Research ArticleMultiple immunophenotypes of cardiac telocytes
Introduction
Telocytes (TCs) are described as interstitial cells with extremely long and thin prolongations, called telopodes (Tps) (www.telocytes.com). Tps have dilated portions (podoms) and very thin segments (podomeres), exhibiting moniliform appearance [1], [2]. These unique structural characteristics evoked substantial interest in terms of their functional significance [3], [4], [5], [6], [7], [8], [9]. However, dynamics of Tps extension, cell shape changes and adherence have not been well understood.
Cardiac TCs have been identified in epicardium [10], myocardium [11], endocardium [12], subendocardium [13], stem cell niches [14], myocardial sleeves [15] and heart valves [16]. They form an interstitial network that plays a very important role in heart development, renewal and repair [17], [18]. Intramyocardial transplantation of TCs has potential to reduce myocardial infarction and improve cardiac function in rats [19].
To date, specific molecular markers were not available to detect TCs, so morphology identification using transmission electron microscopy (TEM) remains as only firm diagnostic tool for detection of TCs [2], [20]. In this study, cardiac TCs were identified by light microscopy and scanning electron microscopy (SEM). The phenotype of TCs was characterized by CD34, c-kit, vimentin and caveolin-1 positivity [21]. TCs in different tissues display different phenotypes [22], [23]. Cardiac TCs express vimentin, CD34 and PDGFR-β [16]. The present study was to investigate dynamics of telopdes and features of their multiple immunophenotypes. The findings in this study may provide the direct evidence of the morphology of the cardiac TCs and a theoretical background to explain the role of TCs in heart development and myocardial repair following cardiac injury.
Section snippets
Animals
Neonatal Sprague-Dawley rats (1–3 day-old, 7.2±0.35 g, n=20) were utilized in this study. Animal treatment was performed according to the guidelines of The Ministry of Science and Technology of the People's Republic of China [(2006)398] and approved by the Xinxiang Medical University Animal Care Committee (No. 030032).
Isolation and culture of cardiac TCs
Cardiac TCs were isolated from neonatal rat hearts. Briefly, heart tissues were minced into small pieces of about 1 mm3 after washing with sterile phosphate-buffered saline (PBS).
Morphology of cardiac TCs
The isolated cells from rat hearts in suspension showed small and round shapes. Cardiac fibroblasts attached to the flasks after plating for 30–60 min, TCs attached after plating for 60–90 min, and cardiomyocytes attached after plating for 90 min by differential velocity adherence technique. Most of the attached cells were mainly cardiac fibroblasts and cardiomyocytes that presented spindle, oval and triangle shapes (Fig. 1). A few cells were TCs that exhibited small prominent body with 1–7 very
Discussion
TCs are novel type of interstitial cells that are dispersed in the connective tissues and form a three-dimensional network with endothelial cells, fibroblasts and other cells including cardiomyocytes [13]. It is known that cardiac TCs constitute approximately 1–1.5% of atrial myocardial volume [24]. The morphology of the cardiac TCs is different from cardiac fibroblasts and cadiomyocytes. TCs have a distinctive shape with a small pyriform, spindle or triangular body, as well as one or two oval
Conflicts of interest
The authors confirmed that there are no conflicts of interest.
Acknowledgments
We thank all members of our lab for sharing reagents and advice. This work was supported by a grant from the Brilliancy Talent Project of Henan Province (No. 084200510020), PR China.
References (31)
- et al.
Functional expression cloning of Nanog, a pluripotency sustaining embryonic stem cells
Cell
(2003) - et al.
The homeoprotein Nanog is required for maintenance of pluripoteney in mouse epiblast and ES cells
Cell
(2003) - et al.
Telocytes-a case of serendipity: the winding way from Interstitial Cells of Cajal (ICC), via Interstitial Cajal-Like Cells (ICLC) to Telocytes
J. Cell Mol. Med.
(2010) - et al.
Telocytes revisited
Biomol. Concepts
(2014) - et al.
Extracellular vesicles release by cardiac telocytes: electron microscopy and electron tomography
J. Cell. Mol. Med.
(2014) - et al.
Telocytes in human skin-are they involved in skin regeneration?
J. Cell. Mol. Med.
(2012) - et al.
Cardiac telocytes
Curr. Stem Cell Res. Ther.
(2015) - et al.
Telocytes subtypes in human urinary bladder
J. Cell Mol. Med.
(2014) - et al.
A loss of telocytes accompanies fibrosis of multiple organs in systemic sclerosis
J. Cell Mol. Med.
(2014) - et al.
Human resident CD34+ stromal cells/telocytes have progenitor capacity and are a source of αSMA+ cells during repair
Histol. Histopathol.
(2015)
Telocytes in liver regeneration: possible roles
J. Cell Mol. Med.
Epicardium-derived cells (EPDCs)in development, cardiac disease and repair of ischemia
J. Cell Mol. Med.
Telocytes as supporting cells for myocardial tissue organization in developing and adult heart
J. Cell Mol. Med.
Telocytes in endocardium: electron microscope evidence
J. Cell Mol. Med.
Telocytes form networks in normal cardiac tissues
Histol. Histopathol.
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