On-chip construction of a fully structured scaffold-free vascularized renal tubule

Zhu, Yuntian; Shi, Zhengdi; Ding, Weiping; Li, Chengpan

doi:10.1007/s10544-023-00648-0

Cited by 1 publication

(1 citation statement)

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“…These include 3D cell culturing, 24,25 stem cell and organoid cultures, [26][27][28] 3D bioprinting, [29][30][31] and organ-on-achip technology. [32][33][34][35] Despite these advances, there is a demand for an in vitro model that integrates rapid and scalable readouts while maintaining physiological relevance. This should include features such as co-culture, fluid flow, and the absence of an artificial membrane to effectively study the proximal tubule in both health and disease.…”

Section: Introductionmentioning

confidence: 99%

An immunocompetent human kidney on-a-chip model to study renal inflammation and immune-mediated injury

Gijzen,

Bokkers,

Hanamsagar

et al. 2024

Preprint

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Kidney damage and dysfunction is an emerging health issue worldwide resulting in high morbidity and mortality rates. Numerous renal diseases are recognized to be driven by the immune system. Despite this recognition, the development of targeted therapies has been challenging as knowledge of the underlying mechanism and complex interactions remains insufficient. Recent advancements in the field offer promising avenues for exploring the interplay between renal cells and immune cells and their role in the development of renal inflammation and diseases. This study describes the establishment of a human immunocompetent 3Din vitroco-culture model of the proximal tubule in a high-throughput microfluidic platform that can be used to study renal functionality and inflammatory processes.The model incorporated RPTEC in the top compartment and HUVECs in the bottom compartment cultured under flow and in direct contact with a collagen-I ECM gel resulting in the formation of polarized tubular structures. As an immune component, human primary monocytes of different donors were added to the lumen of the endothelium. Renal inflammation was successfully induced using complement activated serum (CAS) as evident by epithelial morphological changes, increased expression of adhesion molecules, release of pro-inflammatory cytokines, and reduced epithelial viability. Realtime migratory behavior of monocytes showed increased extravasation and migration towards the ECM and Renal compartment upon exposure to CAS with donor-to-donor differences observed. Finally, immune modulatory compounds showed efficacious inhibition of monocyte migration under inflammatory conditions in the microfluidic co-culture model.A successful co-culture model was established and can be applied to study renal functionality in health and disease but also for drug screening due to the compatibility of the platform with automation and relatively high throughput. Overall, the described proximal tubule model has high potential to fill the gap that currently exists to study renal inflammation preclinically.

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