Dexamethasone priming enhances stemness and immunomodulatory property of tissue-specific human mesenchymal stem cells

Abstract Background Human Mesenchymal Stem Cells (hMSCs) represent a promising cell source for cell-based therapy in autoimmune diseases and other degenerative disorders due to their immunosuppressive, anti-inflammatory and regenerative potentials. Belonging to a glucocorticoid family, Dexamethasone...

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Autores principales:	Sonali Rawat, Vatsla Dadhwal, Sujata Mohanty
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Mesenchymal stem cell Immunomodulatory Glucocorticoids Dexamethasone Autoimmune diseases Anti-inflammatory Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3d11b4baf97b48fb9837530850f49556
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spelling	oai:doaj.org-article:3d11b4baf97b48fb9837530850f495562021-11-07T12:03:31ZDexamethasone priming enhances stemness and immunomodulatory property of tissue-specific human mesenchymal stem cells10.1186/s12861-021-00246-41471-213Xhttps://doaj.org/article/3d11b4baf97b48fb9837530850f495562021-11-01T00:00:00Zhttps://doi.org/10.1186/s12861-021-00246-4https://doaj.org/toc/1471-213XAbstract Background Human Mesenchymal Stem Cells (hMSCs) represent a promising cell source for cell-based therapy in autoimmune diseases and other degenerative disorders due to their immunosuppressive, anti-inflammatory and regenerative potentials. Belonging to a glucocorticoid family, Dexamethasone (Dex) is a powerful anti-inflammatory compound that is widely used as therapy in autoimmune disease conditions or allogeneic transplantation. However, minimal immunomodulatory effect of hMSCs may limit their therapeutic uses. Moreover, the effect of glucocorticoids on the immunomodulatory molecules or other regenerative properties of tissue-specific hMSCs remains unknown. Method Herein, we evaluated the in vitro effect of Dex at various dose concentrations and time intervals, 1000 ng/ml, 2000 ng/ml, 3000 ng/ml and 24 h, 48 h respectively, on the basic characteristics and immunomodulatory properties of Bone marrow derived MSC (BM-MSCs), Adipose tissue derived MSCs (AD-MSCs), Dental Pulp derived MSC (DP-MSCs) and Umbilical cord derived MSCs (UC-MSCs). Results The present study indicated that the concentration of Dex did not ramify the cellular morphology nor showed cytotoxicity as well as conserved the basic characteristics of tissue specific hMSCs including cell proliferation and surface marker profiling. However, quite interestingly it was observed that the stemness markers (Oct-4, Sox-2, Nanog and Klf-4) showed a significant upregulation in DP-MSCs and AD-MSCs followed by UC-MSCs and BM-MSCs. Additionally, immunomodulatory molecules, Prostaglandin E-2 (PGE-2), Indoleamine- 2,3-dioxygenase (IDO) and Human Leukocyte Antigen-G (HLA-G) were seen to be upregulated in a dose-dependent manner. Moreover, there was a differential response of tissue specific hMSCs after pre-conditioning with Dex during mixed lymphocyte reaction, wherein UC-MSCs and DP-MSCs showed enhanced immunosuppression as compared to AD-MSCs and BM-MSCs, thereby proving to be a better candidate for therapeutic applications in immune-related diseases. Conclusion Dex preconditioning improved the hMSCs immunomodulatory property and may have reduced the challenge associated with minimal potency and strengthen their therapeutic efficacy. Graphical Abstract Preconditioning of tissue specific hMSCs with dexamethasone biomanufacturers the enhanced potential hMSCs with better stemness and immunomodulatory properties for future therapeutics.Sonali RawatVatsla DadhwalSujata MohantyBMCarticleMesenchymal stem cellImmunomodulatoryGlucocorticoidsDexamethasoneAutoimmune diseasesAnti-inflammatoryBiology (General)QH301-705.5ENBMC Developmental Biology, Vol 21, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mesenchymal stem cell Immunomodulatory Glucocorticoids Dexamethasone Autoimmune diseases Anti-inflammatory Biology (General) QH301-705.5
