Stem cells…now showing in 3D

Growing organs in vitro is one of the ultimate dreams of any stem cell biologist. As such, it seems obvious that some of these organs will need to be grown in 3D. This is why stem cell 3D culture systems are very fashionable among scientists. They are increasingly successful and a fair amount of exciting scientific publications have blossomed in the recent years.

One of these was recently published in Stem Cell Reports by Meinhardt and colleagues. They show that individual embryonic stem cells (stem cells that can become any type of cell in the body), when embedded in a 3D matrix and grown with a medium that induces neural differentiation, can form structures (called neuroepithelial cysts) that mimic early neural development.

In this picture, you can observe mouse embryonic stem cells cultured in the 3D matrix (called Matrigel) for 2 days (left picture), 4 days (middle picture) and 7 days (right picture). Up until day 4 of culture, you can observe a fairly simple “flower” structure with the protein E-cadherin in white and cell nuclei containing DNA in blue. After 7 days in culture, you can observe a more organized structure with a lumen (inside space of a tubular structure) with the proteins Sox1 in green and N-cadherin in red, which are typical markers of ‘neuroepithelial’ cells. Also, the expression of N-cadherin is polarized. From these observations, the authors conclude that in their culture conditions, mouse embryonic stem cells grow into an organized structure of more specialized ‘neuroepithelial’ cells.

Further experiments presented in this study show that both the timing and the developmental steps that are observed during the differentiation of mouse embryonic stem cells into these neuroepithelial cysts are similar to those observed during mouse development. Additionally, they show that upon stimulation with various “morphogenetic” factors (substances governing tissue development and the positions of the various specialized cell types within a tissue) they can obtain structures resembling a patterned neural tube with a dorso/ventral axis.

This study nicely illustrates how 3D stem cell culture systems are an invaluable tool to study the action morphogenetic factors during the development of organs Also, these “mini organs” could also constitute a source of tissues (in this case, the neural tube), which hopefully, one day in the near future, will find their way into real 3D stem cell therapies!

Picture credit:

Meinhardt, A., Eberle, D., Tazaki, A., Ranga, A., Niesche, M., Wilsch-Bräuninger, M., Stec, A., Schackert, G., Lutolf, M., & Tanaka, E. (2014). 3D Reconstitution of the Patterned Neural Tube from Embryonic Stem Cells Stem Cell Reports, 3 (6), 987-999 DOI: 10.1016/j.stemcr.2014.09.020

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