The palms of our hands and the bottoms of our feet aren’t the flashiest body parts, but they have a secret superpower that we don’t often appreciate—the ability to bear weight.
“There was this one moment where an aquatic vertebrate, like a fish, slapped its fin on the sand, and that started terrestrial evolution,” Luis Garza, M.D., Ph.D., a dermatologist at Johns Hopkins University, told Fierce Biotech in an interview. “We think when that fin hit the sand that started millions and millions of years of pressure adaptation.”
But for those with amputated limbs, skin that never evolved to sustain pressure is now being asked to do so—for example, the end of a residual leg limb outfitted with a prosthetic. Asking this thinner skin to bear weight can lead to wounding and discomfort, and a fear of developing these problems can lead amputees to limit the use of their prosthetics.
In a small human trial, Garza and colleagues have successfully transplanted skin cells from the soles of healthy volunteers’ feet into their thighs, transforming a small section of skin into a tougher form. By understanding this tougher type of skin and how to transplant it, the researchers hope to create a new cell therapy that can prevent residual limbs from being damaged by prosthetic use.
The results were published in Science on Sept. 6.
“The work explores both the basic science but also those important pre-clinical issues about manufacture, efficacy [and] safety, and then there is the proof of the pudding in the healthy volunteer trial,” John McGrath, M.D., a dermatologist at King’s College London who was not involved with the study, told Fierce Biotech in an email.
It’s easy to think of skin as one giant, continuous organ, but it comes in many different forms. Volar skin, on our palms and soles, has evolved to withstand regular high-impact contact. In 2002, researchers realized that skin cells called fibroblasts actually express genes differently depending on where in the body they come from—and if you take them from the body and grow them in a petri dish, they retain this genetic identity.
Deep in the dermis, these fibroblasts can then in turn influence the epidermis above them, the layer of skin that interacts with the world.
“Everyone used to think that the fibroblast is just a work-horse cell in the dermis, making collagens, healing wounds,” McGrath said. “The concept that these cells could also influence other skin cells to change behavior was a real eye opener.”
Garza and colleague Sam Lee, Ph.D., also of Johns Hopkins, first looked at volar fibroblasts in the lab. They saw that when grown in culture, volar fibroblasts were much more mobile than other fibroblasts and also moved in a characteristic “slingshot” motion with sudden bursts of activity. Applying pressure to the cells also increased the activity of unique genes that didn’t respond to pressure in other non-volar skin cells from the scalp.
When grown in a bio-printed “mini-skin,” volar fibroblasts induced epidermis cells to become thicker and more like the soles of feet. This success led Garza and Lee to move from the lab bench to the clinic.
In a phase 1 trial, the team extracted and isolated fibroblasts from the soles and scalps of 39 healthy volunteers. They then injected the purified cells into a small area of the patients’ thighs, about six millimeters in diameter. The transplanted cells were then removed and analyzed, leaving patients with only a small scar.
When given fibroblasts from their own soles, the patients’ thigh skin began to change. “You could feel in a lot of our subjects that it was a little more firm as you ran your finger across it,” Garza said. Subsequent analysis of the skin cells confirmed that the volar fibroblasts had survived the transplant and proliferated in their new home.
Garza emphasized that the transplant only partially transformed the thigh skin and that further fine-tuning is needed to perfect the procedure.
The team is now enrolling patients with amputated limbs, including veterans, in a randomized phase 2 trial where they will transplant a larger area of palm skin cells into residual limbs.
“Ultimately, the success of this work is not going to come from the scientists or clinicians but from people with amputations and how this may make life easier,” McGrath said.
Garza said other kinds of fibroblast transplants could hold promise, too. For example, skin types that grow hair better than others could be transplanted to treat hair-loss conditions like alopecia, he said. And volar fibroblasts could also be used to toughen up skin in other patients, like those who are bed-bound and suffer from pressure ulcers as a result.
To continue moving volar fibroblast cell therapy forward, Garza said his team is actively exploring potential industry options. “We are very excited to partner with industry, either as a startup or with a commercial partner with licensing,” he said. “We think there's a huge commercial potential here.”