A UM Miller School trauma surgeon who cares for burn patients, and a UM dermatologist who is already healing chronic wounds with stem cells, have been awarded $3 million from the U.S. Department of Defense to conduct the nation’s first clinical trial on the safety and efficacy of using donor mesenchymal stem cells to promote healing and reduce scarring in acute burn patients.
If proven successful, stem cell therapies could revolutionize burn care on the battlefield and the home front, reducing both the physical and emotional scars that millions of burn patients suffer, as well as the enormous cost of long-term reconstructive surgeries, and physical and psychological therapy.
“This is extremely exciting,’’ said Principal Investigator Carl Schulman, M.D., Ph.D., M.S.P.H, associate professor of surgery and Director of the William Lehman Injury Research Center. “This study has the potential to dramatically change the standard of care by offering a regenerative treatment before the burn scar process begins.”
“It really is groundbreaking,” added Co-Principal Investigator Evangelos Badiavas, M.D., Ph.D., associate professor of dermatology and cutaneous surgery and a member of the Interdisciplinary Stem Cell Institute (ISCI). “Today, many soldiers wounded in combat situations survive, but are often horribly burned. And who gets burned here? Kids. These are young people in the prime of their lives. The University and ISCI are becoming more aggressive about burn wounds because there is a real opportunity to do so much good.”
The defense grant, the second which Badiavas and Schulman have received this year, builds on Badiavas’ previous work demonstrating the safety of delivering autologous bone marrow cells, including mesenchymal stem cells, to chronic wounds. In an ongoing NIH- and ISCI-sponsored clinical trial, he also has shown dramatic improvement in healing and reducing, even preventing, scarring from chronic pressure sores, diabetic ulcers and other non-healing wounds, which affect nearly 6 million Americans.
“The chronic wound patients we’ve healed actually have little evidence of scarring and you would expect significant scarring with their wounds, which are horrible,” Badiavas said. “So we’re very excited about the prospects for acute burn patients who haven’t scarred yet. We have evidence from animal studies that shows we can reduce the inflammation that leads to scarring.”
To date, most stem cell research for burn wounds has focused on autologous stem cells harvested from the patient, but Schulman said the U.S. military is committed to finding allogeneic solutions because they would be readily available for rapid and large-scale application.
“For military purposes, and for a lot of civilian purposes, the advantage of having an off-the-shelf product you can apply to a burn wound is huge,” Schulman said. “Most of the other stem cell solutions are using — or are thinking about using — autologous stem cells, which means you have to acquire them at the time of burn injury, or shortly thereafter, and that would delay the process. Burn patients can’t wait.”
For their new trial, which will combine Phase 1 and 2 trials over four years, Schulman and Badiavas plan to enroll 100 patients admitted to the UM/JMH Burn Center with second-degree burns. The initial 20 participants will take part in the safety phase, receiving multiple and escalating doses of the stem cell product, which will be injected or applied topically to their burn wounds. Once safety is ensured, 80 patients will be randomized into two groups, half who, along with the standard of care, will receive up to four doses of allogeneic stem cells over a period of weeks to months, and half who will receive the standard of care.
“We’ve noted from prior trials that you need multiple doses to heal difficult wounds,” Badiavas said. “One is not going to do it, so this will be the first trial looking at multiple administrations of allogeneic mesenchymal stem cells.”
Badiavas is also the Principal Investigator and Schulman a collaborator on a $2.2 million pre-clinical trial recently funded over three years by the Department of Defense. Working in partnership with the Armed Forces Institute of Regenerative Medicine, they and Stephen C. Davis, research professor in the Department of Dermatology and Cutaneous Surgery, will explore treatments, including autologous and allogeneic stem cells and lasers, to reverse mature scars from severe third-degree burns.
“We are enourmously excited about these new applications of mesenchymal stem cells to skin disorders and injuries,” said Joshua M. Hare, M.D., Director of the Interdisciplinary Stem Cell Institute. “These new studies are broadly advancing UM’s efforts in regenerative medicine.”