An illustration of an iPSC colony emerging in a three-dimensional gel made with DEMCON Nymus3D. [Matthias Lutolf, EPFL]
An illustration of an iPSC colony emerging in a three-dimensional gel made with DEMCON Nymus3D. [Matthias Lutolf, EPFL]

A convergence of physical and chemical factors can turn adult cells into stem cells more efficiently than chemical factors alone. The physical factors that can help induce pluripotency amount to a kind of cellular swaddling, the formation of a three-dimensional embrace that can be loosened or tightened as needed.

That adult cells might need cuddling should come as no surprise, even though cell cultures are typically two dimensional. Cells in the body exist in a three-dimensional world.

To explore the possibilities of three-dimensional cultures, scientists based at Ecole Polytechnique Fédérale de Lausanne have been engineering three-dimensional extracellular matrices—gels, in short. These scientists, led by Matthias Lutolf, Ph.D., report that they have developed a gel that boosts the ability of normal cells to revert into stem cells by simply “squeezing” them.

The details of the scientists' work appeared January 11 in the journal Nature Materials, in an article entitled, “Defined three-dimensional microenvironments boost induction of pluripotency.” The article describes how the scientists modulated microenvironmental stiffness, degradability, and biochemical composition to identify a previously unknown role for “biophysical effectors” in the generation of induced pluripotent stem cells (iPSCs).

“We find that the physical cell confinement imposed by the 3D microenvironment boosts reprogramming through an accelerated mesenchymal-to-epithelial transition and increased epigenetic remodeling,” wrote the authors. “We conclude that 3D microenvironmental signals act synergistically with reprogramming transcription factors to increase somatic plasticity.”

Essentially, the researchers discovered that they could reprogram the cells faster and more efficiently than current methods by simply adjusting the composition—and hence the stiffness and density—of the surrounding gel. As a result, the gel exerts different forces on the cells, “squeezing” them.

As a new phenomenon, this is not entirely understood. However, the scientists propose that the three-dimensional environment is key to this process, generating mechanical signals that work together with genetic factors to make the cell easier to transform into a stem cell.

“Each cell type may have a 'sweet spot' of physical and chemical factors that offer the most efficient transformation,” said Dr. Lutolf. “Once you find it, it is a matter of resources and time to create stem cells on a larger scale.”

Possiby the greater achievement of this discovery is quantity. The technique can be applied to a large number of cells to produce stem cells on an industrial scale. Dr. Lutolf's lab is looking into this, but their main focus is to better understand the phenomenon, and to find the “sweet spots” for other cell types.








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