Researchers have discovered a mechanism that causes wounds in people with diabetes to heal more slowly, increasing the risk of infection and other serious complications. They say their findings could provide a new way to treat the disease. Exosomes are nanoscale messenger particles naturally produced by cells and are responsible for communication between cells. They deliver "cargo" including proteins, lipids and genetic material to the receiving cell, effectively altering the cell's biological response.
Exosomes are associated with the body’s immune and inflammatory responses. Now, a new study led by researchers at the University of Pittsburgh examines the role of exosomes in people with diabetes, whose wounds tend to heal more slowly and progress more quickly, increasing the risk of infection and other serious complications.
"Wound healing in patients with diabetes is compromised by excessive inflammation. If left untreated, these non-healing or chronic wounds can lead to amputation," said Chandan Sen, one of the study's corresponding authors. "There are more than 100,000 diabetes-related amputations in the United States each year, but by further understanding wound healing and developing new treatments, our goal is to reduce this number."
The researchers collected fluid from negative pressure bandages on chronic wounds in 22 people with diabetes and 15 people without diabetes. Negative pressure wound therapy (NPWT) promotes wound closure by applying sub-atmospheric pressure to draw out fluid and infection. A special bandage is sealed over the wound and connected to a gentle vacuum pump.
"These bandages are usually thrown into the trash, but the wound fluid is actually a very valuable sample that reflects the condition of the entire wound. For example, if the wound is infected, the fluid will contain traces of infection," Mori said.
The researchers analyzed the fluid and isolated exosomes produced by keratinocytes, cells necessary for skin repair. Normally, when cargo-carrying exosomes are released from cells, they are taken up by macrophages, the immune cells that orchestrate wound healing.
They found that exosomes in diabetic patients - which they called "di-exosomes" - not only carried different cargo, but the number of di-exosomes in the wound fluid of diabetic patients was much lower than the number of exosomes in the wound fluid of non-diabetics, and the number of exosomes taken up by macrophages was also far lower than that of di-exosomes.
When macrophages from non-diabetic patients were incubated with exosomes, they produced factors that neutralized inflammation, suggesting that they were receiving the correct "wound healing" signals from the exosomes. However, when the experiments were repeated using heavy exosomes, the macrophages instead produced pro-inflammatory factors.
"If the signals in the exosomes are correct, the macrophages know how to address inflammation in the wound," Sen said. "In diabetic patients, the tandem between keratinocytes and macrophages is affected, so the macrophages keep driving inflammation and the wound fails to heal."
The researchers say their findings provide important insights into a major complication of diabetes and may provide a new way to treat diabetes.
"Exosomes can cause deviations in the wound healing cascade, thereby affecting the resolution of inflammation," Sen said. "And this is not limited to wounds. Since exosomes perform multiple functions in the body, heavy exosomes may play a role in other diabetes complications. This study opens up a new way of thinking."
Researchers are currently studying how to target exosomes to improve wound healing in diabetic patients. One approach, the researchers say, is to eliminate the chemical modifications that occur in gravitational spinners. Another approach is to isolate exosomes from diabetic patients, load them with the missing cargo, and then inject them into wound tissue.
The research was published in the journal NanoToday.