytes, and are probably another factor involved in the immune suppression exerted by GBM.
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spelling doaj-art-abc8fb4e754342fa93bffb23339693142025-08-20T03:39:14ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/69046386904638Mesenchymal Stem Cells Derived and Cultured from Glioblastoma Multiforme Increase Tregs, Downregulate Th17, and Induce the Tolerogenic Phenotype of Monocyte-Derived CellsKalina Tumangelova-Yuzeir0Emanuil Naydenov1Ekaterina Ivanova-Todorova2Ekaterina Krasimirova3Georgi Vasilev4Sevdalin Nachev5Dobroslav Kyurkchiev6Laboratory of Clinical Immunology, University Hospital “St. Ivan Rilski,” Department of Clinical Laboratory and Clinical Immunology, Medical University of Sofia, Sofia 1431, BulgariaClinic of Neurosurgery, University Hospital “St. Ivan Rilski,” Medical University Sofia, 15 “Acad. Ivan Geshov” Str., 1431 Sofia, BulgariaLaboratory of Clinical Immunology, University Hospital “St. Ivan Rilski,” Department of Clinical Laboratory and Clinical Immunology, Medical University of Sofia, Sofia 1431, BulgariaLaboratory of Clinical Immunology, University Hospital “St. Ivan Rilski,” Department of Clinical Laboratory and Clinical Immunology, Medical University of Sofia, Sofia 1431, BulgariaLaboratory of Clinical Immunology, University Hospital “St. Ivan Rilski,” Department of Clinical Laboratory and Clinical Immunology, Medical University of Sofia, Sofia 1431, BulgariaLaboratory of Clinical Pathology, University Hospital “St. Ivan Rilski,” Medical University Sofia, 15 “Acad. Ivan Geshov” Str., 1431 Sofia, BulgariaLaboratory of Clinical Immunology, University Hospital “St. Ivan Rilski,” Department of Clinical Laboratory and Clinical Immunology, Medical University of Sofia, Sofia 1431, BulgariaMesenchymal stem cells (MSCs) possess immunosuppressive properties and have been described in the tumor microenvironment of glioblastoma multiforme (GBM). This manuscript has two major topics—first, to describe isolated and cultured MSCs derived from GBM (GB-MSCs) and second, to examine their in vitro immunosuppressive capacity. Our results display cells with morphology and phenotype, clonogenic ability, and osteogenic potential, typical for MSCs. Furthermore, the cultured cells show intracellular expression of the neural markers Nestin and GFAP. They express PD-L1 and secrete TGFβ, CCL-2, PGE2, IL-6, and sVEGF. Coculturing of GB-MSCs with PBMCs isolated from healthy donors results in a decreased percentage of Th17 lymphocytes and an increased percentage of Tregs. Regarding the impact of GB-MSCs on monocytes, we establish an augmented expression of CD14 and CD86 along with diminished expression of HLA-DR and CD80, which is associated with tolerogenic phenotype monocyte-derived cells. In conclusion, our results describe in detail GBM-derived and cultured cells that meet the criteria for MSCs but at the same time express Nestin and GFAP. GB-MSCs express and secrete suppressive molecules, influencing in vitro T cells and monocytes, and are probably another factor involved in the immune suppression exerted by GBM.http://dx.doi.org/10.1155/2019/6904638
spellingShingle Kalina Tumangelova-Yuzeir
Emanuil Naydenov
Ekaterina Ivanova-Todorova
Ekaterina Krasimirova
Georgi Vasilev
Sevdalin Nachev
Dobroslav Kyurkchiev
Mesenchymal Stem Cells Derived and Cultured from Glioblastoma Multiforme Increase Tregs, Downregulate Th17, and Induce the Tolerogenic Phenotype of Monocyte-Derived Cells
Stem Cells International
title Mesenchymal Stem Cells Derived and Cultured from Glioblastoma Multiforme Increase Tregs, Downregulate Th17, and Induce the Tolerogenic Phenotype of Monocyte-Derived Cells
title_full Mesenchymal Stem Cells Derived and Cultured from Glioblastoma Multiforme Increase Tregs, Downregulate Th17, and Induce the Tolerogenic Phenotype of Monocyte-Derived Cells
title_fullStr Mesenchymal Stem Cells Derived and Cultured from Glioblastoma Multiforme Increase Tregs, Downregulate Th17, and Induce the Tolerogenic Phenotype of Monocyte-Derived Cells
title_full_unstemmed Mesenchymal Stem Cells Derived and Cultured from Glioblastoma Multiforme Increase Tregs, Downregulate Th17, and Induce the Tolerogenic Phenotype of Monocyte-Derived Cells
title_short Mesenchymal Stem Cells Derived and Cultured from Glioblastoma Multiforme Increase Tregs, Downregulate Th17, and Induce the Tolerogenic Phenotype of Monocyte-Derived Cells
title_sort mesenchymal stem cells derived and cultured from glioblastoma multiforme increase tregs downregulate th17 and induce the tolerogenic phenotype of monocyte derived cells
url http://dx.doi.org/10.1155/2019/6904638
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