**5.1 Cardiac telocytes in heart development and physiological growth**

Involvement of cardiac TCs and cardiomyocytes during development have been investigated using myocardium from embryonic (E14, E17), newborn (P0, P6), and adult (2 months) CD1 mice by using transmission electron microscopy and immunohistochemistry [110]. It was found that TCs were present from early embryonic to adult life in the mouse heart [110]. Besides, cardiac TCs demonstrated immature features in early embryonic hearts while cardiac TCs exhibit a more differentiated phenotype in newborn hearts [110]. Cardiac TCs played a fundamental role during cardiac development by forming a correct three-dimensional myocardial architecture and nursing cardiomyocyte precursors [110]. Intriguingly, cardiac TCs were found negative for c-kit and CD34 during the embryonic stage [110]; however, CD34 was expressed in a few TCs in the heart of a newborn mouse, and in most TCs in adult hearts [110]. This suggests a phenotype switch of cardiac TCs during development.

Exercise can induce cardiac physiological growth, which is characterized by increased cell size of cardiomyocytes and the formation of new cardiomyocytes [111, 112]. Three double-immunostainings, including CD34/PDGFR-ɑ, CD34/ PDGFR-ß-, and CD34/vimentin, have been used to determine the number of cardiac TCs in exercise-induced physiological cardiac growth [81]. The number of cardiac TCs was found to be significantly increased in the exercised heart [81]. The increased cardiac TCs in exercise might communicate with cardiomyocytes through direct contacts or telocyte-shed vesicles, balance angiogenesis, and maintain the normal 3D-organization of ECM [81]. This study suggested a potential role of cardiac TCs in exercise-induced cardiac growth [81].
