Hijacking cellular ‘mail’ for regenerative medicine

Pilot research shows bone deficits treated with engineered exosomes (right) heal quicker when compared to deficits without exosome treatment (left). Photo: Sriram Ravindran and Praveen Gajendrareddy

University of Illinois at Chicago researchers have received approximately $2 million in funding from the National Institutes of Health to develop a better way to regenerate bone or tissues that have been lost to disease or injury.

Currently, most treatments rely on the use of growth factors or other chemical agents to stimulate stem cells, which have the ability to grow into any type of cell in the body, to regenerate what has been lost. But this approach has many limitations, like side effects and uncontrolled abnormal growths due to dosing and toxicity, which have caused complications and prevented regulatory organizations from approving the treatments for use in humans.

“We need a replacement for growth factor-based interventions so that we can reduce side effects and advance these therapies to the bedside,” said Sriram Ravindran, co-principal investigator of the project. “We need therapies that better mimic the body’s natural processes, so the body is better able to tolerate treatment.”

Bone is the second most transplanted organ in the human body, after blood. Grafting and regeneration procedures are performed by health care providers to treat anything from complex bullet wounds and spinal injuries to gum disease.

Ravindran, research assistant professor of oral biology, and his colleague, Praveen Gajendrareddy, jointly run a lab at the UIC College of Dentistry that develops biomimetic tools — those that mimic natural biology — for tissue regeneration. With this latest round of funding, they hope to evaluate and characterize the use of engineered exosomes — small vesicles in cells that carry cellular messages — as a safer and more clinically promising alternative to growth factors.

“Our preliminary research has demonstrated that engineered exosomes may aid regeneration faster than growth factors, with fewer complications,” said Gajendrareddy, co-principal investigator and associate professor of periodontics. He says that because exosomes are already used by the cell to carry messages, it makes sense to see if it is possible to amplify their function to predictably carry messages that stimulate stem cells.

Sriram Ravindran

Praveen Gajendrareddy

“Because these engineered exosomes mimic nature, we are not reinventing the wheel, we are just making the wheel go a bit faster, while better controlling the direction it travels,” Gajendrareddy said.

Ravindran and Gajendrareddy will use the new funding to further develop their exosomes to be, what they call, functionally activated targeted exosomes, or FATE, and will evaluate the exosomes’ effectiveness in healing critical-size skull defects in rodents.

“We want to create exosomes that behave predictably — we want to control their function within the extracellular matrix in stimulating stem cells into specific, target cell types,” Ravindran said. “I think we are close.”

“We hope to demonstrate promising bone regeneration with limited side effects, as a proof-of-concept,” Gajendrareddy said. “The end goal of this research is to develop new methods of treating bone and tissue loss that can help all kinds of injuries, in all kinds of settings.”

In addition to more obvious uses — like treating large skull fractures or bone loss due to gum disease — researchers said other examples of potential applications of exosome-based regenerative medicine include the portable use of such therapies by the military to delay tissue loss until injured soldiers are transported to a medical facility, as well as prolonging the viability of hip and knee replacements to better match longer life expectancies.

Collaborating with Ravindran and Gajendrareddy on this research are Chun-Chieh Huang, postdoctoral research associate, and Dr. Lyndon Cooper, associate dean for research at the college.