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. 2022 Feb;18(2):609-625.
doi: 10.1007/s12015-021-10226-7. Epub 2021 Aug 28.

Human Fallopian Tube - Derived Mesenchymal Stem Cells Inhibit Experimental Autoimmune Encephalomyelitis by Suppressing Th1/Th17 Activation and Migration to Central Nervous System

Carla Longo de Freitas  1   2 , Carolina Manganeli Polonio  1   2 , Wesley Nogueira Brandão  1   2 , Cristiano Rossato  1   2 , Nágela Ghabdan Zanluqui  1   3   2 , Lilian Gomes de Oliveira  1   2 , Marília Garcia de Oliveira  1   2 , Lucila Pires Evangelista  4   2 , Silvio Halpern  5   2 , Mariangela Maluf  6   2 , Carlos Eduardo Czresnia  4   2 , Paulo Perin  6   2 , Danilo Candido de Almeida  7   2 , Jean Pierre Schatzmman Peron  8   9   10
Affiliations

Human Fallopian Tube - Derived Mesenchymal Stem Cells Inhibit Experimental Autoimmune Encephalomyelitis by Suppressing Th1/Th17 Activation and Migration to Central Nervous System

Carla Longo de Freitas et al. Stem Cell Rev Rep. 2022 Feb.

Abstract

Mesenchymal stem cells comprise a natural reservoir of undifferentiated cells within adult tissues. Given their self-renewal, multipotency, regenerative potential and immunomodulatory properties, MSCs have been reported as a promising cell therapy for the treatment of different diseases, including neurodegenerative and autoimmune diseases. In this study, we investigated the immunomodulatory properties of human tubal mesenchymal stem cells (htMSCs) using the EAE model. htMSCs were able to suppress dendritic cells activation downregulating antigen presentation-related molecules, such as MHCII, CD80 and CD86, while impairing IFN-γ and IL-17 and increasing IL-10 and IL-4 secretion. It further correlated with milder disease scores when compared to the control group due to fewer leukocytes infiltrating the CNS, specially Th1 and Th17 lymphocytes, associated with increased IL-10 secreting Tr1 cells. Conversely, microglia were less activated and infiltrating mononuclear cells secreted higher levels of IL-4 and IL-10 and expressed reduced chemokine receptors as CCR4, CCR6 and CCR8. qPCR of the spinal cords revealed upregulation of indoleamine-2,3-dioxygenase (IDO) and brain derived neurotrophic factor (BDNF). Taken together, here evidenced the potential of htMSCs as an alternative for the treatment of inflammatory, autoimmune or neurodegenerative diseases.

Keywords: Dendritic cells; EAE; Immunomodulation; Lymphocytes; Mesenchymal stem cell.

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