Stem cells hold enormous potential for repairing or regenerating damaged tissue. But delivery of these cells to their target location remains a major obstacle. Now, researchers at the Stanford University School of Medicine in California have developed a novel nanoparticle-based system that allows stem cells to be tracked in real time in a living mouse for up to a year after injection. This work, if replicated in humans, could finally allow scientists to verify if these cells are going where they’re intended.
“Delivering stem cells to specific tissues is a very big challenge, since basically all investigators have to shoot blindly,” says Sanjiv Gambhir, director of Stanford’s molecular imaging program who led the work published online today in Science Translational Medicine. “For these cell therapies to succeed, you need imaging systems.”
Gambhir and his team started with a type of nanoparticle already used in clinical trials to guide cancer drug delivery. They then attached two imaging agents to the nanoparticle: gadolinium, a contrast agent picked up by magnetic resonance imaging (MRI), and a fluorescent compound called fluorescein. Although the resulting composite nanoparticle was less than a micron in diameter, it aggregated once absorbed by a cell, making it large enough be imaged by ultrasound and MRI.
After injecting bone marrow stem cells labeled with these particles into the hearts of healthy mice, the researchers found that they could track the cells using a standard ultrasound device. The MRI contrasting agent allowed the team to monitor long term survival or deposition patterns of labeled stem cells without harming the animals. And when necessary, the fluorescent tag allowed for accurate post-mortem examinations as well. Nanoparticle imaging also demonstrated remarkable sensitivity, as the researchers were able to visualize as few as 75,000 stem cells with ultrasound, and a few hundred thousand with MRI.
Although the materials utilized in the study have already been used in clinical trials, Gambhir acknowledges that this new composite nanoparticle requires strenuous safety testing before it could be ready for human use. Still, he was encouraged by the finding that the nanoparticles did not affect stem cell differentiation or division.
The researchers first plan to test the system in larger animal studies with other populations of stem cells. Ghambir believes it could be ready for human testing within the next five years. “This enables cell therapy to understand why it’s failing. This allows you to connect the dots,” he says.
Check out the video of labeled stem cells being injected into a mouse heart below (stem cells circled in red):