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Updated: May 9, 2026
Scalable Fabrication of Stretchable, Dual Channel, Microfluidic Organ Chips
Published on: October 20, 2018
Microfluidics meets organoids: Kidney and bladder-on-Chip models for preclinical drug delivery assessment
C Ma1, D Koh1, T Nishimura1
1Department of Micro Engineering, Kyoto University, Kyoto 615-8540, Japan.
Abstract:
High clinical attrition rates in drug development are frequently driven by unforeseen drug-induced nephrotoxicity, a challenge exacerbated by the profound interspecies differences and limited predictivity of conventional animal models. This translational gap is further compounded by the difficulty of recapitulating the complex, multilineage architecture of the human kidney and the stratified urothelial barrier of the bladder using traditional static cultures. Human induced pluripotent stem cell (hiPSC)-derived organoids integrated into microphysiological systems (MPS) offer a transformative opportunity to overcome these hurdles by merging human-specific biological complexity with precisely controlled engineering niches. In this review, we evaluate the evolution of kidney and bladder models from foundational platforms utilizing immortalized or primary cells to hiPSC-derived organoid-integrated chips, focusing on their quantitative capability to predict renal drug disposition and intravesical delivery. We detail the strategic integration of these human-relevant parameters into industrial physiologically based pharmacokinetic (PBPK) modeling and regulatory workflows. Furthermore, we highlight emerging synergies with multi-omics, computational "Digital Twins," and multidisciplinary engineering advances, including vascularization, real-time biosensing, and 3D bioprinting technologies with AI-guided automation for scalable, reproducible production. These platforms promise to transform preclinical assessment by delivering mechanistically precise, human-relevant data for de-risking therapeutics.
Insights
Human induced pluripotent stem cell (hiPSC)-derived organoids in microphysiological systems (MPS) enhance drug development by predicting kidney and bladder toxicity. These advanced models bridge the translational gap, improving therapeutic safety and efficacy.
Area of Science:
- Biotechnology
- Translational Medicine
- Drug Development
Background:
- High clinical attrition rates in drug development stem from unpredictable drug-induced nephrotoxicity.
- Conventional animal models and static cultures lack human kidney/bladder complexity and predictive power.
- Human induced pluripotent stem cell (hiPSC)-derived organoids within microphysiological systems (MPS) offer a solution.
Purpose of the Study:
- To review the evolution of kidney and bladder models, from basic platforms to hiPSC-organoid-integrated chips.
- To assess the quantitative predictive capabilities of these models for renal drug disposition and intravesical delivery.
- To explore the integration of these human-relevant models into physiologically based pharmacokinetic (PBPK) modeling and regulatory processes.
Main Methods:
- Evaluation of foundational cell-based models (immortalized/primary cells).
- Analysis of hiPSC-derived organoid-integrated microphysiological systems (MPS).
- Review of integration strategies with PBPK modeling, multi-omics, and engineering advances (vascularization, biosensing, 3D bioprinting, AI).
Main Results:
- hiPSC-organoid-integrated MPS models merge human biological complexity with engineering control.
- These advanced platforms offer quantitative prediction of renal drug disposition and intravesical delivery.
- Emerging technologies like multi-omics, Digital Twins, and AI-guided bioprinting enhance scalability and reproducibility.
Conclusions:
- hiPSC-organoid-integrated MPS represent a transformative approach to preclinical drug assessment.
- These human-relevant models provide mechanistically precise data for de-risking therapeutics.
- The integration of advanced engineering and computational tools promises to revolutionize drug development workflows.
