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https://www.arca.fiocruz.br/handle/icict/25070
THERAPY WITH MESENCHYMAL STROMAL CELLS OR CONDITIONED MEDIUM REVERSE CARDIAC ALTERATIONS IN A HIGH-FAT DIET-INDUCED OBESITY MODEL
Terapia celular
Células estomatais mesenquimatosas
Obesidade
Author
Daltro, Pamela Santana
Barreto, Breno Cardim
Silva, P G
Chenaud Neto, Paulo
Sousa Filho, P H F
Santana Neta, D
Carvalho, Gisele Batista
Silva, D N
Paredes, Bruno Diaz
Alcantara, Adriano Costa de
Freitas, Luiz Antonio Rodrigues de
Couto, Ricardo David
Santos, Ricardo Ribeiro dos
Souza, Bruno Solano de Freitas
Soares, Milena Botelho Pereira
Macambira, Simone Garcia
Barreto, Breno Cardim
Silva, P G
Chenaud Neto, Paulo
Sousa Filho, P H F
Santana Neta, D
Carvalho, Gisele Batista
Silva, D N
Paredes, Bruno Diaz
Alcantara, Adriano Costa de
Freitas, Luiz Antonio Rodrigues de
Couto, Ricardo David
Santos, Ricardo Ribeiro dos
Souza, Bruno Solano de Freitas
Soares, Milena Botelho Pereira
Macambira, Simone Garcia
Affilliation
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Federal University of Bahia. Multicentric Program in Biochemistry and Molecular Biology. Salvador, BA, Brazil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Federal University of Bahia. Faculty of Biology. Salvador, BA, Brazil
Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil
Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil
Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil
Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Federal University of Bahia. Faculty of Pharmacy. Salvador, BA, Brazil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / National Institute of Science andTechnology for Regenerative Medicine. Rio de Janeiro, RJ, Brazil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science andTechnology for Regenerative Medicine. Rio de Janeiro, RJ, Brazil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science andTechnology for Regenerative Medicine. Rio de Janeiro, RJ, Brazil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science andTechnology for Regenerative Medicine. Rio de Janeiro, RJ, Brazil / Federal University of Bahia. Institute of Health Sciences. Department of Biochemistry and Biophysics. Salvador, BA, Brazil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Federal University of Bahia. Faculty of Biology. Salvador, BA, Brazil
Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil
Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil
Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil
Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Federal University of Bahia. Faculty of Pharmacy. Salvador, BA, Brazil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / National Institute of Science andTechnology for Regenerative Medicine. Rio de Janeiro, RJ, Brazil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science andTechnology for Regenerative Medicine. Rio de Janeiro, RJ, Brazil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science andTechnology for Regenerative Medicine. Rio de Janeiro, RJ, Brazil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science andTechnology for Regenerative Medicine. Rio de Janeiro, RJ, Brazil / Federal University of Bahia. Institute of Health Sciences. Department of Biochemistry and Biophysics. Salvador, BA, Brazil
Abstract
Obesity is associated with numerous cardiac complications, including arrhythmias, cardiac fibrosis, remodeling and heart failure. Here we evaluated the therapeutic potential of mesenchymal stromal cells (MSCs) and their conditioned medium (CM) to treat cardiac complications in a mouse model of high-fat diet (HFD)-induced obesity.Methods. After
obesity induction and HFD withdrawal, obese mice were treated with MSCs, CM or vehicle. Cardiac function was assessed
using electrocardiography, echocardiography and treadmill test. Body weight and biochemical parameters were evaluated.
Cardiac tissue was used for real time (RT)-polymerase chain reaction (PCR) and histopathologic analysis. Results/
Discussion. Characterization of CM by protein array showed the presence of different cytokines and growth factors, including
chemokines, osteopontin, cystatin C, Serpin E1 and Gas 6. HFD-fed mice presented cardiac arrhythmias, altered cardiac
gene expression and fibrosis reflected in physical exercise incapacity associated with obesity and diabetes. Administration
of MSCs or CM improved arrhythmias and exercise capacity. This functional improvement correlated with normalization
of GATA4 gene expression in the hearts of MSC- or CM-treated mice. The gene expression of connexin 43, troponin I,
adiponectin, transforming growth factor (TGF) β, peroxisome proliferator activated receptor gamma (PPARγ), insulin-like
growth factor 1 (IGF-1), matrix metalloproteinase-9 (MMP9) and tissue inhibitor of metalloproteinases 1 (TIMP1) were
significantly reduced in MSCs, but not in CM-treated mice. Moreover, MSC or CM administration reduced the intensity
of cardiac fibrosis. Conclusion. Our results suggest that MSCs and CM have a recovery effect on cardiac disturbances due
to obesity and corroborate to the paracrine action of MSCs in heart disease models.
Keywords in Portuguese
Disfunção cardíacaTerapia celular
Células estomatais mesenquimatosas
Obesidade
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