Cardiac Telocytes 16 Years on—What Have We Learned So Far, and How Close Are We to Routine Application of the Knowledge in Cardiovascular Regenerative Medicine?

Abstract

The regeneration of a diseased heart is one of the principal challenges of modern cardiovascular medicine. There has been ongoing research on stem-cell-based therapeutic approaches. A cell population called telocytes (TCs) described only 16 years ago largely contributed to the research area of cardiovascular regeneration. TCs are cells with small bodies and extremely long cytoplasmic projections called telopodes, described in all layers of the heart wall. Their functions include cell-to-cell signaling, stem-cell nursing, mechanical support, and immunoregulation, to name but a few. The functional derangement or quantitative loss of TCs has been implicated in the pathogenesis of myocardial infarction, heart failure, arrhythmias, and many other conditions. The exact pathomechanisms are still unknown, but the loss of regulative, integrative, and nursing functions of TCs may provide important clues. Therefore, a viable avenue in the future modern management of these conditions is TC-based cell therapy. TCs have been previously transplanted into a mouse model of myocardial infarction with promising results. Tandem transplantation with stem cells may provide additional benefit; however, many underresearched areas need to be addressed in future research before routine application of TC-based cell therapy in human subjects. These include the standardization of protocols for isolation, cultivation, and transplantation, quantitative optimization of TC transplants, cost-effectivity analysis, and many others.

Scleroderma-like Impairment in the Network of Telocytes/CD34+ Stromal Cells in the Experimental Mouse Model of Bleomycin-Induced Dermal Fibrosis

“…Since the introduction of TCs/CD34 + stromal cells in the scientific literature in 2010, numerous efforts were made to inspect their existence and decipher their morphofunctional features in a variety of tissues/organs [3][4][5][6][7][8]11,12,42,43]. As a result, a growing body of evidence indicates that this long neglected, but definitely distinct, stromal cell population may greatly contribute to the shaping of the local tissue microenvironment in both health and disease [4,[6][7][8]12,[25][26][27][28]43].…”

“…Since TCs are considered central regulators of the local microenvironment by communicating with many different cell types through both direct intercellular contacts and release of paracrine factors [4,6,7,32,43], a loss of the complex telopode meshwork would inevitably result in disrupted intercellular signaling and, consequently, impaired tissue homeostasis. In this regard, it is worth noting that, at variance with control mouse skin, usually fibroblasts did not appear in contact with the telopodes of TCs in the fibrotic skin of bleomycin-treated mice.…”

Uterine Rat Telocyte Structure and Organization: An Immunohistochemical and Ultrastructural Study

“…Telocytes are also found in all of the heart's layers, including the epicardium, the endocardium and the myocardium. Telocytes are found throughout the reproductive system, including the prostate, testesuterus, myometrium and placenta [4][5][6][7][8][9][10][11][12].…”

The Potential of Berberine to Target Telocytes in Rabbit Heart

“…Immunohistochemistry, immunofluorescence, and scanning electron microscopy are used as auxiliary identification methods [1,2]. Importantly, TCs in the heart and blood vessels are double-positive immunostaining with CD34 and PDGFRα, including CD34 and c-kit/CD117 [5,6]. TCs are widely dispersed in various organs, especially in the heart.…”

“…TCs are widely dispersed in various organs, especially in the heart. Furthermore, several studies and reports exist regarding cardiac TCs [5,7]. Related studies have found that cardiac TCs are in contact with almost all cells in the heart (cardiomyocytes, endothelial cells, mast cells, etc.)…”