Principal Investigator: Luis Garza, MD, PhD
Performing Organization: Johns Hopkins University
Background: Stem cell therapy holds great promise in medicine. This grant will employ one’s own stem cells in an attempt to help the more than 1.7 million (1 out of every 200) people in the US who have had limb amputations—including military (see below). While improvements in prosthetics are clear, their use is still dramatically limited by discomfort, pain and skin-breakdown at the stump site. In the same way we wear shoes every day without problems, our long-term goal is to aid prosthetic use by permanently converting the skin at the stump site to volar type (palmo-plantar) skin. Volar skin has many adaptations that allow it to be pressure and friction resistant. We believe our cellular therapy can enhance these features at the stump site of amputees to make their prosthetic use easier and without self-induced limitations on activity.
But more than this, we hope this grant can be a spring-board for the use of cellular therapy as a new generation of medicines for the wounded warrior. Currently medicine is dominated with pills and surgery, but a new third arm of medicine will be cell therapy. They can be tailored to treat a wide variety of diseases of the wounded warrior. We hope this therapy can be a platform to establish workflows to send cells for therapy to military physicians at military treatment facilities to start a pipeline of developing novel cellular therapies for the wounded warrior. Our phase 1 results were recently published in Science Magazine (https://www.science.org/doi/10.1126/science.adi1650).
Military Relevance: With improvements in body armor, amputation rates have been increasing. Tremendous advances exist in prosthetic design. However, even in the best conditions these prosthetics are not used as frequently and easily as shoes, for example. Reprogramming volar skin at the stump site will move towards the goal of an amputee wearing a prosthetic most waking hours without discomfort. These issues are very real for the enlisted and veterans. In our study, 1/3 of Vietnam veterans reported stump problems for an average of at least 1 month in the last year—40 years after their initial injury. The permanent change of skin at the stump site holds the potential to radically enhance the lives of our wounded warriors.
Hypothesis/Objective: Just as we have shown in our normal human subject volunteers, autologous volar fibroblasts will have the ability to induce volar features at the stump site of wounded warriors and civilian amputees.
Specific Aims: Conduct a Phase 2 clinical trial in amputees to test for increased epithelial thickness and improvements in quality of life.
Study Design: We propose a multi-site trial including Hopkins, Brooke Army Medical Center, Naval Medical Center San Diego and Walter Reed. We will enroll below the knee amputees from trauma, biopsy a palm or sole, expand volar fibroblast stem cells, and then inject into the stump site. We will monitor the injected area noninvasively, and compare baseline to post-treatment surveys to determine improvements in quality of life.
Types of Patients this will help and how: We expect this to help all amputees, but particularly those with discomfort at their stump site by making the skin pressure adaptive at the stump site.
Potential clinical applications and benefits and risks: Prosthetic abandonment is common among especially long-standing amputees. Making the skin at the stump skin like palmo-plantar skin should dramatically improve the use of prosthetics. The risks were very low in our phase 1 trial and included initial reactions like local bruising or swelling that was temporary.
Timeline for results; Future outcomes
After cell injection, we can detect increases of skin firmness within several days. In future iterations of this therapy, we hope to modify the genes of injected cells to make them more potent to regenerate tissue in wounded warriors.