Biological properties of cardiac mesenchymal stem cells in rats with diabetic cardiomyopathy

Diógenes Rodrigo Maronezzi de Paula, Vanessa Capuano, Daniel Mendes Filho, Anna Cecília Dias Maciel Carneiro, Virgínia de Oliveira Crema, Lucas Felipe de Oliveira, Aldo Rogélis Aquiles Rodrigues, Nicola Montano, Valdo José Dias da Silva

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Abstract

Cardiomyopathy is a major outcome in patients with diabetes mellitus (DM) and contributes to the high morbidity/mortality observed in this disease. Aims To evaluate several biological properties of cardiac mesenchymal stem cells (cMSCs) in a rat model of streptozotocin-induced DM with concomitant diabetic cardiomyopathy. Main methods After 10 weeks of DM induction, diabetic and control rats were assessed using ECG and ventricular hemodynamics monitoring. Then, the hearts were excised and processed for histology and for extracting non-cardiomyocytic cells. A pool of these cells was plated for a colony forming units-fibroblasts (CFU-F) assay in order to estimate the number of cMSCs. The remaining cells were expanded to assess their proliferation rate as well as their osteogenic and adipogenic differentiation ability. Key findings DM rats presented intense hyperglycemia and changes in ECG, LV hemodynamic, cardiac mass index and fibrosis, indicating presence of DCM. The CFU-F assay revealed a higher number of cardiac CFU-Fs in DM rats (10.4 ± 1.1 CFU-F/105 total cells versus 7.6 ± 0.7 CFU-F/105 total cells in control rats, p < 0.05), which was associated with a significantly higher proliferative rate of cMSCs in DM rats. In contrast, cMSCs from DM rats presented a lower capacity to differentiate into both osteogenic (20.8 ± 4.2% versus 10.1 ± 1.0% in control rats, p < 0.05) and adipogenic lineages (4.6 ± 1.0% versus 1.3 ± 0.5% in control rats, p < 0.05). Significance The findings suggest, for the first time, that in chronic DM rats with overt DCM, cMSCs increase in number and exhibit changes in several functional properties, which could be implicated in the pathogenesis of diabetic cardiomyopathy.

Original languageEnglish
Pages (from-to)45-52
Number of pages8
JournalLife Sciences
Volume188
DOIs
Publication statusPublished - Nov 1 2017

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Keywords

  • Cardiac mesenchymal stem cells
  • Diabetes mellitus
  • Diabetic cardiomyopathy
  • Rats

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

de Paula, D. R. M., Capuano, V., Filho, D. M., Carneiro, A. C. D. M., de Oliveira Crema, V., de Oliveira, L. F., Rodrigues, A. R. A., Montano, N., & da Silva, V. J. D. (2017). Biological properties of cardiac mesenchymal stem cells in rats with diabetic cardiomyopathy. Life Sciences, 188, 45-52. https://doi.org/10.1016/j.lfs.2017.08.034