Direct Observation of Tunneling Nanotubes within Human Mesenchymal Stem Cell Spheroids
Tunneling nanotubes (TNTs) play an important role in cell-cell communication. TNTs have been predominantly reported among cells in monolayer culture. Using various imaging modalities, including scanning electron microscopy (SEM) and laser scanning confocal microscopy (LSCM), this work reports the finding of TNTs between cells within human mesenchymal stem cell (MSC) spheroids. TNTs visualized by SEM are consistent in size and geometry with those observed in cellular monolayer culture. LSCM imaging of living spheroids confirms the presence of F-actin filaments within the TNTs, which are known to maintain nanotube integrity. In addition, LSCM revealed the distribution of F-actin fibers across the entire spheroid body instead of being confined within individual cells. Intracellular material transport by TNTs was tested in MSC spheroids treated with cytochalasin D (CytoD), a known actin polymerization inhibitor for disrupting TNT formation. CytoD treatment decreased the transport of cytosolic material by at least four-fold compared to untreated spheroids. To the best of our knowledge, this work represents the first direct observation of TNTs within MSC spheroids. These findings offer new physical insight into cellular interactions within spheroids, providing structural information for increasing interests in spheroid-based cell therapy.
J. Zhang et al., "Direct Observation of Tunneling Nanotubes within Human Mesenchymal Stem Cell Spheroids," Journal of Physical Chemistry B, vol. 122, no. 43, pp. 9920-9926, American Chemical Society (ACS), Nov 2018.
The definitive version is available at https://doi.org/10.1021/acs.jpcb.8b07305
Electrical and Computer Engineering
Keywords and Phrases
Cell culture; Cell signaling; Monolayers; Nanotubes; Proteins; Scanning electron microscopy; Yarn, Actin polymerization; Cell-cell communications; Cellular interaction; Direct observations; Human mesenchymal stem cells; Intracellular materials; Laser scanning confocal microscopy; Structural information, Stem cells
International Standard Serial Number (ISSN)
Article - Journal
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