LB1616 EpiX™ expansion technology enables in vitro tissue engineering of skin using autologous patient-derived cells for regenerative medicine applications
JOURNAL OF INVESTIGATIVE DERMATOLOGY(2018)
摘要
It remains a challenge to preserve stem and progenitor cells during expansion of epidermal keratinocytes ex vivo under serum-free and feeder-cell-free culture condition. This limitation greatly hinders the development of advanced autologous cell and gene therapeutics for inherited skin diseases such as epidermolysis bullosa and injuries such as severe burns. We have developed a serum-free and feeder-cell-free culture technology (EpiX™) that allows rapid generation of more than one-trillion epidermal keratinocytes while retaining the stem and progenitor cell population. In-depth whole genome sequencing and in vivo tumorigenicity studies demonstrated that the EpiX™-expanded cells maintain genetic stability. The preservation of stem cell character is evidenced by repeated single cell cloning capability to enrich genetic engineered cells via CRISPR/Cas9-mediated gene knock-in into the AAVS1 safe harbor locus. EpiX™-expanded keratinocytes maintain basal cell phenotype during ex vivo expansion and readily differentiate into the stratified epidermis in organotypic culture on the air-liquid interface. When grafted into immunocompromised mice, human keratinocytes survived over several months in vivo and seamlessly integrated with wounded mouse skin. An improved manufacturing process allows us to make suturable clinical-sized (75 cm2) skin graft sheets with mesenchymal-cell-populated dermis and stratified epidermis layers, thereby enabling the development of a range of gene-engineered cellular therapeutics for diseases and injuries of the skin.
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关键词
tissue engineering,regenerative medicine applications,lb1616 epix™,vitro,patient-derived
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