title: 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.
authors.affiliation: Biochemistry-Proteomics Department, Victor Babeş National Institute of Pathology, Bucharest, Romania.|National Institute for Chemical Pharmaceutical Research & Development, Bucharest, Romania.
authors.forename: Radu
authors.initials: R
authors.lastname: Albulescu
authors.affiliation: Biochemistry-Proteomics Department, Victor Babeş National Institute of Pathology, Bucharest, Romania.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Tanase
authors.affiliation: Biochemistry-Proteomics Department, Victor Babeş National Institute of Pathology, Bucharest, Romania.
authors.forename: Elena
authors.initials: E
authors.lastname: Codrici
authors.affiliation: Biochemistry-Proteomics Department, Victor Babeş National Institute of Pathology, Bucharest, Romania.
authors.forename: Daniela I
authors.initials: DI
authors.lastname: Popescu
authors.affiliation: Division of Cell Biology and Histology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.|Department of Ultrastructural Pathology, Victor Babeş National Institute of Pathology, Bucharest, Romania.
authors.forename: Sanda M
authors.initials: SM
authors.lastname: Cretoiu
authors.affiliation: Division of Cell Biology and Histology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.|Department of Advanced Studies, Victor Babeş National Institute of Pathology, Bucharest, Romania.
authors.forename: Laurentiu M
authors.initials: LM
authors.lastname: Popescu
mesh_terms: D016475:3T3 Cells; D000818:Animals; D030562:Databases, Protein; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032386:Myoblasts, Cardiac / Q000166:cytology / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000067170:Telocytes / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D020543:Proteome; D042461:Vascular Endothelial Growth Factor A
keywords: Luminex-xMAP; SELDI-TOF; cardiac stem cells; chemokines; cytokines; fibroblasts; growth factors; telocytes