Abstract
Interstitial Cajal-like cells are a distinct type of interstitial cell with a wide distribution in mammalian organs and tissues, and have been given the name “telocytes”. Recent studies have demonstrated the potential roles of telocytes in heart development, renewal, and repair. However, further research on the functions of telocytes is limited by the complicated in vivo environment. This study was designed to construct engineered heart tissue (EHT) as a three-dimensional model in vitro to better understand the role of telocytes in the architectural organization of the myocardium. EHTs were constructed by seeding neonatal cardiomyocytes in collagen/Matrigel scaffolds followed by culture under persistent static stretch. Telocytes in EHTs were identified by histology, toluidine blue staining, immunofluorescence, and transmission electron microscopy. The results from histology and toluidine blue staining demonstrated widespread putative telocytes with compact toluidine blue-stained nuclei, which were located around cardiomyocytes. Prolongations from the cell bodies showed a characteristic dichotomous branching pattern and formed networks in EHTs. Immunofluorescence revealed positive staining of telocytes for CD34 and vimentin with typical moniliform prolongations. A series of electron microscopy images further showed that typical telocytes embraced the cardiomyocytes with their long prolongations and exhibited a marked appearance of nursing cardiomyocytes during the construction of EHTs. This finding highlights the great importance of telocytes in the architectural organization of EHTs. It also suggests that EHT is an appropriate physical and pathological model system in vitro to study the roles of telocytes during heart development and regeneration.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Thuneberg L. Interstitial cells of Cajal: intestinal pacemaker cells? Adv Anat Embryol Cell Biol, 1982, 71: 1–130
Faussone-Pellegrini MS, Thuneberg L. Guide to the identification of interstitial cells of Cajal. Microsc Res Tech, 1999, 47: 248–266
Popescu LM, Ciontea SM, Cretoiu D. Interstitial Cajal-like cells in human uterus and fallopian tube. Ann NY Acad Sci, 2007, 1101: 139–165
Popescu LM, Hinescu ME, Ionescu N, Ciontea SM, Cretoiu D, Ardelean C. Interstitial cells of Cajal in pancreas. J Cell Mol Med, 2005, 9: 169–190
Hinescu ME, Ardeleanu C, Gherghiceanu M, Popescu LM. Interstitial Cajal-like cells in human gallbladder. J Mol Histol, 2007, 38: 275–284
Lang RJ, Klemm MF. Interstitial cell of Cajallike cells in the upper urinary tract. J Cell Mol Med, 2005, 9: 543–556
McHale NG, Hollywood MA, Sergeant GP, Shafei M, Thornbury KT, Ward SM. Organization and function of ICC in the urinary tract. J Physiol, 2006, 576: 689–694
Hinescu ME, Radu E, Ionescu N, Ceausu M, Gherghiceanu M, Braga RI, Vasilescu F, Zagrean L, Ardeleanu C. Novel type of interstitial cell (Cajal-like) in human fallopian tube. J Cell Mol Med, 2005, 9: 479–523
Hinescu ME, Popescu LM. Interstitial Cajallike cells (ICLC) in human atrial myocardium. J Cell Mol Med, 2005, 9: 972–975
Popescu LM, Faussone-Pellegrini MS. 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, 14: 729–740
Sucin L, Nicolescu MI, Popescu LM. Cardiac telocytes: serial dynamic images in cell culture. J Cell Mol Med, 2010, 14: 2687–2692
Hinescu ME, Gherghiceanu M, Mandache E, Ciontea SM, Popescu LM. Interstitial Cajal-like cells (ICLC) in atrial myocardium: ultrastructural and immunohistochemical characterization. J Cell Mol Med, 2006, 10: 243–257
Suciu L, Popescu LM, Regalia T, Ardelean A, Manole CG. Epicardium: interstitial Cajal-like cells (ICLC) highlighted by immunofluorescence. J Cell Mol Med, 2009, 13: 771–777
Gherghiceanu M, Popescu LM. Human epicardium: ultrastructural ancestry of mesothelium and mesenchymal cells. J Cell Mol Med, 2009, 13: 2949–2951
