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The Effects of Immunosuppressive Drugs on the Characteristics and Functional Properties of Bone Marrow-Derived Stem Cells Isolated from Patients with Diabetes Mellitus and Peripheral Arterial Disease

Background: Diabetic patients (DPs) with foot ulcers can receive autologous cell therapy (ACT) as a last therapeutic option. Even DPs who have undergone organ transplantation and are using immunosuppressive (IS) drugs can be treated by ACT. The aim of our study was to analyze the effects of IS drugs...

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Autores principales: Husakova, Jitka, Echalar, Barbora, Kossl, Jan, Palacka, Katerina, Fejfarova, Vladimira, Dubsky, Michal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377428/
https://www.ncbi.nlm.nih.gov/pubmed/37509511
http://dx.doi.org/10.3390/biomedicines11071872
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author Husakova, Jitka
Echalar, Barbora
Kossl, Jan
Palacka, Katerina
Fejfarova, Vladimira
Dubsky, Michal
author_facet Husakova, Jitka
Echalar, Barbora
Kossl, Jan
Palacka, Katerina
Fejfarova, Vladimira
Dubsky, Michal
author_sort Husakova, Jitka
collection PubMed
description Background: Diabetic patients (DPs) with foot ulcers can receive autologous cell therapy (ACT) as a last therapeutic option. Even DPs who have undergone organ transplantation and are using immunosuppressive (IS) drugs can be treated by ACT. The aim of our study was to analyze the effects of IS drugs on the characteristics of bone marrow-derived stem cells (BM-MSCs). Methods: The cells were isolated from the bone marrow of DPs, cultivated for 14–18 days, and phenotypically characterized using flow cytometry. These precursor cells were cultured in the presence of various IS drugs. The impact of IS drugs on metabolic activity was measured using a WST-1 assay, and the expression of genes for immunoregulatory molecules was detected through RT-PCR. Cell death was analyzed through the use of flow cytometry, and the production of cytokines was determined by ELISA. Results: The mononuclear fraction of cultured cells contained mesenchymal stem cells (CD45(−)CD73(+)CD90(+)CD105(+)), myeloid angiogenic cells (CD45(+)CD146(−)), and endothelial colony-forming cells (CD45(−)CD146(+)). IS drugs inhibited metabolic activity, the expression of genes for immunoregulatory molecules, the production of cytokines, and the viability of the cells. Conclusions: The results indicate that IS drugs in a dose-dependent manner had a negative impact on the properties of BM-MSCs used to treat ischemic diabetic foot ulcers, and that these drugs could affect the therapeutic potential of BM-MSCs.
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spelling pubmed-103774282023-07-29 The Effects of Immunosuppressive Drugs on the Characteristics and Functional Properties of Bone Marrow-Derived Stem Cells Isolated from Patients with Diabetes Mellitus and Peripheral Arterial Disease Husakova, Jitka Echalar, Barbora Kossl, Jan Palacka, Katerina Fejfarova, Vladimira Dubsky, Michal Biomedicines Article Background: Diabetic patients (DPs) with foot ulcers can receive autologous cell therapy (ACT) as a last therapeutic option. Even DPs who have undergone organ transplantation and are using immunosuppressive (IS) drugs can be treated by ACT. The aim of our study was to analyze the effects of IS drugs on the characteristics of bone marrow-derived stem cells (BM-MSCs). Methods: The cells were isolated from the bone marrow of DPs, cultivated for 14–18 days, and phenotypically characterized using flow cytometry. These precursor cells were cultured in the presence of various IS drugs. The impact of IS drugs on metabolic activity was measured using a WST-1 assay, and the expression of genes for immunoregulatory molecules was detected through RT-PCR. Cell death was analyzed through the use of flow cytometry, and the production of cytokines was determined by ELISA. Results: The mononuclear fraction of cultured cells contained mesenchymal stem cells (CD45(−)CD73(+)CD90(+)CD105(+)), myeloid angiogenic cells (CD45(+)CD146(−)), and endothelial colony-forming cells (CD45(−)CD146(+)). IS drugs inhibited metabolic activity, the expression of genes for immunoregulatory molecules, the production of cytokines, and the viability of the cells. Conclusions: The results indicate that IS drugs in a dose-dependent manner had a negative impact on the properties of BM-MSCs used to treat ischemic diabetic foot ulcers, and that these drugs could affect the therapeutic potential of BM-MSCs. MDPI 2023-06-30 /pmc/articles/PMC10377428/ /pubmed/37509511 http://dx.doi.org/10.3390/biomedicines11071872 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Husakova, Jitka
Echalar, Barbora
Kossl, Jan
Palacka, Katerina
Fejfarova, Vladimira
Dubsky, Michal
The Effects of Immunosuppressive Drugs on the Characteristics and Functional Properties of Bone Marrow-Derived Stem Cells Isolated from Patients with Diabetes Mellitus and Peripheral Arterial Disease
title The Effects of Immunosuppressive Drugs on the Characteristics and Functional Properties of Bone Marrow-Derived Stem Cells Isolated from Patients with Diabetes Mellitus and Peripheral Arterial Disease
title_full The Effects of Immunosuppressive Drugs on the Characteristics and Functional Properties of Bone Marrow-Derived Stem Cells Isolated from Patients with Diabetes Mellitus and Peripheral Arterial Disease
title_fullStr The Effects of Immunosuppressive Drugs on the Characteristics and Functional Properties of Bone Marrow-Derived Stem Cells Isolated from Patients with Diabetes Mellitus and Peripheral Arterial Disease
title_full_unstemmed The Effects of Immunosuppressive Drugs on the Characteristics and Functional Properties of Bone Marrow-Derived Stem Cells Isolated from Patients with Diabetes Mellitus and Peripheral Arterial Disease
title_short The Effects of Immunosuppressive Drugs on the Characteristics and Functional Properties of Bone Marrow-Derived Stem Cells Isolated from Patients with Diabetes Mellitus and Peripheral Arterial Disease
title_sort effects of immunosuppressive drugs on the characteristics and functional properties of bone marrow-derived stem cells isolated from patients with diabetes mellitus and peripheral arterial disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377428/
https://www.ncbi.nlm.nih.gov/pubmed/37509511
http://dx.doi.org/10.3390/biomedicines11071872
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