spellingShingle	Mesenchymal stem cell Immunomodulatory Glucocorticoids Dexamethasone Autoimmune diseases Anti-inflammatory Biology (General) QH301-705.5 Sonali Rawat Vatsla Dadhwal Sujata Mohanty Dexamethasone priming enhances stemness and immunomodulatory property of tissue-specific human mesenchymal stem cells
description	Abstract Background Human Mesenchymal Stem Cells (hMSCs) represent a promising cell source for cell-based therapy in autoimmune diseases and other degenerative disorders due to their immunosuppressive, anti-inflammatory and regenerative potentials. Belonging to a glucocorticoid family, Dexamethasone (Dex) is a powerful anti-inflammatory compound that is widely used as therapy in autoimmune disease conditions or allogeneic transplantation. However, minimal immunomodulatory effect of hMSCs may limit their therapeutic uses. Moreover, the effect of glucocorticoids on the immunomodulatory molecules or other regenerative properties of tissue-specific hMSCs remains unknown. Method Herein, we evaluated the in vitro effect of Dex at various dose concentrations and time intervals, 1000 ng/ml, 2000 ng/ml, 3000 ng/ml and 24 h, 48 h respectively, on the basic characteristics and immunomodulatory properties of Bone marrow derived MSC (BM-MSCs), Adipose tissue derived MSCs (AD-MSCs), Dental Pulp derived MSC (DP-MSCs) and Umbilical cord derived MSCs (UC-MSCs). Results The present study indicated that the concentration of Dex did not ramify the cellular morphology nor showed cytotoxicity as well as conserved the basic characteristics of tissue specific hMSCs including cell proliferation and surface marker profiling. However, quite interestingly it was observed that the stemness markers (Oct-4, Sox-2, Nanog and Klf-4) showed a significant upregulation in DP-MSCs and AD-MSCs followed by UC-MSCs and BM-MSCs. Additionally, immunomodulatory molecules, Prostaglandin E-2 (PGE-2), Indoleamine- 2,3-dioxygenase (IDO) and Human Leukocyte Antigen-G (HLA-G) were seen to be upregulated in a dose-dependent manner. Moreover, there was a differential response of tissue specific hMSCs after pre-conditioning with Dex during mixed lymphocyte reaction, wherein UC-MSCs and DP-MSCs showed enhanced immunosuppression as compared to AD-MSCs and BM-MSCs, thereby proving to be a better candidate for therapeutic applications in immune-related diseases. Conclusion Dex preconditioning improved the hMSCs immunomodulatory property and may have reduced the challenge associated with minimal potency and strengthen their therapeutic efficacy. Graphical Abstract Preconditioning of tissue specific hMSCs with dexamethasone biomanufacturers the enhanced potential hMSCs with better stemness and immunomodulatory properties for future therapeutics.
format	article
author	Sonali Rawat Vatsla Dadhwal Sujata Mohanty
author_facet	Sonali Rawat Vatsla Dadhwal Sujata Mohanty
author_sort	Sonali Rawat
title	Dexamethasone priming enhances stemness and immunomodulatory property of tissue-specific human mesenchymal stem cells
title_short	Dexamethasone priming enhances stemness and immunomodulatory property of tissue-specific human mesenchymal stem cells
title_full	Dexamethasone priming enhances stemness and immunomodulatory property of tissue-specific human mesenchymal stem cells
title_fullStr	Dexamethasone priming enhances stemness and immunomodulatory property of tissue-specific human mesenchymal stem cells
title_full_unstemmed	Dexamethasone priming enhances stemness and immunomodulatory property of tissue-specific human mesenchymal stem cells
title_sort	dexamethasone priming enhances stemness and immunomodulatory property of tissue-specific human mesenchymal stem cells
publisher	BMC
publishDate	2021
url	https://doaj.org/article/3d11b4baf97b48fb9837530850f49556
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Dexamethasone priming enhances stemness and immunomodulatory property of tissue-specific human mesenchymal stem cells

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