Skip to main content
Log in

Characterization of Tunneling Nanotubes in Wharton’s jelly Mesenchymal Stem Cells. An Intercellular Exchange of Components between Neighboring Cells

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

Intercellular communication is one of the most important events in cell population behavior. In the last decade, tunneling nanotubes (TNTs) have been recognized as a new form of long distance intercellular connection. TNT function is to allow molecular and subcellular structure exchange between neighboring cells via the transfer of molecules and organelles such as calcium ions, prions, viral and bacterial pathogens, small lysosomes and mitochondria. New findings support the concept that mesenchymal stem cells (MSCs) can affect cell microenvironment by the release of soluble factors or the transfer of cellular components to neighboring cells, in a way which significantly contributes to cell regulation and tissue repair, although the underlying mechanisms remain poorly understood. MSCs have many advantages for their implementation in regenerative medicine. The TNTs in these cell types are heterogeneous in both structure and function, probably due to their highly dynamic behavior. In this work we report an extensive and detailed description of types, structure, components, dynamics and functionality of the TNTs bridging neighboring human umbilical cord MSCs obtained from Wharton”s jelly. Characterization studies were carried out through phase contrast, fluorescence, electron microscopy and time lapse images with the aim of describing cells suitable for an eventual regenerative medicine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Rustom, A., Saffrich, R., Markovic, I., Walther, P., & Gerdes, H. H. (2004). Nanotubular highways for intercellular organelle transport. Science, 303, 1007–1010.

    Article  CAS  PubMed  Google Scholar 

  2. Watkins, S. C., & Salter, R. D. (2005). Functional connectivity between immune cells mediated by tunneling nanotubes. Immunity, 23, 309–318.

    Article  CAS  PubMed  Google Scholar 

  3. Koyanagi, M., Brandes, R. P., Haendeler, J., Zeiher, A. M., & Dimmeler, S. (2005). Cell-to-cell connection of endothelial progenitor cells with cardiac myocytes by nanotubes: a novel mechanism for cell fate changes? Circulation Research, 96, 1039–1041.

    Article  CAS  PubMed  Google Scholar 

  4. Önfelt, B., Nedvetzki, S., Benninger, R. K., Purbhoo, M. A., Sowinski, S., Hume, A. N., Seabra, M. C., Neil, M. A., French, P. M., & Davis, D. M. (2006). Structurally distinct membrane nanotubes between human macrophages support long-distance vesicular traffic or surfing of bacteria. Journal of Immunology, 177, 8476–8483.

    Article  Google Scholar 

  5. Plotnikov, E. Y., Khryapenkov, T. G., Galkina, S., Sukhikhb, G., & Zorova, D. (2010). Cytoplasm and organelletransfer between mesenchymal multipotent stromal cells and renal tubular cells in co-culture. Experimental Cell Research, 316, 2447–2455.

    Article  CAS  PubMed  Google Scholar 

  6. Gerdes, H. H., & Carvalho, R. (2008). Intercellular transfer mediated by tunneling nanotubes. Current Opinion in Cell Biology, 20, 470–475.

    Article  CAS  PubMed  Google Scholar 

  7. Sisakhtnezhad, S., & Khosravi, L. (2015). Emerging physiological and pathological implications of tunneling nanotubes formation between cells. European Journal of Cell Biology, 94, 429–443.

    Article  CAS  PubMed  Google Scholar 

  8. Gerdes, H., Bukoreshtliev, N., & Barroso, J. (2007). Tunneling nanotubes: a new route for the exchange of components between animal cells. FEBS Letters, 581, 2194–2201.

    Article  CAS  PubMed  Google Scholar 

  9. Yasuda, K., Khandare, A., Burianovsky, L., Maruyama, S., Zhang, F., Nasjletti, A., & Goligorsky, M. (2011). Tunneling nanotubes mediate rescue of prematurely senescent endothelial cells by endothelial progenitors: exchange of lysosomal pool. Aging, 3, 597–608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Carvalho, M., Teixeira, F., Reis, R., Sousa, N., & Salgado, A. (2011). Mesenchymal stem cells in the umbilical cord: phenotypic characterization, secretome and applications in central nervous system regenerative medicine. Current Stem Cell Research & Therapy, 6, 221–228.

    Article  CAS  Google Scholar 

  11. Batsali, A. K., Kastrinaki, M. C., Papadaki, H. A., & Pontikoglou, C. (2013). Mesenchymal stem cells derived from Wharton's jelly of the umbilical cord: biological properties and emerging clinical applications. Current Stem Cell Research & Therapy, 8, 144–155.

