The ?? ??? ?? ??complications of the little boy’s genetic skin disease grew as he did. Tiny blisters had covered his back as a newborn. Then came the chronic skin wounds that extended from his buttocks down to his legs.

By June 2015, at age 7, the boy had lost nearly two-thirds of his skin due to an infection related to the genetic disorder junctional epidermolysis bullosa, which causes the skin to become extremely fragile. There’s no cure for the disease, and it is often fatal for kids. At the burn unit at Children’s Hospital in Bochum, Germany, doctors offered him constant morphine and bandaged much of his body, but nothing — not even his father’s offer to donate his skin — worked to heal his wounds.

“We were absolutely sure we could do nothing for this kid,” Dr. Tobias Rothoeft, a pediatrician with Children’s Hospital in Bochum, which is affiliated with Ruhr University. “[We thought] that he would die.”

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As a last-ditch effort, the boy’s father asked if there were any available experimental treatments. The German doctors reached out to Dr. Michele De Luca, an Italian stem cell expert who heads the Center for Regenerative Medicine at the University of Modena and Reggio Emilia, to see if a transplant of genetically modified skin cells might be possible. De Luca knew the odds were against them — such a transplant had only been performed twice in the past, and never on such a large portion of the body. But he said yes.

Original image has been replaced. Credit: Mashable

The doctors were ultimately able to reconstruct fully functional skin for 80 percent of the boy’s body by grafting on genetically modified cells taken from the boy’s healthy skin. The researchers say the results of this single-person clinical trial, published on Wednesday in Nature, show that transgenic stem cells can regenerate an entire tissue. De Luca told reporters the procedure not only offers hope to the 500,000 epidermolysis bullosa patients worldwide — but also could offer a blueprint for using genetically modified stem cells to treat a variety of other diseases.

A rapid recovery

To cultivate replacement skin, the medical team took a biopsy the size of a matchbook from the boy’s healthy skin and sent it to De Luca’s team in Italy. There, researchers cloned the skin cells and genetically modified them to have a healthy version of the gene LAMB3, responsible for making the protein laminin-332. They grew the corrected cultures into sheets, which they sent back to Germany. Then, over a series of three operations between October 2015 and January 2016, the surgical team attached the sheets on different parts of the boy’s body.

The gene-repaired skin took, and spread. Within just a month the wounds were islands within intact skin. The boy was sent home from the hospital in February 2016, and over the next 21 months, researchers said his skin healed normally. Unlike burn patients — whose skin grafts aren’t created from genetically modified cells — the boy won’t need ointment for his skin and can regrow his hair.

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The gene-repaired skin took, and spread. Within just a month the wounds were islands within intact skin.

And unlike simple grafts of skin from one body part to another, “we had the opportunity to reproduce as much as those cells as we want,” said plastic surgeon Dr. Tobias Hirsch, one of the study’s authors. “You can have double the whole body surface or even more. That’s a fantastic option for a surgeon to treat this child.”

Dr. John Wagner, the director of the University of Minnesota Masonic Children’s Hospital’s blood and marrow transplant program, told STAT the findings have “extraordinary” potential because, until now, the only stem cell transplants proven to work in humans was of hematopoietic stem cells — those in blood and bone marrow.

“They’ve proven that a stem cell is engraftable,” Wagner said. “In humans, what we have to demonstrate is that a parent cell is able to reproduce or self-renew, and differentiate into certain cell populations for that particular organ. This is the first indication that there’s another stem cell population [beyond hematopoietic stem cells] that’s able to do that.”

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The researchers said the aggressive treatment outlined in the study — necessary in the case of the 7-year-old patient — could eventually help other patients in less critical condition. One possibility, they noted in the paper, was to “bank” skin samples from infants with JEB before they develop symptoms. These could then be used to treat skin lesions as they develop rather than after they become life-threatening.

“The treatment might be more effective in children, whose stem cells have higher renewal potential and who have less total skin to replace, than in adults,” Mariaceleste Aragona and Cédric Blanpain, stem cell researchers with the Free University of Brussels, wrote in an accompanying commentary for Nature.

But De Luca said more research must be conducted to see if the methods could be applied beyond this specific genetic disease. His group is currently running a pair of clinical trials in Austria using genetically modified skin stem cells to treat another 12 patients with two different kinds of epidermolysis bullosa, including JEB.

For the 7-year-old boy, life has become more normal now that it ever was before, the researchers said. He’s off pain meds. While he has some small blisters in areas that didn’t receive a transplant, they haven’t stopped him from going to school, playing soccer, or behaving like a healthy child.

“The kid is doing quite well. If he gets bruises like small kids [do], they just heal as normal skin heals,” Rothoeft said. “He’s quite healthy.”

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