**5. Heart**

Cardiac TCs are among the most well described in the body [101]. Cardiac TCs are unique interstitial cells in the heart [101]. Intramyocardial TCs account for less than 1% of interstitial cells in the human heart [56]. Cardiac TCs have been identified in heart valves, left and right atrium and ventricle, epicardium, myocardium, endocardium, sub-endocardium, and myocardial sleeves [101, 102], in mice, rat, porcine, and human [56, 103]. The whole ultrastructural anatomy of human cardiac TCs has been reconstructed by focused ion beam scanning electron microscopy (FIB-SEM) [104]. The electrophysiology of human cardiac atrial and ventricular TCs has also been reported [105].

Cardiac TCs are completely different from other types of myocardial interstitial cells, especially from cardiac fibroblasts [106]. Cardiac TCs and cardiac fibroblasts are completely different in immunophenotypes, as cardiac TCs are positive for CD34/ PDGFR-ɑ, CD34/PDGFR-ß, or CD34/Vimentin while cardiac fibroblasts are only positive for PDGFR-ß and Vimentin [106]. CD34/PDGFR-ɑ positive TCs account for one-third of the total cells among TCs enriched rat cardiac interstitial cell population [106, 107]. Some studies have also reported that cardiac TCs inconstantly express CD34/c-kit [56]. Besides, cardiac TCs are also distinct from pericytes, since cardiac TCs are CD34 positive and ɑ-SMA weak positive while pericytes are CD34 negative and ɑ-SMA positive [106]. Moreover, cardiac TCs are CD34/PDGFR-ß positive while pericytes are CD34 negative and PDGFR-ß positive [106]. Interestingly, cardiac TCs are positive for CD29 (a mesenchymal marker) but negative for CD45 (a hematopoietic marker), suggesting that cardiac TCs could be a source of cardiac mesenchymal cells [106]. Interestingly, the telomerase concentration in CD117 and CD34 positive cardiac TCs is significantly higher than that in cardiomyocytes and is 2.5-times and 1.5 times lower than that in bone mesenchymal stem cells and cardiac fibroblasts [108].

Cardiac TCs can form tight junctions with all other types of cells within the heart including cardiomyocytes, vascular smooth muscle cells, endothelial cells, and pericytes. The functions of cardiac TCs are not fully known but are proposed as follows: (1) intercellular signaling; (2) mechanoreceptors/transducers; and (3) cardiac homeostasis and repair [101, 109]. In the heart, telocytes participate in cardiac development and physiology, and diverse cardiovascular diseases (**Figure 7**).

### **Figure 7.**

*Cardiac telocytes are in tandem with different types of cells in the heart, and participate in cardiac development and physiology, and diverse cardiovascular diseases. ECM, extracellular matrix; VSMCs, vascular smooth muscle cells.*

**83**

*Telocytes: New Connecting Devices in the Stromal Space of Organs*

cardiac TCs in exercise-induced cardiac growth [81].

**5.2 Cardiac telocytes in cardiovascular diseases**

myocardial fibrosis caused by systemic sclerosis.

collagens and positively with degraded collagens [52].

**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

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

Isolated atrial amyloidosis (IAA) is frequently found in long-standing atrial fibrillation patients [113]. By electron microscopy, telopodes are found surrounding the amyloid deposits, which limit their spreading into the interstitium [113]. This indicates that TCs might participate in amyloidogenesis by gathering masses of

Systemic sclerosis represents a complex connective tissue disease featured with

The imbalance between cardiac TCs apoptotic death and cardiac TCs proliferation is responsible for the depletion of cardiac TCs in cardiac diseases leading to heart failure [52]. In human heart failure patients' myocardium, the number of cardiac TCs and telopodes decreases over twofold. Additionally, the apoptotic cardiac TCs increases threefold in the diseased heart while the percentage of proliferating cardiac TCs remains unchanged, suggesting that the decreased cardiac TCs population in heart failure is mainly due to increased apoptosis [52]. Interestingly, the number of cardiac TCs and telopodes has been found to depend on the composition of the extracellular matrix which is correlated negatively with mature fibrillar

The changes of cardiac TCs have been determined in an acute myocardial infarction rat model induced by isoproterenol (ISO) [114]. It was found that CD117/CD34 positive cardiac TCs were undetectable with immunohistochemical

fibrosis of the skin and various internal organs [54]. TCs, as defined by CD34 positivity/CD31-negativity, were checked in the fibrotic areas of systemic sclerosis myocardium and were found to be almost undetectable [54]. However, in the control myocardium, numerous TCs were found located in the interstitium surrounding cardiomyocytes [54]. This indicates that loss of cardiac TCs contributes to

*DOI: http://dx.doi.org/10.5772/intechopen.89383*

development.

amyloid fibrils.

*Innovations in Cell Research and Therapy*

TCs has also been reported [105].

Cardiac TCs are among the most well described in the body [101]. Cardiac TCs are unique interstitial cells in the heart [101]. Intramyocardial TCs account for less than 1% of interstitial cells in the human heart [56]. Cardiac TCs have been identified in heart valves, left and right atrium and ventricle, epicardium, myocardium, endocardium, sub-endocardium, and myocardial sleeves [101, 102], in mice, rat, porcine, and human [56, 103]. The whole ultrastructural anatomy of human cardiac TCs has been reconstructed by focused ion beam scanning electron microscopy (FIB-SEM) [104]. The electrophysiology of human cardiac atrial and ventricular

Cardiac TCs are completely different from other types of myocardial interstitial cells, especially from cardiac fibroblasts [106]. Cardiac TCs and cardiac fibroblasts are completely different in immunophenotypes, as cardiac TCs are positive for CD34/ PDGFR-ɑ, CD34/PDGFR-ß, or CD34/Vimentin while cardiac fibroblasts are only positive for PDGFR-ß and Vimentin [106]. CD34/PDGFR-ɑ positive TCs account for one-third of the total cells among TCs enriched rat cardiac interstitial cell population [106, 107]. Some studies have also reported that cardiac TCs inconstantly express CD34/c-kit [56]. Besides, cardiac TCs are also distinct from pericytes, since cardiac TCs are CD34 positive and ɑ-SMA weak positive while pericytes are CD34 negative and ɑ-SMA positive [106]. Moreover, cardiac TCs are CD34/PDGFR-ß positive while pericytes are CD34 negative and PDGFR-ß positive [106]. Interestingly, cardiac TCs are positive for CD29 (a mesenchymal marker) but negative for CD45 (a hematopoietic marker), suggesting that cardiac TCs could be a source of cardiac mesenchymal cells [106]. Interestingly, the telomerase concentration in CD117 and CD34 positive cardiac TCs is significantly higher than that in cardiomyocytes and is 2.5-times and 1.5 times lower than that in bone mesenchymal stem cells and cardiac fibroblasts [108]. Cardiac TCs can form tight junctions with all other types of cells within the heart including cardiomyocytes, vascular smooth muscle cells, endothelial cells, and pericytes. The functions of cardiac TCs are not fully known but are proposed as follows: (1) intercellular signaling; (2) mechanoreceptors/transducers; and (3) cardiac homeostasis and repair [101, 109]. In the heart, telocytes participate in cardiac development and physiology, and diverse cardiovascular diseases (**Figure 7**).

*Cardiac telocytes are in tandem with different types of cells in the heart, and participate in cardiac development and physiology, and diverse cardiovascular diseases. ECM, extracellular matrix; VSMCs,* 

**5. Heart**

**82**

**Figure 7.**

*vascular smooth muscle cells.*
