Nanosensors detect health of transplant cells

After the successful publication of his most research findings, associate professor of radiology at the Hopkins School of Medicine Mike McMahon, advises undergraduates based on his own personal experiences.

“For undergraduates, one of the biggest things you have to learn is to accept that there are going to be a lot of failures for a pretty long period of time. You just have to be patient. It is a long build up.”

After years of investigation, failed attempts and numerous experiments, McMahon along with Jeff Bulte, director of Cellular Imaging at Hopkins’ Institute for Cell Engineering, have successfully collaborated and devised a method to determine the viability of cells that have been transplanted into living organisms. The new technology that their team has developed has the ability to determine if transplanted cells are alive or dead through the use of imaging techniques, including Magnetic Resonance Imaging (MRI).

This highly advanced technology involves the use of a nanosensor that contains a pH sensitive agent, L-arginine. This pH-sensitive agent responds to the transplanted cell death by causing a change in MRI contrast, thereby indicating cell death. Furthermore, the change in pH triggers the contrast agent, which is the main visual indicator of the transplanted cell condition. Depending on whether or not the cell is alive, the contrast can be viewed effectively with the use of MRI.

Kannie Chan, a research fellow of their team, started investigating whether or not this nanosensor would be useful for monitoring cell therapy about three years ago. To simulate the practical function of the nanosensors, they were placed into hydrogel spheres.

“We originally made these nanoparticles as imaging agents to monitor lymphatics system, and published a paper last year on that,” McMahon said. “We realized that they had very nice pH sensitivity.”

By incorporating these nanosensors in the hydrogel, their exchange with water is changed as a function of pH, which will indicate cell death.

“In principle, this universal modification of hydrogels can be applied for imaging of many cell types,” Chan said. Liver cells were used with hopes that this technology can be of benefit in the future to patients who suffer from liver failure.

“We used bioluminescence imaging to counter validate the cell viability, which is a standard for viability sensing in small animals,” Chan said.

Liver cells were used that can emit bioluminescent light when they are alive. Results indicate success in this technology, as the nanosensors and pH-detecting agent displayed the condition of the cells on the MRI that corresponded to the bioluminescence imaging. The light sensor cannot be used in humans because of the large size of human tissue and potentially harmful effects.

“The light can only go a couple of centimeters, so you would not see it in patients,” Bulte said. Eventually, the goal of this new technology is to move to larger animal models.”

For the medical community, there are high hopes that this technique will successfully work in humans. Specifically, such technology can be used as an aid in cell therapies for patients with chronic conditions such as Type I diabetes and liver failure. The amount of success in the cell therapy for such patients with these conditions heavily relies on the condition of the transplanted cells. The cell therapy would prevent doctors from having to remove infected organs from the body.

“This is a new technology which was developed for monitoring cell therapy, and we think it is showing great promise right now in the pre-clinical stage,” McMahon said. “We are planning to test it on a clinical scanner.”