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

Author(s):Show less -

de Freitas, Carla Longo ^{[1, 2]} ; Polonio, Carolina Manganeli ^{[1, 2]} ; Brandao, Wesley Nogueira ^{[1, 2]} ; Rossato, Cristiano ^{[1, 2]} ; Zanluqui, Nagela Ghabdan ^{[3, 1, 2]} ; de Oliveira, Lilian Gomes ^{[1, 2]} ; de Oliveira, Marilia Garcia ^{[1, 2]} ; Evangelista, Lucila Pires ^{[2, 4]} ; Halpern, Silvio ^{[2, 5]} ; Maluf, Mariangela ^{[2, 6]} ; Czresnia, Carlos Eduardo ^{[2, 4]} ; Perin, Paulo ^{[2, 6]} ; de Almeida, Danilo Candido ^{[2, 7]} ; Schatzmman Peron, Jean Pierre ^{[3, 1, 2]}

Affiliation

^[1] Univ Sao Paulo, Neuroimmune Interact Lab, Dept Immunol, Av Prof Lineu Prestes, 1730 Lab 232, Cidade Univ, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Sci Platform Pasteur USP, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Immunopathol & Allergy Post Grad Program, Sao Paulo - Brazil

^[4] Celula Mater Clin, Reprod Med Div, Sao Paulo - Brazil

^[5] Halpern Clin, Reprod Med Div, Sao Paulo - Brazil

^[6] CEERH Clin, Reprod Med Div, Sao Paulo - Brazil

^[7] Fed Univ Sao Paulo UNIFESP, Nephrol Div, Sao Paulo - Brazil

• Document type: Journal article
• Source: STEM CELL REVIEWS AND REPORTS; AUG 2021.
• Web of Science Citations: 0

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-gamma 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. (AU)

• FAPESP's process: 20/06145-4 - Immunopathogenesis of COVID-19 in experimental models and nasal vaccine anti-SARS-CoV-2
• Grantee: Jean Pierre Schatzmann Peron
• Support type: Regular Research Grants
• FAPESP's process: 16/07371-2 - Characterization of the role of T CD8+ lymphocytes in Zika virus infection
• Grantee: Nagela Ghabdan Zanluqui
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/10242-5 - The role of ionotropic glutamate receptor NMDA in innate and adaptive immune cells from intestinal mucosa in murine experimental model
• Grantee: Marília Garcia de Oliveira
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/11828-0 - Evaluation of the microRNAs role in the immunopathogenesis of microcephaly caused by Zika virus in experimental models
• Grantee: Carolina Manganeli Polonio
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/22504-1 - TAM receptors and their ligands Gas6 and Pros1 on the ZIKV Congenital Syndrome in Experimental Models
• Grantee: Jean Pierre Schatzmann Peron
• Support type: Regular Research Grants
• FAPESP's process: 17/26170-0 - Neuroimmunology in experimental models of Autoimmune Encephalomyelitis and Congenital Zika Syndrome: physiopathogenesis, susceptibility, cellular therapy, vaccination
• Grantee: Jean Pierre Schatzmann Peron
• Support type: Research Projects - Thematic Grants