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

Abstract

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.

Dystrophin Deficiency Causes Progressive Depletion of Cardiovascular Progenitor Cells in the Heart

“…With ageing, we observed a depletion of CVPC population, consistent with the decrease of the progenitor cells in dystrophin-deficient skeletal muscle [ 20 ]. Therefore, although CVPCs and satellite cells have different functions, our findings likely reveal a common phenomenon involving an early-stage recruitment triggered by cardiac injury as also previously shown [ 34 , 52 ], but followed by rapid depletion of the CVPC pool. We summarize our findings and a proposed mechanism of the CVPC in the dystrophin-deficient heart in the diagram of Figure 7 .…”

Muscle stem cell and physical activity: what point is the debate at?

“…Although the principal player of cardiac hypertrophy is the enlargement of differentiated cardiomyocytes, Leite et al [102] recently demonstrated that also c-kit + cardiac stem cells (CSC) participate to cardiac hypertrophy generated by physical exercise. c-Kit + CSC have been first reviewed 10 years ago [103].…”

Pathological Left Ventricular Hypertrophy and Stem Cells: Current Evidence and New Perspectives

“…CSCs include, among others, c-kit + Lin − and Sca-1 + -Lin − cells, Isl-1 progenitors, epicardial progenitors, and progenitors generating cardiospheres and muscle-derived mesenchymal stem cells. Experimental studies have shown that it is mostly c-kit + Lin − cells that seem to increase in the heart in response to exercise training [ 5 ]. However, it has been speculated that Sca-1 + -Lin − might also be stimulated in physiological hypertrophy.…”