The secretome of myocardial telocytes modulates the activity of cardiac stem cells

Abstract

Telocytes (TCs) are interstitial cells that are present in numerous organs, including the heart interstitial space and cardiac stem cell niche. TCs are completely different from fibroblasts. TCs release extracellular vesicles that may interact with cardiac stem cells (CSCs) via paracrine effects. Data on the secretory profile of TCs and the bidirectional shuttle vesicular signalling mechanism between TCs and CSCs are scarce. We aimed to characterize and understand the in vitro effect of the TC secretome on CSC fate. Therefore, we studied the protein secretory profile using supernatants from mouse cultured cardiac TCs. We also performed a comparative secretome analysis using supernatants from rat cultured cardiac TCs, a pure CSC line and TCs-CSCs in co-culture using (i) high-sensitivity on-chip electrophoresis, (ii) surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and (iii) multiplex analysis by Luminex-xMAP. We identified several highly expressed molecules in the mouse cardiac TC secretory profile: interleukin (IL)-6, VEGF, macrophage inflammatory protein 1α (MIP-1α), MIP-2 and MCP-1, which are also present in the proteome of rat cardiac TCs. In addition, rat cardiac TCs secrete a slightly greater number of cytokines, IL-2, IL-10, IL-13 and some chemokines like, GRO-KC. We found that VEGF, IL-6 and some chemokines (all stimulated by IL-6 signalling) are secreted by cardiac TCs and overexpressed in co-cultures with CSCs. The expression levels of MIP-2 and MIP-1α increased twofold and fourfold, respectively, when TCs were co-cultured with CSCs, while the expression of IL-2 did not significantly differ between TCs and CSCs in mono culture and significantly decreased (twofold) in the co-culture system. These data suggest that the TC secretome plays a modulatory role in stem cell proliferation and differentiation.

Ultrastructural and immunohistochemical characteristics of telocytes in the skin and skeletal muscle of newborn rats

“…Note the presence of other telopods (Tp) C. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.) (TEM A, C X2000, B X2500) TCs and this might indicate a mandatory cooperation during the recruitment and differentiation processes TCs may have an important role in helping the differentiation and migration of stem cells as they can deliver signals to stem cells to differentiate Albulescu et al, 2015). In addition, they might play a role in the process of repair or regeneration by increasing the efficiency of collagen fiber and fibroblasts Bei et al, 2015).…”

Expression of toll‐like receptors and their regulatory roles in murine cardiac telocytes

“…Presumably, this support might contribute to tissue homeostasis, regeneration or repair and transmission of intercellular signals . Ultrastructural evidence showed that telocytes were spatially close not only to capillaries, nerve fibres, myocytes, smooth muscle cells and stem cells but also to macrophages, mast cells, eosinophils and lymphocytes . Telocytes might modulate the immunocytes through direct synapse‐like contact or indirect paracrine communication by secreting soluble mediators, such as IL‐6, VEGF and nitric oxide .…”

“…Ultrastructural evidence showed that telocytes were spatially close not only to capillaries, nerve fibres, myocytes, smooth muscle cells and stem cells but also to macrophages, mast cells, eosinophils and lymphocytes . Telocytes might modulate the immunocytes through direct synapse‐like contact or indirect paracrine communication by secreting soluble mediators, such as IL‐6, VEGF and nitric oxide . Although telocytes were reported to be involved in multiple autoimmune, inflammatory and fibrotic disorders, their number was decreased and their morphology was disrupted in these conditions .…”

Increased telocytes involved in the proliferation of vascular smooth muscle cells in rat carotid artery balloon injury

“…Other studies have reported that TCs can secrete certain cytokines, including VEGF (vascular endothelial growth factor), IL-6 (interleukin-6), MIP-1α (macrophage inflammatory protein 1-α), thus playing a modulatory role in stem cell proliferation and differentiation (Albulescu et al, 2015) or promoting the proliferation and angiogenesis of human pulmonary microvascular endothelial cells . This study showed that the ratio of VSMCs in S and G2/M phase increased when VSMCs were incubated with the supernatant of TCs.…”