Using Light to Optically Regulate Cell Fate for Regenerative Medicine

Researchers at Istituto Italiano di Tecnologia (IIT) have shown that optical modulation can be exploited to directly control the fate of a progenitor cell population to facilitate the formation of new blood vessels. The researchers combined the use of photosensitive, biocompatible polymers with visible light excitation to gain optical control of cell fate.

The team focused on endothelial progenitor cells (EPCs) and, in particular, on endothelial colony-forming cells (ECFCs). ECFCs were mobilized from a bone marrow and vascular stem cell niche to reconstruct the vascular network destroyed by an ischemic insult and to restore local blood perfusion. The in vitro activation of ECFC angiogenic activity was made possible by the use of a conjugated polymer as the phototransduction element. The researchers demonstrated that polymer-mediated optical excitation could enhance lumen formation in vitro. They identified the underlying biophysical pathway as being due to light-induced activation of a Ca²⁺-permeable transient receptor potential vanilloid 1 (TRPV1) channel.

Using light to manipulate the signaling pathways that drive ECFC proliferation, migration, differentiation, and tubule formation could represent a reliable strategy to improve the regenerative outcome of therapeutic development of new blood vessels in the harsh microenvironment of an ischemic tissue, such as an infarcted heart.

A new study shows that it is possible to precisely control the fate of tissue cells by using visible light.

The researchers said that the results represent, to the best of their knowledge, the first report on the use of polymer photoexcitation for the in vitro modulation of ECFC fate and function. Overall, they believe the findings represent the proof of principle that optical modulation can be successfully exploited to directly control the fate of a progenitor cell population, which has been shown to support revascularization of ischemic tissues.

“We are talking about a completely new technique that could lead us to important outcomes in tissue engineering. The use of light as a stimulus is much more versatile and much less invasive compared to the use of electrodes; it can be directed in a more specific way on different cell populations,” researcher Maria Rosa Antognazza said.

The next step for the researchers will be to broaden the potential of their technique by using other cell models of interest for tissue regeneration. The possibility of modulating the cell fate by optical stimulation allows researchers to be highly precise and minimally invasive; therefore, it could be suitable for several applications in the therapeutic field.

The research was published in Science Advances (https://doi.org/10.1126/sciadv.aav4620).