Combined therapy with adipose tissue-derived mesenchymal stromal cells and meglumine antimoniate controls lesion develop

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(2020) 11:374

RESEARCH

Open Access

Combined therapy with adipose tissuederived mesenchymal stromal cells and meglumine antimoniate controls lesion development and parasite load in murine cutaneous leishmaniasis caused by Leishmania amazonensis Tadeu Diniz Ramos1,2, Johnatas Dutra Silva3, Alessandra Marcia da Fonseca-Martins1, Juliana Elena da Silveira Pratti1, Luan Firmino-Cruz1, Diogo Maciel-Oliveira1, Julio Souza Dos-Santos1, João Ivo Nunes Tenorio4, Almair Ferreira de Araujo4, Célio Geraldo Freire-de-Lima2, Bruno Lourenço Diaz4, Fernanda Ferreira Cruz3, Patricia Rieken Macedo Rocco3,5*† and Herbert Leonel de Matos Guedes1,6,7*†

Abstract Background: Leishmaniasis is a neglected disease caused by Leishmania spp. One of its characteristics is an imbalance of host immune responses to foster parasite survival. In this setting, mesenchymal stromal cells (MSCs) may be a viable therapeutic alternative, given their well-established immunomodulatory potential. In this study, we compared the effects of therapy with bone marrow (BM)- and adipose tissue (AD)-derived MSCs in leishmaniasis caused by Leishmania amazonensis in C57BL/6 mice. After determining the most effective MSC source, we then combined these cells with meglumine antimoniate (a pentavalent antimonial commonly used for the treatment of leishmaniasis) to treat the infected mice. Methods: In vitro, co-culture of AD-MSCs and BM-MSCs with Leishmania amazonensis-infected macrophages was performed to understand the influence of both MSC sources in infected cells. In vivo, infected C57BL/6 mice were treated with phosphate-buffered saline (PBS), AD-MSCs and BM-MSCs, and then meglumine antimoniate was combined with MSCs from the most effective source. (Continued on next page)

* Correspondence: [email protected]; [email protected]; [email protected] † Patricia Rieken Macedo Rocco and Herbert Leonel de Matos Guedes share senior authorships. 3 Laboratório de Investigação Pulmonar, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil 1 Grupo de Imunologia e Vacinologia, Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you wil