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Cytotherapy. 2017 Oct;19(10):1176-1188. doi: 10.1016/j.jcyt.2017.07.002. Epub 2017 Aug 8.

Therapy with mesenchymal stromal cells or conditioned medium reverse cardiac alterations in a high-fat diet-induced obesity model.

Author information

1
Center for Biotechnology and Cell Therapy, Salvador, BA, Brazil; Multicentric Program in Biochemistry and Molecular Biology, Federal University of Bahia, Salvador, BA, Brazil.
2
Center for Biotechnology and Cell Therapy, Salvador, BA, Brazil; Faculty of Biology, Federal University of Bahia, Salvador, BA, Brazil.
3
Faculty of Medicine, Federal University of Bahia, Salvador, BA, Brazil.
4
Center for Biotechnology and Cell Therapy, Salvador, BA, Brazil.
5
Faculty of Medicine, Federal University of Bahia, Salvador, BA, Brazil; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, BA, Brazil.
6
Faculty of Pharmacy, Federal University of Bahia, Salvador, BA, Brazil.
7
Center for Biotechnology and Cell Therapy, Salvador, BA, Brazil; National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, RJ, Brazil.
8
Center for Biotechnology and Cell Therapy, Salvador, BA, Brazil; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, BA, Brazil; National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, RJ, Brazil.
9
Center for Biotechnology and Cell Therapy, Salvador, BA, Brazil; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, BA, Brazil; National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, RJ, Brazil; Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, BA, Brazil. Electronic address: simonegm@ufba.br.

Abstract

BACKGROUND:

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:

cardiac dysfunction; cell therapy; mesenchymal stromal cells; obesity

PMID:
28801055
DOI:
10.1016/j.jcyt.2017.07.002
[Indexed for MEDLINE]

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