Organ Model: Urinary System

Synopsis

Organ-on-a-Chip technology is emerging as a powerful New Approach Methodology (NAM) for drug development, driven by the need for more human-relevant and scalable experimental models. As these systems move toward broader adoption, a key challenge remains: generating consistent, interpretable data that supports confident experimental and translational decision-making.

This webinar examines how imaging and AI-driven analysis workflows enable Organ-Chip studies to scale from innovation to routine application. Speakers begin with an overview of Organ-on-a-Chip technology and its role in addressing translational gaps in drug discovery, highlighting how Liver-Chips are being evaluated in collaboration with regulatory agencies for better prediction of drug-induced liver injury.

The session then explores how the newly released AVA™ Emulation System enables scalable Organ-Chip experimentation through an integrated system for incubation, microfluidic delivery, and routine imaging. Paired with AI-driven analysis, brightfield image data can be used to automate quality control by monitoring chip health, morphology, and assay performance over time across large studies.

To complete the workflow, post-study high-resolution imaging is applied to evaluate more complex biological markers, including toxicology-relevant endpoints and drug uptake. These datasets are paired with advanced analysis techniques that translate imaging data into quantitative, biologically meaningful insights.

Attendees will gain a practical understanding of how unified imaging and analysis strategies—spanning routine QC through advanced interrogation—support scalability, reproducibility, and alignment with evolving regulatory expectations for Organ-Chips and other NAM-based drug development.

With over 130 peer-reviewed publications across 30+ organ models, Emulate Organ-Chips are empowering researchers to make game-changing scientific breakthroughs! Download this digest to easily explore all publications related to your field of research, or to just learn more about how the technology itself is developing.

New this quarter:

Brain

• Modeling neurovascular dysfunction in Alzheimer’s disease using an isogenic brain-chip model

Lung

• Mechanical strain exacerbates Pseudomonas infection in an organoid-based pneumonia-on-a-chip model

Mouth

• A preliminary model of an oral dysplastic lesion on a chip

Vasculature

• Human coronary artery organ-chip with circulating immune cells recapitulates anti-inflammatory effect of pulsatile wall strain

In this webinar, Emeli Chatterjee, Postdoctoral Researcher at Massachusetts General Hospital, and Ben Swenor, Senior Science Liaison at Emulate, present case studies from three peer-reviewed papers highlighting how Organ-Chips have been used to study cardiorenal syndrome, environmental enteric dysfunction (EED), and immunotherapy safety. View now to learn how Organ-Chips can be used to investigate complex disease mechanisms and evaluate immunotherapy safety.

Case study topics include: 

• Cardiorenal Syndrome: Investigating the role of extracellular vesicles from patients with cardiorenal syndrome on renal injury using the Kidney-Chip, offering insights into disease mechanisms and potential therapeutic targets. 
• Immuno-oncology Safety: Using the Colon Intestine-Chip and Duodenum Intestine-Chip to evaluate the on-target, off-tumor safety of T-cell bispecific antibodies. 
• Environmental enteric dysfunction (EED): Replicating EED disease mechanisms with the Duodenum Intestine-Chip, comparing the effects of malnutrition with healthy vs. patient-derived tissue to uncover novel therapeutic targets. 

Read the author Q&A here.

Organ Model: Kidney (Glomerulus)

Application: Model Development

Abstract: Early developmental programming involves extensive cell lineage diversification through shared molecular signaling networks. Clinical observations of congenital heart disease (CHD) patients carrying SMAD2 genetic variants revealed correlations with multi-organ impairments at the developmental and functional levels. For example, many CHD patients present with glomerulosclerosis, periglomerular fibrosis, and albuminuria. Still, it remains largely unknown whether SMAD2 variants associated with CHD can directly alter kidney cell fate, tissue patterning, and organ-level function. To address this question, we engineered human iPS cells (iPSCs) and organ-on-a-chip systems to uncover the role of pathogenic SMAD2 variants in kidney podocytogenesis. Our results show that abrogation of SMAD2 causes altered patterning of the mesoderm and intermediate mesoderm (IM) cell lineages, which give rise to nearly all kidney cell types. Upon further differentiation of IM cells, the mutant podocytes failed to develop arborizations and interdigitations. A reconstituted glomerulus-on-a-chip platform exhibited significant proteinuria as clinically observed in glomerulopathies. This study implicates CHD-associated SMAD2 mutations in kidney tissue malformation and provides opportunities for therapeutic discovery in the future.

