Scientists have found a chemical procedure to anchor stem cells to blood vessel walls, which in turns gives them a higher change of reaching their target and exerting a therapeutic effect.
“Delivery remains one of the biggest hurdles to stem cell therapy,” explains senior author Jeffrey Karp, an instructor at the Harvard-MIT Division of Health Sciences and Technology. “The blood stream offers a natural delivery vehicle, but stem cells don't move through blood vessels normally after being expanded in culture.”
Cultured stem cells go with the blood flow, which means they seldom contact the sides of blood vessels and thus have fewer opportunities to escape into the surrounding tissue to rebuild damaged structures.
The research team started by refining a February study in which researchers at Brigham and Women’s Hospital used a method involving enzymes to have a molecule related to Sialyl Lewis x (SLeX) form temporary connections with proteins on blood vessel walls.
To eliminate the use of enzymes, which reportedly made the process complication, the current research used biotin, streptavidin, and SLeX. The new method took 45 minutes, and was able to maximize the ability of stem cells to roll along the interior of blood vessels, rather than getting lost in the flow, according to the scientists.
“The method is very simple,” according to Debanjan Sarkar, Ph.D., who is first author on the paper. “Plus, biotin and streptavidin work with many molecules, so labs can use this universal anchor we discovered to tackle other problems. They're not limited to sticking SLeX on cells.”
The team worked with human cells extracted from the bone marrow in cultures including mesenchymal stem cells (MSCs). When the investigators input the three molecules one after the other into cell culture, biotin and streptavidin anchored SLeX to the cell surface. The team then tweaked the concentrations of each molecule to maximize the cell's ability to move inside the blood vessel without getting lost. The researchers report that they also confirmed that the altered cells were still viable.
The study was done under a collaboration between Massachusetts Institute of Technology, Harvard Medical School, and Harvard University, and some local teaching hospitals and research centers. It is published online in Bioconjugate Chemistry on October 31.