이정운 (한국생명공학연구원)

한빛사논문

조회413

한국생명공학연구원

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Biomaterials, Feb 23 2024, 307 S0142-9612(24)00056-5 | https://doi.org/10.1016/j.biomaterials.2024.122522 Development of pluripotent stem cell-derived epidermal organoids that generate effective extracellular vesicles in skin regeneration

Sojung Kwak ^a, Cho Lok Song^a, Jinhyuk Lee ^b,c, Sungyeon Kim ^d, Seungyoon Nam ^d,e, Young-Jun Park ^b,f, Jungwoon Lee ^a,b

^aDevelopmental Biology Laboratory, Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea

^bDepartment of Bioscience, KRIBB School, University of Science and Technology, Daejeon 34141, Republic of Korea

^cDisease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea

^dDepartment of Genome Medicine and Science, AI Convergence Center for Medical Science, Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Republic of Korea

^eDepartment of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences and Technology, Gachon University, Incheon 21999, Republic of Korea

^fEnvironmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea

Corresponding author : Jungwoon Lee

Abstract

Cellular skin substitutes such as epidermal constructs have been developed for various applications, including wound healing and skin regeneration. These cellular models are mostly derived from primary cells such as keratinocytes and fibroblasts in a two-dimensional (2D) state, and further development of three-dimensional (3D) cultured organoids is needed to provide insight into the in vivo epidermal phenotype and physiology. Here, we report the development of epidermal organoids (EpiOs) generated from induced pluripotent stem cells (iPSCs) as a novel epidermal construct and its application as a source of secreted biomolecules recovered by extracellular vesicles (EVs) that can be utilized for cell-free therapy of regenerative medicine. Differentiated iPSC-derived epidermal organoids (iEpiOs) are easily cultured and expanded through multiple organoid passages, while retaining molecular and functional features similar to in vivo epidermis. These mature iEpiOs contain epidermal stem cell populations and retain the ability to further differentiate into other skin compartment lineages, such as hair follicle stem cells. By closely recapitulating the epidermal structure, iEpiOs are expected to provide a more relevant microenvironment to influence cellular processes and therapeutic response. Indeed, iEpiOs can generate high-performance EVs containing high levels of the angiogenic growth factor VEGF and miRNAs predicted to regulate cellular processes such as proliferation, migration, differentiation, and angiogenesis. These EVs contribute to target cell proliferation, migration, and angiogenesis, providing a promising therapeutic tool for in vivo wound healing. Overall, the newly developed iEpiOs strategy as an organoid-based approach provides a powerful model for studying basic and translational skin research and may also lead to future therapeutic applications using iEpiOs-secreted EVs.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-03-06)
연구진국내 연구진
분야 생명과학 > 생화학

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