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Development of a blood-retina barrier on-a-chip with human iPSC-derived retinal pigment epithelium and endothelium

Marrero Feitosa-Afonsso, D. (2019) Development of a blood-retina barrier on-a-chip with human iPSC-derived retinal pigment epithelium and endothelium.

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Abstract:Age-related macular degeneration (AMD) is a complex and multifactorial disease that causes irreversible central vision loss in the elderly, affecting 170 million people worldwide. The key tissue implicated in the disease is the outer blood-retina barrier (oBRB) composed of the retinal pigment epithelium (RPE), Bruch’s membrane, and the choriocapillaris. Despite its high prevalence, the exact cause and onset of the disease remain largely unknown. This is mainly due to the inability of current models to recapitulate the multilayered architecture of the oBRB and capture relevant differences in genetic and environmental variability amongst patients. Therefore, the aim of this research project is to develop a physiologically relevant oBRB-on-a-chip model by mimicking the microenvironment of the RPE-choroid interface in vitro with stem cell-derived material. The oBRB architecture was emulated with a co-culture of hiPSC-derived RPE seeded on an open-top chamber interfaced with hiPSC-derived endothelial cells (ECs) embedded into a collagen patterned microchannel. The two generated hiPSC-derived cell types displayed characteristic features of mature and functional cells such as polarized VEGF secretion and angiogenic potential by the RPE and ECs, respectively. Moreover, the ECs in co-culture with the RPE cells expressed the vascular endothelial cadherin marker after three days of culture. This work demonstrates that the co-culture of hiPSC-derived RPE and ECs is compatible with OoC technology and establishes a model for future study of in vitro cellular and molecular mechanisms of the RPE-choroid interface.
Item Type:Essay (Master)
Clients:
Radboudumc, Nijmegen, Netherlands
Faculty:TNW: Science and Technology
Subject:42 biology, 44 medicine, 51 materials science
Programme:Biomedical Engineering MSc (66226)
Link to this item:http://purl.utwente.nl/essays/79795
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