The healing of wounded skin in diabetes can be sped up by more than 50 percent using injections of stem cells taken from bone marrow, a new study in mice shows.
The research, led by scientists at NYU School of Medicine, focused on a chain of events in diabetes that makes skin sores more likely to form and less likely to heal.
Namely, the body’s failure in diabetes to break down dietary sugar creates molecules called free radicals that can wreak havoc on cells and damage their DNA. These free radicals also trigger an inrush of immune cells and chemicals meant to fight infection that, researchers say, instead kill normal cells and cause diabetic skin ulcers. These wounds, they note, can take twice as long to heal as in healthy mammals and are prone to infection.
Published in the January issue of the journal Diabetes, the study showed that the injected stem cells restore a cell signaling pathway called Nrf2/Keap1, recently shown by the NYU Langone team to be disrupted in diabetes. The rebalancing brought on by stem cell therapy, the researchers say, decreased wound healing time to 21 days in treated diabetic mice compared with 32 days in untreated diabetic mice. By contrast, normal mouse skin wounds usually heal in 14 days.
“Our study shows that in mice, stem cell–based therapies can stimulate the Nrf2/Keap1 pathway to counteract inflammation and restore some of the skin’s tissue-regenerating abilities impaired by diabetes,” says senior study investigator and plastic surgeon Daniel J. Ceradini, MD, an assistant professor in the Hansjörg Wyss Department of Plastic Surgery at NYU Langone Health.
The early-stage stem cells used in the current study are the kind that have the potential to mature into more than one kind of cell, but then specialize to serve within a particular mammalian organ like the skin. While essential to the formation of the body in the womb, pools of stem cells also persist in the adult body, where they can be triggered to serve as replacement parts when tissues are damaged, the goal of regenerative medicine.
Previous research by the NYU Langone team had shown that in human diabetes, stem cells do not contribute normally to tissue regeneration. This led the team to test what injections of donated stem cells, known to deter an immune response, might do to correct the dysfunction.
Dr. Ceradini, director of research in plastic surgery at NYU Langone, says that if future experiments prove successful, his team’s stem cell therapy could help in the healing not just of diabetic skin ulcers but also in repairing damage to diabetes-inflamed blood vessels.
The Centers for Disease Control and Prevention’s latest figures show that more than 30 million Americans have diabetes, for which researchers estimate that 1 in 10 will develop some form of diabetic skin wound, typically a foot ulcer. Although rare, some of these can result in the need for amputation. Researchers have estimated the annual healthcare costs in the United States from skin wounds related to diabetes at more than $9 billion.
Study first author Piul S. Rabbani, PhD, says “other than keeping wounds moist and covered,” there are few treatment options for diabetic skin ulcers. She cautions that, although several labs have reduced the inflammation behind skin ulcers in early experiments, clinical trials using stem cells are still several years away. Dr. Rabbani, a research assistant professor at NYU Langone, says the research team next plans to develop an experimental stem cell–based therapy for testing in larger mammals.
Funding support for the study was provided by the American Diabetes Association Pathway Stop Diabetes Accelerator Award 1-16-ACE-08; National Institutes of Health grants P30 CA016087, S10 OD010584, and S10 OD018338; and New York State Stem Cell Science grant C026719.
Besides Drs. Ceradini and Rabbani, other researchers involved in these experiments, performed entirely at NYU Langone, are Marc Soares, MD; Sophia Hameedi, BA; Rohini Kadle, MD; Adnan Mubasher, MD; and Maria Kowzun, MD.