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Liu Qi, Zhang Ruzhi. Third Affiliated Hospital of Soochow University, Suzhou 213003, China Corresponding author: Zhang Ruzhi, Email: zhangruzhi628@163.com ��Abstract�� Recessive dystrophic epidermolysis bullosa ��RDEB��, an inherited blistering disease caused by mutations in the gene encoding type �� collagen, has a strong impact on patients′ quality of life. At present, it is mainly managed by symptomatic treatment, and more effective therapeutic approaches are urgently needed. Recent studies have found the presence of patches of normal-looking skin caused by reverse mutations in patients with RDEB. This phenomenon is called revertant mosaicism, also known as “natural gene therapy”. This finding offers the possibility of revertant cell therapy, namely, transplantation of revertant keratinocytes cultured in vitro onto damaged skin. The combination with patient-specific induced pluripotent stem cells ��iPSCs�� makes it possible to harvest large sheets of healthy skin graft. Moreover, iPSCs derived from revertant keratinocytes can differentiate into hematopoietic cells and mesenchymal stem cells, which can home to blistering areas after bone marrow transplantation, namely, “from skin to blood cells, then to repair of skin”.

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