    Article  CAS  Google Scholar 

  12. Luzzani, C., Neiman, G., Garate, X., Questa, M., Solari, C., Fernandez-Espinosa, D., García, M., Errecalde, A., Guberman, A., Scassa, M. E., Sevlever, G. E., Romorini, L., & Miriuka, S. G. (2015). A therapy-grade protocol for differentiation of pluripotent stem cells into mesenchymal stem cells using platelet lysate as supplement. Stem Cell Research & Therapy, 6, 6 .http://stemcellres.com/content/6/1/6

    Article  Google Scholar 

  13. Noble, C., Nilsson, A., Freitag, C., Beech, J., Tegenfeldt, J., & Ambjörnsson, T. (2015). A fast and scalable kymograph alignment algorithm for nanochannel-based optical DNA mappings. PloS One. doi:10.1371/journal.pone.0121905.

    Google Scholar 

  14. Thayanithy, V., Dickson, E. L., Steer, C., Subramanian, S., & Lou, E. (2014). Tumor-stromal cross talk: direct cell-to-cell transfer of oncogenic microRNAs via tunneling nanotubes. Translational Research, 164, 359–365.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Han, H., Hu, J., Yan, Q., Zhu, J., Zhu, Z., Chen, Y., Sun, J., & Zhang, R. (2016). Bone marrow derived mesenchymal stem cells rescue injured H9c2 cells via transferring intact mitochondria through tunneling nanotubes in an in vitro simulated ischemia/reperfusion model. Molecular Medicine Reports, 13, 1517–1524.

    CAS  PubMed  Google Scholar 

  16. Jackson, M., Morrison, T., Doherty, D., Mc Auley, D., Matthay, M., Kissenpfennig, A., O’Kane, C., & Krasnodembskaya, A. (2016). Mitochondrial transfer via tunneling nanotubes is an important mechanism by which mesenchymal stem cells enhance macrophage phagocytosis in the in vitro and in vivo models of ARDS. Stem Cells, 34, 2210–2223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wang, H., Hung, S., Peng, S., Huang, C., Wei, H.-M., Guo, Y.-J., et al. (2004). Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord. Stem Cells, 22, 1330–1337.

    Article  PubMed  Google Scholar 

  18. Zani, B., & Edelman, E. (2010). Cellular bridges. Routes for intercellular communication and cell migration. Communicative & Integrative Biology, 3, 215–220.

    Article  Google Scholar 

  19. Veranic, P., Lokar, M., Schütz, G., Weghuber, J., Wieser, S., Hägerstrand, H., et al. (2008). Different types of cell-to-cell connections mediated by nanotubular structures. Biophysical Journal, 95, 4416–4425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. He, K., Shi, X., Zhang, X., Dang, S., Ma, X., Liu, F., et al. (2011). Long-distance intercellular connectivity between cardiomyocytes and cardiofibroblasts mediated by membrane nanotubes. Cardiovascular Research, 92, 39–47.

    Article  CAS  PubMed  Google Scholar 

  21. Plotnikov, E., Khryapenkova, T., Vasileva, A., Marey, M., Galkina, S., Isaev, N., et al. (2008). Cell-to-cell cross-talk between mesenchymal stem cells and cardiomyocytes in co-culture. Journal of Cellular and Molecular Medicine, 12, 1622–1631.

    Article  CAS  PubMed  Google Scholar 

  22. Watson, N., Divers, R., Kedar, R., Mehindru, A., Mehindru, A., Borlongan, M. C., & Borlongan, C. V. (2015). Discarded Wharton’s jelly of the human umbilical cord: a viable source for mesenchymal stem cells. Cytotherapy, 17, 18–24.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Lic. Lidia M. Lopez for her expert technical assistance with electron microscopy studies; Dr. Ines Rebagliata for her technical support in cell cultures and Dr. Cecilia Poderoso for kindly providing the pSUPER-retro plasmid.

Grant Support

UBACYT 20020130100258BA (to A. Brusco) and PICT 2010–2430 (to J.J. Poderoso).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alicia Brusco.

Ethics declarations

Disclosures

The authors indicate no potential conflicts of interest.

Electronic supplementary material

ESM 1

(PDF 4025 kb)

ESM 2

(MP4 7872 kb)

ESM 3

(MP4 3069 kb)

ESM 4

(MP4 5250 kb)

ESM 5

(DOC 21 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sanchez, V., Villalba, N., Fiore, L. et al. Characterization of Tunneling Nanotubes in Wharton’s jelly Mesenchymal Stem Cells. An Intercellular Exchange of Components between Neighboring Cells. Stem Cell Rev and Rep 13, 491–498 (2017). https://doi.org/10.1007/s12015-017-9730-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-017-9730-8

Keywords

Navigation