Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy

Frontiers in Immunology
Daniela N SilvaMilena B P Soares

Abstract

Genetic modification of mesenchymal stem cells (MSCs) is a promising strategy to improve their therapeutic effects. Granulocyte-colony stimulating factor (G-CSF) is a growth factor widely used in the clinical practice with known regenerative and immunomodulatory actions, including the mobilization of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Here we evaluated the therapeutic potential of MSCs overexpressing G-CSF (MSC_G-CSF) in a model of inflammatory cardiomyopathy due to chronic Chagas disease. C57BL/6 mice were treated with wild-type MSCs, MSC_G-CSF, or vehicle (saline) 6 months after infection with Trypanosoma cruzi. Transplantation of MSC_G-CSF caused an increase in the number of circulating leukocytes compared to wild-type MSCs. Moreover, G-CSF overexpression caused an increase in migration capacity of MSCs to the hearts of infected mice. Transplantation of either MSCs or MSC_G-CSF improved exercise capacity, when compared to saline-treated chagasic mice. MSC_G-CSF mice, however, were more potent than MSCs in reducing the number of infiltrating leukocytes and fibrosis in the heart. Similarly, MSC_G-CSF-treated mice presented significantly lower levels of inflammatory mediators, such as IFNγ,...Continue Reading

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Citations

Sep 26, 2020·Frontiers in Cell and Developmental Biology·Patricia Kauanna Fonseca DamascenoMilena Botelho Pereira Soares
Apr 23, 2020·Frontiers in Immunology·Emanuelle de Souza SantosMilena Botelho Pereira Soares
Nov 24, 2019·Seminars in Cell & Developmental Biology·Jason S RockelSowmya Viswanathan
Apr 4, 2021·International Journal of Molecular Sciences·Yoojin SeoHyung-Sik Kim
Jul 11, 2021·Cell Biology International·Vijayendran GovindasamySoon-Keng Cheong
Jul 25, 2021·International Journal of Molecular Sciences·Fernanda GubertGisele Zapata-Sudo

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Methods Mentioned

BETA
transgenic
FACS
light microscopy
PCR
flow cytometry

Software Mentioned

BD
GraphPad Prism
Harmony
Operetta
Chart
FlowJo
FacsDiva
Image Pro Plus

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