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Adv. Healthc. Mater., Mar 07 2024, | https://doi.org/10.1002/adhm.202400405
Efficient Generation of Skin Organoids from Pluripotent Cells via Defined Extracellular Matrix Cues and Morphogen Gradients in a Spindle-Shaped Microfluidic Device
Cristina Quílez#1,2,3, EunY. Jeon#,†1, Alberto Pappalardo1, Pooja Pathak1, and Hasan E.Abaci*1,4
1Department of Dermatology, Columbia University Irving Medical Center, New York, NY, 10032, USA.
2Department of Bioengineering, Universidad Carlos III de Madrid, Leganés, 28911, Spain.
3Fundación Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Madrid, 28040, Spain.
4Department of Biomedical Engineering, Columbia University, New York, NY, 10032, USA.
#Authors equally contributed to the study.
†Present address: Research Group of Food Processing, Korea Food Research Institute, Wanju 55365, Republic of Korea
*Correspondence: Hasan E. Abaci
Abstract
Pluripotent stem cell-derived skin organoids (PSOs) recently emerged as a developmental skin model that is self-organized into multiple components, such as hair follicles. Despite their impressive cellular and anatomical complexity, PSOs are currently generated in the absence of 3D extracellular matrix (ECM) signals and have several major limitations, including an inverted anatomy (e.g., epidermis inside/dermis outside). In this work, we established a method to generate PSOs effectively in a chemically-defined 3D ECM environment. After examining various dermal ECM molecules, we found that PSOs generated in collagen type I supplemented with laminin 511 exhibit increased growth compared to conventional free-floating condition, but fail to induce complete skin differentiation due in part to necrosis. We addressed this problem by generating the PSOs in a 3D bioprinted spindle-shaped hydrogel device, which constrains organoid growth longitudinally. This new culture system significantly reduced organoid necrosis, and led to a two-fold increase in keratinocyte differentiation and an eight-fold increase in hair follicle formation. Finally, we adapted the system as a microfluidic device to create asymmetrical gradients of differentiation factors, and improved spatial organization of dermal and epidermal cells. Our study highlights the pivotal role of ECM and morphogen gradients in promoting and spatially-controlling skin differentiation in the PSO framework. This article is protected by copyright. All rights reserved.
논문정보
- Research article
- 2024년 03월 (BRIC 등록일 2024-03-13)
- 국외 연구진
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