Organ Model: Kidney (Glomerulus)

Application: Model Development

Abstract: Organ-on-chip (OOC) systems are revolutionizing tissue engineering by providing dynamic models of tissue structure, organ-level function, and disease phenotypes using human cells. However, nonbiological components of OOC devices often limit the recapitulation of in vivo–like tissue-tissue cross-talk and morphogenesis. Here, we engineered a kidney glomerulus-on-a-chip that recapitulates glomerular morphogenesis and barrier function using a biomimetic ultrathin membrane and human-induced pluripotent stem cells. The resulting chip comprised a proximate epithelial-endothelial tissue interface, which reconstituted the selective molecular filtration function of healthy and diseased kidneys. In addition, fenestrated endothelium was successfully induced from human pluripotent stem cells in an OOC device, through in vivo–like paracrine signaling across the ultrathin membrane. Thus, this device provides a dynamic tissue engineering platform for modeling human kidney–specific morphogenesis and function, enabling mechanistic studies of stem cell differentiation, organ physiology, and pathophysiology.

Webinar Abstract

Featured session at Boston MPS Day, which took place on November 1, 2023.

Dr. Saumya Das from Massachusetts General Hospital (MGH) discusses using Organ-on-a-Chip platforms to study how extracellular vesicles (EVs) influence functional biology and disease mechanisms, particularly in cardiometabolic contexts. EVs, including exosomes and other small vesicles, are significant mediators of intercellular communication, carrying microRNAs, proteins, and other cargo that can alter recipient cell behavior. However, understanding their organ-specific effects in humans has been challenging due to limited animal models and difficulties in isolating human tissues under well-controlled conditions.

Leveraging Emulate’s Human Emulation System, Dr. Das’s team focuses on modeling complex human pathologies involving multiple organs, including the kidney, liver, heart, and potentially the brain. He highlights four case studies:

1. Cardiorenal Syndrome (Kidney-Chip):
   Cardiorenal syndrome involves kidney injury triggered by heart failure and volume overload. Dr. Das’s lab isolated patient-derived EVs and perfused them through the Emulate Kidney-Chip (proximal tubule epithelium and endothelial channels). EVs from patients with cardiorenal syndrome induced significant renal injury markers compared to EVs from heart failure patients without renal involvement or from healthy controls. Through multi-omics analyses (particularly microRNA profiling), they identified EV-contained microRNAs that modulate TGF-β signaling and drive kidney injury. Inhibition experiments confirmed that these microRNAs were both necessary and sufficient to replicate the disease phenotype, offering new mechanistic insights and potential therapeutic targets.
2. Obesity-Related Liver Disease (Liver-Chip):
   Obesity-derived EVs (notably from adipose tissue) were introduced into a Liver-Chip model. By creating a non-alcoholic fatty liver disease (NAFLD)-like environment and adding adipose-derived EVs, they observed lipid droplet accumulation and transcriptomic changes reminiscent of NAFLD. This platform allows for in-depth study of how EVs from obese patients affect hepatic metabolism and gene expression, potentially guiding future treatments for metabolic liver diseases.
3. Organ Crosstalk via EVs:
   Dr. Das’s lab extended their Liver-Chip studies to investigate EV release dynamics and their effects on other organs. For instance, EVs secreted under NAFLD conditions can be introduced to human cardiomyocytes or other tissue chips (e.g., neural tissues) to dissect mechanisms of systemic metabolic and inflammatory signals.
4. Future Brain-Chip Studies:
   Planned investigations will explore neuroinflammation and obesity-related brain changes with a Brain-on-a-Chip model. The team aims to understand if EVs derived from diseased tissues (e.g., adipose or liver) contribute to neuroinflammation and cognitive dysfunctions.

Key learnings from this presentation include:

• Human-relevant EV studies: MPS models provide a controlled, species-matched environment to study patient-derived EVs without the confounding factors of animal models.
• Mechanistic insights: Using multi-omics and gene perturbation experiments on Kidney or Liver-Chips revealed critical microRNA-driven pathways (e.g., TGF-β in cardiorenal syndrome), illuminating novel disease mechanisms and potential intervention points.
• Complex disease modeling: Combining EV treatments with disease-specific conditions (e.g., heart failure, NAFLD) on chips simulates human organ crosstalk and systemic pathophysiology, allowing exploration of how EVs contribute to multi-organ disorders.
• Personalized and translational research: With patient-derived EVs and chips modeling key human organs, researchers can identify actionable targets and biomarkers, bridging fundamental biology with clinical implications for complex cardiometabolic diseases.