Gherghiceanu M, Manole CG, Popescu LM. Telocytes in endocardium: electron microscope evidence. J Cell Mol Med, 2010, 14: 2330
Gherghiceanu M, Popescu LM. Cardiomyocyte precursors and telocytes in epicardial stem cell niche: electron microscope images. J Cell Mol Med, 2010, 14: 871–877
Popescu LM, Gherghiceanu M, Manole CG, Faussone-Pellegrini MS. Cardiac renewing: interstitial Cajal-like cells nurse cardiomyocyte progenitors in epicardial stem cell niches. J Cell Mol Med, 2009, 13: 866–886
Bani D, Formigli L, Gherghiceanu M, Faussone-Pellegrini MS. Telocytes as supporting cells for myocardial tissue organization in developing and adult heart. J Cell Mol Med, 2010, 14: 2531–2538
Faussone-Pellegrini MS, Bani D. Relationships between telocytes and cardiomyocytes during pre- and post-natal life. J Cell Mol Med, 2010, 14: 1061–1063
Franchini JL, Propst JT, Comer GR, Yost MJ. Novel tissue engineered tubular heart tissue for in vitro pharmaceutical toxicity testing. Microsc Microanal, 2007, 13: 267–271
Bursac N, Loo Y, Leong K, Tung L. Novel anisotropic engineered cardiac tissues: studies of electrical propagation. Biochem Biophys Res Commun, 2007, 361: 847–853
Katare RG, Ando M, Kakinuma Y, Sato T. Engineered heart tissue: a novel tool to study the ischemic changes of the heart in vitro. PLoS ONE, 2010, 5: e9275
Zimmermann WH, Fink C, Kralisch D, Remmers U, Weil J, Eschenhagen T. Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes. Biotechnol Bioeng, 2000, 68: 106–114
Zimmermann WH, Schneiderbanger K, Schubert P, Didié M, Münzel F, Heubach JF, Kostin S, Neuhuber WL, Eschenhagen T. Tissue engineering of a differentiated cardiac muscle construct. Circ Res, 2002, 90: 223–230
Zhao YS, Wang CY, Li DX, Zhang XZ, Qiao Y, Guo XM, Wang XL, Dun CM, Dong LZ, Song Y. Construction of a unidirectionally beating 3-dimensional cardiac muscle construct. J Heart Lung Transplant, 2005, 24: 1091–1097
Guo XM, Zhao YS, Chang HX, Wang CY, E LL, Zhang XA, Duan CM, Dong LZ, Jiang H, Li J, Song Y, Yang XJ. Creation of engineered cardiac tissue in vitro from mouse embryonic stem cells. Circulation, 2006, 113: 2229–2237
Zhou J, Zhang Y, Wen X, Cao J, Li D, Lin Q, Wang H, Liu Z, Duan C, Wu K, Wang C. Telocytes accompanying cardiomyocyte in primary culture: two- and three-dimensional culture environment. J Cell Mol Med, 2010, 14: 2641–2645
Loewenstein WR. Junctional intercellular communication: the cell-to-cell membrane channel. Physiol Rev, 1981, 61: 829–913
Musil LS, Goodenough DA. Gap junctional intercellular communication and the regulation of connexin expression and function. Curr Opin Cell Biol, 1990, 2: 875–880
Li J, Radice GL. A new perspective on intercalated disc organization: implications for heart disease. Dermatol Res Pract, 2010, 2010: 207835
Faussone-Pellegrini MS, Bani D. Cordial connections: molecular ensembles and structures of adhering junctions connecting interstitial cells of cardiac valves in situ and in cell culture. Cell Tissue Res, 2009, 337: 63–77
Li J, Radice GL. Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF168. Nat Med, 1999, 5: 495–502
Ottaviano FG, Yee KO. Communication signals between cardiac fibroblasts and cardiac myocytes. J Cardiovasc Pharmacol, 2011, 57: 513–521
Author information
Authors and Affiliations
Corresponding authors
Additional information
Contributed equally to this work
This article is published with open access at springerlink.bibliotecabuap.elogim.com
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Zhou, J., Wang, Y., Zhu, P. et al. Distribution and characteristics of telocytes as nurse cells in the architectural organization of engineered heart tissues. Sci. China Life Sci. 57, 241–247 (2014). https://doi.org/10.1007/s11427-013-4602-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-013-4602-1