{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:23:41Z","timestamp":1782865421138,"version":"3.54.5"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>New therapeutic options are necessary for patients with chronic Chagas disease, a leading cause of heart failure in Latin American countries. Stem cell therapy focused on improving cardiac function is a promising approach for treating heart disease. Here, we evaluated the therapeutic effects of cardiac mesenchymal stem cells (CMSCs) in a mouse model of chronic Chagas disease.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>CMSCs were isolated from green fluorescent protein (GFP) transgenic C57BL\/6 mouse hearts and tested for adipogenic, osteogenic, chondrogenic, endothelial, and cardiogenic differentiation potentials evaluated by histochemical and immunofluorescence techniques. A lymphoproliferation assay was performed to evaluate the immunomodulatory activity of CMSCs. To investigate the therapeutic potential of CMSCs, C57BL\/6 mice chronically infected with <jats:italic>Trypanosoma cruzi<\/jats:italic> were treated with 10<jats:sup>6<\/jats:sup> CMSCs or saline (control) by echocardiography-guided injection into the left ventricle wall. All animals were submitted to cardiac histopathological and immunofluorescence analysis in heart sections from chagasic mice. Analysis by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was performed in the heart to evaluate the expression of cytokines involved in the inflammatory response.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>CMSCs demonstrated adipogenic, osteogenic, and chondrogenic differentiation potentials. Moreover, these cells expressed endothelial cell and cardiomyocyte features upon defined stimulation culture conditions and displayed immunosuppressive activity <jats:italic>in vitro<\/jats:italic>. After intramyocardial injection, GFP<jats:sup>+<\/jats:sup> CMSCs were observed in heart sections of chagasic mice one week later; however, no observed GFP<jats:sup>+<\/jats:sup> cells co-expressed troponin T or connexin-43. Histopathological analysis revealed that CMSC-treated mice had a significantly decreased number of inflammatory cells, but no reduction in fibrotic area, two months after treatment. Analysis by qRT-PCR demonstrated that cell therapy significantly decreased tumor necrosis factor-alpha expression and increased transforming growth factor-beta in heart samples.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>We conclude that the CMSCs exert a protective effect in chronic chagasic cardiomyopathy primarily through immunomodulation.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/scrt470","type":"journal-article","created":{"date-parts":[[2014,7,2]],"date-time":"2014-07-02T08:08:45Z","timestamp":1404288525000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Intramyocardial transplantation of cardiac mesenchymal stem cells reduces myocarditis in a model of chronic Chagas disease cardiomyopathy"],"prefix":"10.1186","volume":"5","author":[{"given":"Daniela Nascimento","family":"Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Solano","family":"de Freitas Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine Machado","family":"Azevedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Fraga","family":"Vasconcelos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rejane Hughes","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena Botelho Pereira","family":"Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Ribeiro","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,7,1]]},"reference":[{"key":"379_CR1","doi-asserted-by":"publisher","first-page":"2454","DOI":"10.1161\/CIRCULATIONAHA.111.067785","volume":"125","author":"R Ribeiro Dos Santos","year":"2012","unstructured":"Ribeiro Dos Santos R, Rassi S, Feitosa G, Grecco OT, Rassi A, da Cunha AB, de Carvalho VB, Guarita-Souza LC, de Oliveira W, Tura BR, Soares MB, de Carvalho AC C, Chagas Arm of the MiHeart Study Investigators: Cell therapy in Chagas cardiomyopathy (Chagas arm of the multicenter randomized trial of cell therapy in cardiopathies study): a multicenter randomized trial. 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