Characterization of Tunneling Nanotubes in Wharton’s jelly Mesenchymal Stem Cells. An Intercellular Exchange of Components between Neighboring Cells
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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.
KeywordsTunneling nanotubes Mesenchymal stem cells Mitochondrial transfer Intercellular communication Intercellular bridges
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.
UBACYT 20020130100258BA (to A. Brusco) and PICT 2010–2430 (to J.J. Poderoso).
Compliance with Ethical Standards
The authors indicate no potential conflicts of interest.
- 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.CrossRefGoogle 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.CrossRefPubMedPubMedCentralGoogle 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 CrossRefGoogle 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.PubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle Scholar