A Massachusetts General Hospital (MGH) research team has found a surprising potential solution to a persistent clinical problem — the healing of chronic wounds. In their report published in Wound Repair and Regeneration, the investigators from the MGH Vaccine and Immunotherapy Center (VIC) describe how application of mature B lymphocytes — the immune cells best known for producing antibodies — greatly accelerated the healing of acute and chronic wounds in both diabetic and nondiabetic mice. The treatment also improved the quality of regenerated tissue and reduced scarring.
Patients with diabetes are at risk of developing chronic wounds, particularly foot ulcers, because of two complications of the illness. Neuropathy damages the nerves in the skin, particularly the hands and feet, causing a loss of sensation that can lead to repeat injuries of the same structures. Vascular disease limits blood flow to the skin and adjacent tissues, cutting off the supply of oxygen and nutrients required for healthy tissue healing. Between 19 and 34 percent of patients with diabetes develop chronic foot ulcers, the presence of which significantly increases their risk of death compared with patients without foot ulcers.
Healthy wound healing has four phases: blood clotting to stop bleeding, inflammation to remove dead and damaged cells, proliferation of new tissue and the remodeling of tissues to be stronger and better organized. It is believed that chronic wounds get stuck in an inflammatory phase, with a low-oxygen microenvironment and the persistent presence of enzymes that break down tissue proteins. Recent studies from the VIC and other centers have identified several unsuspected roles for B lymphocytes, including the secretion of powerful anti-inflammatory molecules. A previous study from the MGH team found that injecting B cells into cardiac tissue damaged by a heart attack improved structural and functional recovery in an animal model.
Remarkably, the same healing effect was produced when B cells from older obese diabetic mice were applied to acute wounds in similarly aged, obese diabetic mice. Both groups of animals were equivalent to 55- to 60-year-old morbidly obese patients with uncontrolled diabetes, the most difficult population to treat. The sort of mature B cells used in this study have a limited life span, and once applied on a wound, they remained active at the site for up to 14 days. This makes them easier to control than other types of cells used in therapies and makes side effects unlikely. Overall, the presence of B lymphocytes was associated with increased tissue proliferation, reduced cell death and a more supportive environment for wound healing.
Mark Poznansky, MD, PhD, director of the MGH-VIC and senior author of the Wound Repair and Regeneration report adds, “Having a novel therapeutic that is based on the immediate isolation of a patient’s own cells, with minimal manipulation, will represent an attractive option for the wound care field; and a successful option that accelerates healing would greatly benefit patients, as diabetic ulcers typically need up to a year or more heal. Further development of the B cell application therapy may lead to novel ways of addressing the pathologies underlying the formation of chronic wounds.”
