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Using hiPSC-Derived Renal Proximal Tubular Cells in vitro assays to advance disease research and drug development

Michelle Ricketts

Using hiPSC-Derived Renal Proximal Tubular Cells in vitro assays to advance disease research and drug development

The rising numbers of kidney patients and a shortage of transplantable organs is a global health issue with high economic costs . Previous disease research and drug development has traditionally used animal models, but these fail to recapitulate human renal cellular function and so limit our ability to elucidate disease mechanisms and therapeutic targets.

Advances in stem cell biology over the last five years have transformed the state of play. Researchers are now able to access physiologically relevant renal cells and tissues derived from human induced pluripotent stem cells (hiPSCs), paving the way for therapeutic breakthroughs and novel applications.

One key application of human iPSC-derived renal proximal tubular cells (PTCs) is in safety toxicity testing during drug development . This is important because many pharmaceuticals can induce toxicity in the kidneys (nephrotoxicity), leading to impaired renal function and even death in the most severe cases. Now Axol have developed the first ready to use, commercially available hiPSC-derived Renal PTCs that have the potential to predict nephrotoxicity. This is providing researchers with access to high-quality, physiologically relevant renal cells for more efficient and reliable in vitro safety toxicity testing. Below we explore how hiPSC-derived Renal PTCs are not only advancing compound screening and drug development, but also have other exciting applications in kidney-related regenerative medicine, renal disease modelling, and the development of enhanced bioartificial kidneys.

How can human iPSC-derived Renal PTCs enhance drug development?

The major functional unit of the kidney (the nephron) largely relies on proximal tubular cells (PTCs), which are a key target for toxic pharmaceutical agents. A recent study has demonstrated the potential of hiPSC-derived renal PTCs in the assessment of nephrotoxicity. They evidently show great promise as a tool for accurately predicting human drug-induced nephrotoxicity in drug development, which conventional animal models are unable to do. This will help to decrease costs and risks during clinical trials, ensure regulatory compliance, and better protect patient health.

The hiPSC-derived PTCs recently developed by Axol are ready to use at the bench just four days after thawing. These cells will not only help to enhance the efficiency of your nephrotoxicity testing processes, but they can also offer a supply of high-quality, physiologically relevant cells to generate highly predictive nephrotoxicity assays essential to drug development.

Human iPSC-derived Renal Cells: Key applications and future opportunities

As well as being able to accurately predict nephrotoxicity, hiPSC-derived Renal PTCs could bring various other benefits to compound screening and drug development. This includes the ability to identify underlying injury mechanisms and drug-induced cellular pathways to inform therapeutic breakthroughs.

HiPSC-derived Renal PTCs are suitable for automated cellular imaging, so they could enable the efficient analysis of larger numbers of compounds. There are also exciting opportunities to use hiPSC-derived Renal PTCs in the development of novel personalized therapies and disease-specific in vitro models for compound screening and nephrotoxicity prediction .

The potential applications of hiPSC-derived Renal PTCs go beyond drug screening. A recent breakthrough is the generation of hiPSC-derived self-organising kidney tissue-like structures and kidney organoids in vitro , which is causing great excitement with respect to applications in kidney-related regenerative medicine and renal disease modelling , as well as in nephrotoxicology. Human iPSC-derived renal PTCs could also potentially solve some of the biggest problems with bioartificial kidneys , such as the identification of a reliable source for large numbers of PTCs that have a reproducible high quality.

Kidney disease research and drug development has previously relied on animal models that cannot recapitulate the normal function of human renal cells. As a result, our understanding of underlying disease mechanisms and therapeutic breakthroughs has been limited – until now.

With the recent emergence of hiPSC-derived renal PTCs, researchers now have access to physiologically relevant human cells and tissues to advance various applications, including nephrotoxicity screening during drug development.

Axol’s ready to use hiPSC-derived Renal PTCs now offer an efficient way of establishing in vitro toxicity screening platforms with a high predictivity and reproducibility to expedite and enhance your drug development research.

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