Putting Stem Cells In Their Place

People with chronic diseases like diabetes and multiple sclerosis have inflamed, leaky blood vessels, heightening their risk of heart attack and stroke. Some scientists envision using a patient’s own stem cells to regrow healthy tissue to plug the leaks and calm inflammation. A new polymer coating could help these stem cells find and adhere to inflamed endothelial tissue (J. Am. Chem. Soc., DOI: 10.1021/ja400636d).

Targeting stem cells to specific tissues, such as the inner walls of inflamed blood vessels, is tricky because once injected into a person’s bloodstream, the cells quickly spread throughout the body. Some researchers have tried to chemically modify the membranes of stem cells to make them stick to certain tissues. However, these complex chemical treatments are laborious and can kill the cells, says Hyunjoon Kong of the University of Illinois, Urbana-Champaign. “We wanted to find a molecule that would self-assemble into the stem cell membrane and guide the cell to the target tissue,” he says. “Then, a doctor could simply mix a patient’s own stem cells with our molecule and inject the mixture.”

Kong and his coworkers synthesized a targeting molecule containing vasculature binding peptides, which bind to a protein that is abundant on the surfaces of inflamed blood vessels. The scientists attached these peptides to branched polyglycerol polymers that acted as a scaffold to display the homing peptides. To link the peptides to the cell, they added greasy octadecyl hydrocarbon chains to the polymers. These chains spontaneously embed into stem cells’ lipid membranes.

To test the molecule’s homing abilities, the scientists injected mesenchymal stem cells that they had mixed with the targeting molecule into a microfluidic device that mimicked a blood vessel. The device pumped cells over a sheet of endothelial cells that acts like inflamed tissue. The researchers counted how many stem cells adhered to the sheet. Compared with unmodified stem cells, twice as many stem cells coated with targeting molecules stuck to the cell sheet.

Kong thinks the team can improve the affinity of the targeting molecule for the inflamed tissue by tweaking the branched polyglycerol’s structure so that the peptide and hydrocarbon chain don’t bump into each other.

Elliot Chaikof, a stem cell biologist at Harvard Medical School, calls the study an “elegant approach” for targeting stem cells to sites of inflammation. However, he says, the real test of the molecules’ effectiveness will be animal studies.

The researchers are now testing the ability of the polymer-coated stem cells to repair ruptured blood vessels in mice, and Kong says preliminary results are encouraging.