As regenerative medicine moves closer to the clinic, scientists are seizing opportunities for continual improvement. How can we avoid unwanted immune responses to cell therapies? What is the best way to manufacture billions of healthy cells to replace lost or diseased tissues? And how can we protect those cells on the perilous journey from the syringe to their destination inside the human body?
Last year, a University of Washington research team led by Cole DeForest, PhD, an Associate Professor of Chemical Engineering and Bioengineering, as well as a faculty member in the Institute for Stem Cell and Regenerative Medicine (ISCRM), unveiled a strategy to address some of these challenges: a novel recombinant protein-based hydrogel that dramatically improves the survival and engraftment of cells delivered via injection.
This biomaterial—formed from a single, genetically engineered protein—acts like ketchup: it liquefies under the pressure of injection and re-solidifies at the target site, shielding the cells from damaging mechanical forces and providing a supportive scaffold. Built around an intrinsically disordered protein called XTEN, the gel avoids immune reactions, offers consistent batch-to-batch reproducibility, and shows promise across multiple cell types—including heart, liver, and kidney cells—offering a more reliable path toward effective cell therapies.
After unveiling that technology, Dr. DeForest and his lab asked a new question. How can we achieve greater control over the cells once they have been injected? Like a travel agent who makes sure you arrive at your destination safely and shows you the sights once you get there.
The upgrade, detailed in the journal Science Advances, comes in the form of light-based technology, known as PhoCoil, that allows scientists to photodegrade the hydrogels that encase the cells. DeForest is the senior author of the paper. Nicole Gregorio, a former PhD student in the DeForest Research Group, is the first author. ISCRM faculty member Kelly Stevens, PhD, is also an author of the study.
PhoCoil offers the same features as the previous version of the gel, says DeForest. “It is still a single-component recombinant protein. It is still shear-thinning. And it is still biocompatible. The new innovation relies on incorporation of a genetically-engineered fluorescent protein that falls apart when it’s hit with light, even through the skin. The upshot is you get the benefit of cell protection throughout injection alongside the newfound ability to free the cells on demand for them to move them around and better populate the host tissue.”
How could PhoCoil be useful in the clinic someday?
As regenerative medicine, doctors might inject batches of cells for a number of reasons. To promote faster and more effective healing of a joint. Or as medicine or antibiotics to fight a disease or virus. Either way, after administering an infusion of cells, a physician could shine a light that penetrates through the skin to control the location, timing, or dosage of the intervention.
In the investigation, the Stevens Lab showed that mice-implanted gels could be broken down with light. Across town, Dr. Jim Olson, whose lab at Seattle Children’s Hospital studies childhood cancer, demonstrated that the gels and their needle-based administration do not induce an immune response.
Looking ahead, DeForest is eager to pursue more possible applications of the PhoCoil gel. He and ISCRM colleague Dr. Yuzuru Sasamoto are exploring whether it could be used to treat limbal stem cell deficiency. And, he envisions collaborating further with Dr. Stevens on her efforts to regenerate the liver. “The tool is pretty well defined and well characterized now,” says DeForest.” The great part of being in ISCRM is that we can team up with many other investigators and hopefully put these platforms to good use.”