Galectin-3 Knockdown Impairs Survival, Migration, and Immunomodulatory Actions of Mesenchymal Stromal Cells in a Mouse Model of Chagas Disease Cardiomyopathy.
Bruno Solano de Freitas SouzaKátia Nunes da SilvaDaniela Nascimento SilvaVinícius Pinto Costa RochaBruno Diaz ParedesCarine Machado AzevedoCarolina Kymie NonakaGisele Batista CarvalhoJuliana Fraga VasconcelosRicardo Ribeiro Dos SantosMilena Botelho Pereira SoaresPublished in: Stem cells international (2017)
Therapies based on transplantation of mesenchymal stromal cells (MSC) hold promise for the management of inflammatory disorders. In chronic Chagas disease cardiomyopathy (CCC), caused by chronic infection with Trypanosoma cruzi, the exacerbated immune response plays a critical pathophysiological role and can be modulated by MSC. Here, we investigated the role of galectin-3 (Gal-3), a beta-galactoside-binding lectin with several actions on immune responses and repair process, on the immunomodulatory potential of MSC. Gal-3 knockdown in MSC did not affect the immunophenotype or differentiation potential. However, Gal-3 knockdown MSC showed decreased proliferation, survival, and migration. Additionally, when injected intraperitoneally into mice with CCC, Gal-3 knockdown MSC showed impaired migration in vivo. Transplantation of control MSC into mice with CCC caused a suppression of cardiac inflammation and fibrosis, reducing expression levels of CD45, TNFα, IL-1β, IL-6, IFNγ, and type I collagen. In contrast, Gal-3 knockdown MSC were unable to suppress the immune response or collagen synthesis in the hearts of mice with CCC. Finally, infection with T. cruzi demonstrated parasite survival in wild-type but not in Gal-3 knockdown MSC. These findings demonstrate that Gal-3 plays a critical role in MSC survival, proliferation, migration, and therapeutic potential in CCC.
Keyphrases
- big data
- immune response
- artificial intelligence
- machine learning
- wild type
- heart failure
- mouse model
- oxidative stress
- dendritic cells
- bone marrow
- trypanosoma cruzi
- poor prognosis
- signaling pathway
- high fat diet induced
- mass spectrometry
- deep learning
- computed tomography
- cell therapy
- high resolution
- mesenchymal stem cells
- inflammatory response
- binding protein
- long non coding rna
- low density lipoprotein