Science China Life Sciences

, Volume 57, Issue 2, pp 241–247 | Cite as

Distribution and characteristics of telocytes as nurse cells in the architectural organization of engineered heart tissues

  • Jin Zhou
  • Yan Wang
  • Ping Zhu
  • HongYu Sun
  • YongChao Mou
  • CuiMi Duan
  • AnNing Yao
  • ShuangHong Lv
  • ChangYong Wang
Open Access
Research Paper Thematic Issue: Stem Cells and Regenerative Medicine in China

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.

Keywords

telocytes collagen/matrigel scaffolds engineered heart tissues reconstruction 

References

  1. 1.
    Thuneberg L. Interstitial cells of Cajal: intestinal pacemaker cells? Adv Anat Embryol Cell Biol, 1982, 71: 1–130PubMedCrossRefGoogle Scholar
  2. 2.
    Faussone-Pellegrini MS, Thuneberg L. Guide to the identification of interstitial cells of Cajal. Microsc Res Tech, 1999, 47: 248–266PubMedCrossRefGoogle Scholar
  3. 3.
    Popescu LM, Ciontea SM, Cretoiu D. Interstitial Cajal-like cells in human uterus and fallopian tube. Ann NY Acad Sci, 2007, 1101: 139–165PubMedCrossRefGoogle Scholar
  4. 4.
    Popescu LM, Hinescu ME, Ionescu N, Ciontea SM, Cretoiu D, Ardelean C. Interstitial cells of Cajal in pancreas. J Cell Mol Med, 2005, 9: 169–190PubMedCrossRefGoogle Scholar
  5. 5.
    Hinescu ME, Ardeleanu C, Gherghiceanu M, Popescu LM. Interstitial Cajal-like cells in human gallbladder. J Mol Histol, 2007, 38: 275–284PubMedCrossRefGoogle Scholar
  6. 6.
    Lang RJ, Klemm MF. Interstitial cell of Cajallike cells in the upper urinary tract. J Cell Mol Med, 2005, 9: 543–556PubMedCrossRefGoogle Scholar
  7. 7.
    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: 689–694PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    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: 479–523PubMedCrossRefGoogle Scholar
  9. 9.
    Hinescu ME, Popescu LM. Interstitial Cajallike cells (ICLC) in human atrial myocardium. J Cell Mol Med, 2005, 9: 972–975PubMedCrossRefGoogle Scholar
  10. 10.
    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: 729–740PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Sucin L, Nicolescu MI, Popescu LM. Cardiac telocytes: serial dynamic images in cell culture. J Cell Mol Med, 2010, 14: 2687–2692CrossRefGoogle Scholar
  12. 12.
    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: 243–257PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    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: 771–777PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Gherghiceanu M, Popescu LM. Human epicardium: ultrastructural ancestry of mesothelium and mesenchymal cells. J Cell Mol Med, 2009, 13: 2949–2951PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Gherghiceanu M, Manole CG, Popescu LM. Telocytes in endocardium: electron microscope evidence. J Cell Mol Med, 2010, 14: 2330PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Gherghiceanu M, Popescu LM. Cardiomyocyte precursors and telocytes in epicardial stem cell niche: electron microscope images. J Cell Mol Med, 2010, 14: 871–877PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    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: 866–886PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    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: 2531–2538PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Faussone-Pellegrini MS, Bani D. Relationships between telocytes and cardiomyocytes during pre- and post-natal life. J Cell Mol Med, 2010, 14: 1061–1063PubMedPubMedCentralGoogle Scholar
  20. 20.
    Franchini JL, Propst JT, Comer GR, Yost MJ. Novel tissue engineered tubular heart tissue for in vitro pharmaceutical toxicity testing. Microsc Microanal, 2007, 13: 267–271PubMedCrossRefGoogle Scholar
  21. 21.
    Bursac N, Loo Y, Leong K, Tung L. Novel anisotropic engineered cardiac tissues: studies of electrical propagation. Biochem Biophys Res Commun, 2007, 361: 847–853PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    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: e9275PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    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: 106–114PubMedCrossRefGoogle Scholar
  24. 24.
    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: 223–230PubMedCrossRefGoogle Scholar
  25. 25.
    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: 1091–1097PubMedCrossRefGoogle Scholar
  26. 26.
    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: 2229–2237PubMedCrossRefGoogle Scholar
  27. 27.
    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: 2641–2645PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Loewenstein WR. Junctional intercellular communication: the cell-to-cell membrane channel. Physiol Rev, 1981, 61: 829–913PubMedGoogle Scholar
  29. 29.
    Musil LS, Goodenough DA. Gap junctional intercellular communication and the regulation of connexin expression and function. Curr Opin Cell Biol, 1990, 2: 875–880PubMedCrossRefGoogle Scholar
  30. 30.
    Li J, Radice GL. A new perspective on intercalated disc organization: implications for heart disease. Dermatol Res Pract, 2010, 2010: 207835PubMedPubMedCentralGoogle Scholar
  31. 31.
    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: 63–77CrossRefGoogle Scholar
  32. 32.
    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: 495–502CrossRefGoogle Scholar
  33. 33.
    Ottaviano FG, Yee KO. Communication signals between cardiac fibroblasts and cardiac myocytes. J Cardiovasc Pharmacol, 2011, 57: 513–521PubMedCrossRefGoogle Scholar

Copyright information

© The Author(s) 2014

Authors and Affiliations

  • Jin Zhou
    • 1
  • Yan Wang
    • 1
  • Ping Zhu
    • 2
  • HongYu Sun
    • 1
  • YongChao Mou
    • 1
  • CuiMi Duan
    • 1
  • AnNing Yao
    • 1
  • ShuangHong Lv
    • 1
    • 3
  • ChangYong Wang
    • 1
  1. 1.Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research CenterAcademy of Military Medical SciencesBeijingChina
  2. 2.The First Department of Cardiology, South BuildingThe General Hospital of People’s Liberation ArmyBeijingChina
  3. 3.Laboratory of OncologyAffiliated Hospital of Academy of Military Medical SciencesBeijingChina

Personalised recommendations