Tempo-iKidneyPod™ was mentioned in springer.com in a review article that summarized various investigative methods and applications of microfluidic chips, specifically to examine how SARS-CoV-2 causes acute kidney injury (AKI). Tempo-iKidneyPod™ is composed of human iPSC-derived kidney proximal tubules and podocyte cells in a 3D spheroid. The authors of the article cited Tempo-iKidneyPod™ as an accurate, patient-specific multi-cell model that can be used to examine the adverse and differing effects of SARS-CoV-2 infection on patients’ kidneys, in combination with microfluidic chips.
In this review article, researchers summarized and discussed the applications of microfluidic chips specifically in investigating acute kidney injury (AKI). Kidneys can experience adverse effects from diseases not specifically related to this organ. Additionally, AKI can be brought on by SARS-CoV-2 infections, which was found in 9.2% of all positive patients according to an April 2020 study. More importantly, this study found that 61.5% of patients with AKI needed intensive care. To investigate this correlation further, the authors proposed applications by which microfluidic chips could be utilized to better understand human kidney function and model after human diseases for the development of new treatments.
To mimic functional tubules, the authors suggested that characteristics such as shear stress – the friction force on the renal tubular cells – was difficult to model using traditional monolayer cell models. Furthermore, while immortalized kidney cell lines such as Madin-Darby Canine Kidney (MDCK) cells are used in proof-of-concept experiments traditionally, the lack of human-specific gene expression make MDCK cells less relevant compared to human iPSC-derived cells.
Additionally, to investigate the impact of SARS-CoV-2 on human cells, authors discussed the use of primary renal proximal tubule epithelial cells (RPTECs) which contain key kidney transporters that mediate the reuptake of glucose (GLUT2) and nutrients. Also, RPTECs contain ACE2-related genes that allow the spike protein of SARS-CoV-2 to bind, and thus can appropriately model infection. Furthermore, RPTECs are very sensitive to toxic effects from drugs, which is promising for drug metabolism studies. However, without patient specificity, RPTECs are only relevant for exploratory cell based assay studies.
To truly understand the cause of the wide impacts of SARS-CoV-2 on AKI, the authors proposed that 3D spheroid iPSC-derived cell products such as Tempo Bioscience’s Tempo-iKidneyPod™ have the capabilities to model complex functionalities of kidneys by including multiple cell types while offering a patient-relevant model.
3D Spheroid Relevance
As discussed in the previous section, several characteristics of kidney function must be maintained to accurately model the organ’s dynamics within a microfluidic chip. Maintaining the interconnectedness of the cell types present in kidneys in the form of a spheroid is essential, since the effectiveness of the kidney is dependent on the several complex interactions such as concentration gradients, absorption, and filtration.
In Cell of the Month: The Kidney, we outline the unique functions of podocytes, parietal epithelial cells, and renal proximal tubule epithelial cells. And, we describe the impacts on the kidney if any cell type loses its functionality. In combining these cell types, Tempo’s 3D spheroid offers researchers a human-specific appropriate model that better mimics the functionality of a kidney rather than isolated cell types. This allows researchers to create novel assays to evaluate kidney functions.
Drug Screening and Toxicology
The use of microfluidic chips and model organs can effectively indicate drug toxicity because microfluidic chips allow cells to exist in 3D and mimic “mini-organ” functionalities., and thus create the most accurate models to prevent unintended toxicity-related side effects in patients. In this study, authors discussed how RPTECs are highly sensitive to toxicity and thus are good indicators for drug metabolism studies.
Past studies using microfluidic chips with kidney-mimicking cells have explored the effects of drugs on monolayer formation and linking one organ to another organ. Monolayers contain only one cell type (for most cell based models). Hence, monolayers lack the complexity and functionalities represented by multi-cell type models. AKI caused by COVID has varying impacts on patients, so the patient-specific capabilities of microfluidic chip modeling could provide better understanding of these differences.
Tempo Bioscience Product Relevance
Tempo-iKidneyPod™ is a multi-cell type spheroid in 3D. Authors cited this product for its physiological relevance in modeling in vitro renal proximal tubule epithelium. While this study specifically references Tempo-iKidneyPod™ in relation to investigating AKI, authors also reference how microfluidic chips can be used to create novel ways to measure toxicity and fibrosis.