Título:	Regulatory T-Cell enhancement, expression of adhesion molecules, and production of anti-inflammatory factors are differentially modulated by spheroid-cultured mesenchymal stem cells
Autor(es):	Carvalho, Amandda Évelin Silva de Silva, Ingrid Gracielle Martins da Corrêa, José Raimundo Araujo, Felipe Saldanha de
ORCID:	https://orcid.org/0000-0001-7654-044X
Afiliação do autor:	University of Brasília, Hematology and Stem Cells Laboratory University of Brasília, Molecular Pharmacology Laboratory University of Brasília, Microscopy and Microanalysis Laboratory University of Brasília, Microscopy and Microanalysis Laboratory University of Brasília, Hematology and Stem Cells Laboratory
Assunto:	Células-tronco mesenquimais Células T Moléculas de adesão celular
Data de publicação:	18-Nov-2022
Editora:	MDPI
Referência:	CARVALHO, Amanda Évelin Silva de et. al. Regulatory T-Cell enhancement, expression of adhesion molecules, and production of anti-inflammatory factors are differentially modulated by spheroid-cultured mesenchymal stem cells. International Journal of Molecular Sciences, [s. l.], v. 23, 14349, 2022. DOI: https://doi.org/10.3390/ijms232214349. Disponível em: https://www.mdpi.com/1422-0067/23/22/14349. Acesso em: 25 set. 2023.
Abstract:	The culture of mesenchymal stem cells (MSCs) as spheroids promotes a more physiological cellular behavior, as it more accurately reflects the biological microenvironment. Nevertheless, mixed results have been found regarding the immunosuppressive properties of spheroid-cultured MSCs (3D-MSCs), the mechanisms of immunoregulation of 3D-MSCs being scarcely described at this point. In the present study, we constructed spheroids from MSCs and compared their immunosuppressive potential with that of MSCs cultured in monolayer (2D-MSCs). First, we evaluated the ability of 2D-MSCs and 3D-MSCs to control the activation and proliferation of T-cells. Next, we evaluated the percentage of regulatory T-cells (Tregs) after the co-culturing of peripheral blood mononuclear cells (PBMCs) with 2D-MSCs and 3D-MSCs. Finally, we investigated the expression of adhesion molecules, as well as the expressions of several anti-inflammatory transcripts in 2D-MSCs and 3DMSCs maintained in both inflammatory and non-inflammatory conditions. Interestingly, our data show that several anti-inflammatory genes are up-regulated in 3D-MSCs, and that these cells can control T-cell proliferation. Nevertheless, 2D-MSCs are more efficient in suppressing the immune cell proliferation. Importantly, contrary to what was observed in 3D-MSCs, the expressions of ICAM-1 and VCAM-1 are significantly upregulated in 2D-MSCs exposed to an inflammatory environment. Furthermore, only 2D-MSCs are able to promote the enhancement of Tregs. Taken together, our data clearly show that the immunosuppressive potential of MSCs is significantly impacted by their shape, and highlights the important role of cell–cell adhesion molecules for optimal MSC immunomodulatory function.
Unidade Acadêmica:	Instituto de Ciências Biológicas (IB) Faculdade de Ciências da Saúde (FS) Departamento de Farmácia (FS FAR)
Licença:	(CC-BY) Copyright: © 2022 by the authors. 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/).
DOI:	https://doi.org/10.3390/ijms232214349
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