Targeted delivery of therapeutics remains one of the thorny issues in medical development. Everyone wants a way to deliver high doses of a therapeutic to a specific location in the body without it also ending up everywhere else. The major issue is that systemic administration will send the majority of whatever is injected into the body into the liver and lungs, and that limits the dose that can be applied to any other tissue. One approach is to conduct localized injections, but these remain a good option for internal organs only in cases of serious damage. For example, researchers here report on the adaptation of keyhole surgery techniques to the delivery of exosomes to the injured heart following a heart attack, in order to spur greater regeneration.
Scientists have explored using stem cell therapy as a way to regrow tissue after a heart attack. But introducing stem cells directly to the heart can be risky because they could trigger an immune response or grow uncontrollably, resulting in a tumor. Therefore, researchers have tried injecting exosomes – membrane-bound sacs containing proteins, lipids, and nucleic acids secreted by stem cells – into the heart, but they often break down before they can have therapeutic effects. Others have developed cardiac patches, or scaffolds that help implanted exosomes last longer, but they usually must be placed on the heart during open-chest surgery. Researchers wanted to develop an exosome solution that could be sprayed onto the heart through a tiny incision, avoiding major surgery.
The researchers mixed exosomes from mesenchymal stem cells with fibrinogen, a protein involved in blood clotting. They added this solution to a tiny, double-barreled syringe that contained a separate solution of another clotting protein called thrombin. When the team sprayed the solutions out of the syringe onto a rat’s heart through a small chest incision, the liquids mixed and formed an exosome-containing gel that stuck to the heart. A mini-endoscope, inserted through a second small incision, guided the spray needle. In rats that had recently had a heart attack, the exosome spray lasted longer, healed injuries better and boosted the expression of beneficial proteins more than heart-injected exosomes. In pigs, the spray caused less severe immune reactions and surgical stress than open-chest surgery. The spray is a promising strategy to deliver therapeutic exosomes for heart repair.