"Nature" headlines: stem cell treatment milestone "full body skin regeneration"
Release date: 2017-11-10
In the Ruhr Valley of Germany, a nine-year-old boy is enjoying his childhood: playing football, joking with friends, going to school. But what you can't think of is that two years ago, he was still in a hospital bed and was dying because of a rare and cruel hereditary skin disease. In a landmark online paper this week (November 9), a group of scientists and clinicians introduced the child's amazing healing details.
The boy has bullous epidermolysis (JEB), a serious genetic disorder that causes skin to loosen and is often fatal. Scientists believe that the cause of bullous epidermolysis is the mutation of LAMA3, LAMB3 or LAMC2, which affects laminin 332 (a component of the epidermal basement membrane), causing blisters and chronic wounds on the skin.
There is currently no good treatment for this disease, and doctors can only try to reduce his pain because 80% of his skin has been relaxed. Previous treatments in two patients have shown that transplanted transgenic epidermal cultures produce a functionally normal epidermis that repairs JEB skin lesions. But this is only to rebuild the skin within a small area.
Michele De Luca and others from the University of Modena in Italy have developed a method of combining stem cell technology with gene therapy to culture primary keratinocytes using skin cells without a bullous area on the boy's body, and then by retrovirus. The vector is genetically engineered to inhibit the non-mutated form of the LAMB3 gene, hoping to rebuild the skin.
Michele De Luca (corresponding author of this article) was a pioneer in skin rejuvenation in the 1980s, learning how to grow small pieces of skin from the cells of burn patients and transplant them. In the current study, he expanded his previous technique to develop stem cells from human skin, replace disease-causing genes, and grow healthy skin in the laboratory by combining new genetic and stem cell technologies. .
In 2015, a technology from the De Luca team was used in stem cell therapy to produce the world's first commercial stem cell therapy: Holoclar (for corneal treatment).
One day after a few months, De Luca received a call to invite him to treat the boy described above. He and the clinician gave the boy a skin biopsy, followed by two major skin grafts. . This transgenic epidermal graft is applied to the prepared dermal wound site to cover the affected body surface. After 6 months, the boy returned to school. In the next 21 months, the regenerated epidermis adhered tightly to the underlying dermis, and healed normally even after induction of mechanical stress. No bullae, boy Even began to show off his "new skin" to classmates.
This clinical breakthrough is based on basic research from previous decades, and the clinical data collected during the months of follow-up of the boy's treatment also helped to promote basic scientists' understanding of human skin biology, such as the epidermis. Normal regeneration is only guided by a small number of self-renewing stem cell clones that self-renew and produce progenitor cells that complement the terminally differentiated keratinocytes.
Patient skin cell cloning culture
At its root, highly personalized treatments may only be applicable to a certain group of patients. This study is aimed at the treatment of a patient, but this is a typical “standing on the shoulders of giantsâ€. For example, long-term follow-up of previous studies (2006), as well as parallel studies, paved the way for the success of this study.
This work is both a technical achievement and a model for how to transform medicine. The entire research process includes basic scientists, clinic clinicians, and their seamless cooperation on many levels has prompted the birth of this important outcome. Maybe the laboratory of other diseases can adopt a similar approach, and hope that there will be more in the future. The basic results are translated into the clinic and bring the gospel to the patients.
Original title
Regeneration of the entire human epidermis using transgenic stem cells
Source: Biopass
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