Endogenous resident c-Kit cardiac stem cells increase in mice with an exercise-induced, physiologically hypertrophied heart

• Published in: Stem cell research Vol. 15; no. 1; pp. 151 - 164
• Main Authors: Leite, Camila Ferreira, Lopes, Carolina Salomão, Alves, Angélica Cristina, Fuzaro, Caroline Santos Capitelli, Silva, Marcos Vinícius, Oliveira, Lucas Felipe de, Garcia, Lidiane Pereira, Farnesi, Thaís Soares, Cuba, Marília Beatriz de, Rocha, Lenaldo Branco, Rodrigues, Virmondes, Oliveira, Carlo José Freire de, Dias da Silva, Valdo José
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01-07-2015; Elsevier
• Subjects: Animals; Cardiomegaly - diagnostic imaging; Cardiomegaly - pathology; Cardiomegaly - physiopathology; Cell Adhesion; Cell Count; Colony-Forming Units Assay; Flow Cytometry; Green Fluorescent Proteins - metabolism; Male; Mice, Inbred C57BL; Mice, Transgenic; Myocardium - pathology; Physical Conditioning, Animal; Physical Endurance; Proto-Oncogene Proteins c-kit - metabolism; Stem Cells - cytology; Stem Cells - metabolism; Stromal Cells - cytology; Swimming; Ultrasonography; Ventricular Remodeling
• ISSN: 1873-5061; 1876-7753
• DOI: 10.1016/j.scr.2015.05.011

Physical activity evokes well-known adaptations in the cardiovascular system. Although exercise training induces cardiac remodeling, whether multipotent stem cells play a functional role in the hypertrophic process remains unknown. To evaluate this possibility, C57BL/6 mice were subjected to swimming training aimed at achieving cardiac hypertrophy, which was morphologically and electrocardiographically characterized. Subsequently, c-Kit+Lin− and Sca-1+Lin− cardiac stem cells (CSCs) were quantified using flow cytometry while cardiac muscle-derived stromal cells (CMSCs, also known as cardiac-derived mesenchymal stem cells) were assessed using in vitro colony-forming unit fibroblast assay (CFU-F). Only the number of c-Kit+Lin− cells increased in the hypertrophied heart. To investigate a possible extracardiac origin of these cells, a parabiotic eGFP transgenic/wild-type mouse model was used. The parabiotic pairs were subjected to swimming, and the wild-type heart in particular was tested for eGFP+ stem cells. The results revealed a negligible number of extracardiac stem cells in the heart, allowing us to infer a cardiac origin for the increased amount of detected c-Kit+ cells. In conclusion, the number of resident Sca-1+Lin− cells and CMSCs was not changed, whereas the number of c-Kit+Lin− cells was increased during physiological cardiac hypertrophy. These c-Kit+Lin− CSCs may contribute to the physiological cardiac remodeling that result from exercise training.
•The focus was on the involvement of stem cells in the physiological cardiac hypertrophy induced by exercise training.•The number of c-Kit+Lin− cardiac stem cells increases during the physiological cardiac remodeling.•The number of Sca-1+Lin− cardiac stem cells and cardiac muscle-derived stromal cells is not modified in the process.•Extracardiac stem cells are minimally recruited to the heart.