Organ Model: Kidney (Glomerulus)

Application: Model Development

Abstract: The function of the glomerulus depends on the complex cell-cell/matrix interactions and replication of this in vitro would aid biological understanding in both health and disease. Previous models do not fully reflect all cell types and interactions present as they overlook mesangial cells within their 3D matrix. Herein, the development of a microphysiological system that contains all resident renal cell types in an anatomically relevant manner is presented. A detailed transcriptomic analysis of the contributing biology of each cell type, as well as functionally appropriate albumin retention in the system, is demonstrated. The important role of mesangial cells is shown in promoting the health and maturity of the other cell types. Additionally, a comparison of the incremental advances that each individual cell type brings to the phenotype of the others demonstrates that glomerular cells in simple 2D culture exhibit a state more reflective of the dysfunction observed in human disease than previously recognized. This in vitro model will expand the capability to investigate glomerular biology in a more translatable manner by the inclusion of the important mesangial cell compartment.

Organ Model: Kidney (Proximal Tubule)

Application: Inflammation

Abstract: Background: Cardiorenal syndrome (CRS) – renal injury during heart failure (HF) – is linked to high morbidity. Whether circulating extracellular vesicles (EVs) and their RNA cargo directly impact its pathogenesis remains unclear. Methods: We investigated the role of circulating EVs from patients with CRS on renal epithelial/endothelial cells using a microfluidic kidney-on-chip (KOC) model. The small RNA cargo of circulating EVs was regressed against serum creatinine to prioritize subsets of functionally relevant EV-miRNAs and their mRNA targets investigated using in silico pathway analysis, human genetics, and interrogation of expression in the KOC model and in renal tissue. The functional effects of EV-RNAs on kidney epithelial cells were experimentally validated. Results: Renal epithelial and endothelial cells in the KOC model exhibited uptake of EVs from patients with HF. HF-CRS EVs led to higher expression of renal injury markers (IL18, LCN2, HAVCR1) relative to non-CRS EVs. A total of 15 EV-miRNAs were associated with creatinine, targeting 1,143 gene targets specifying pathways relevant to renal injury, including TGF-? and AMPK signaling. We observed directionally consistent changes in the expression of TGF-? pathway members (BMP6, FST, TIMP3) in the KOC model exposed to CRS EVs, which were validated in epithelial cells treated with corresponding inhibitors and mimics of miRNAs. A similar trend was observed in renal tissue with kidney injury. Mendelian randomization suggested a role for FST in renal function. Conclusion: Plasma EVs in patients with CRS elicit adverse transcriptional and phenotypic responses in a KOC model by regulating biologically relevant pathways, suggesting a role for EVs in CRS.

OVERVIEW

The Proximal Tubule Kidney-Chip S1 BioKit includes the essential components needed to create the Proximal Tubule Kidney-Chip S1—including Emulate qualified cells—and is available in multiple sizes to meet various study needs.

Webinar Abstract

Predicting drug-induced kidney toxicity and drug-drug interactions during preclinical development continues to be challenging due to a researchers’ reliance on immortalized cell lines and animal models that do not translate to human response. These translational issues have real-world impacts in the clinic, with nephrotoxicity causing preclinical attrition and an estimated 19% of failures during phase 3 clinical trials¹. 

The Emulate Proximal Tubule Kidney-Chip has been developed to address these challenges, enabling researchers to more accurately model nephrotoxicity and drug-drug interactions to improve clinical success. By incorporating primary human kidney epithelial cells with tissue-specific endothelium in a dynamic microenvironment, the Proximal Tubule Kidney-Chip achieves a proper kidney phenotype exhibiting normal epithelial cell polarity and morphology and demonstrating in vivo-relevant functional transporter activity. 

View this data-driven webinar to learn how you can use Organ-on-a-Chip technology to overcome the limitations of conventional kidney models and gain more confidence before taking your drug candidate into the clinic. 

Key Advantages of the Proximal Tubule Kidney-Chip:   

• Retains characteristic kidney functionality for up to 14 days 
• Improved cytoarchitecture, polarization, and kidney marker expression due to a dynamic microenvironment  
• Improved functionality of key renal transporters (Megalin, Cubulin, P-gp, MATE1, MATE2-K, OAT1, OAT3, and OCT2, and more)  
• Demonstrated ability to model drug-induced nephrotoxicity and renal transporter-mediated drug-drug interactions