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Stepping up in drug development: moving from primary cells to human iPSCs

Stepping up in drug development: moving from primary cells to human iPSCs

MEA- Multi-Electrode Array axoServices

In the pursuit of robust, scalable disease models, iPSCs have enormous potential for drug discovery. While the long-standing use of cultured cells and primary cells has yielded valuable results, the persistently high trial failure rates have driven a search for alternatives. In this short article, we outline how transitioning from primary cells to human iPSCs can unlock rapid, scalable, and human-relevant disease models to accelerate and de-risk drug discovery.

Transitioning from primary cells to human iPSC models

Across the drug discovery process, researchers look to utilize more human-relevant models to test the efficacy and action of their therapy.

In early-stage research, the use of cultured and highly understood cell types (such as Human Embryo Kidney, or HEK cells and overexpressed gene cell lines) is commonplace, due to ease of access, licensing, handling, and cost. Primary cells, cells taken directly from living tissue and established for growth in vitro, are a common next step. As primary cells are taken from human tissue, they represent physiologically-relevant cell sources and can provide value for drug discovery.

However, there are a few key drawbacks to using primary cells:

  • Cell material can be difficult to obtain, especially for neurological cells
  • As human tissue is needed, there can be difficulties in accessing cell material in the volume and regularity needed for drug discovery
  • Primary cells can degrade over time

With a growing need for robust and scalable cell models, human iPSCs are positioned as the natural “next step” toward human-relevant models with the utility to match the scale needed for drug discovery.

Using human iPSCs for accessible, scalable disease models

Human iPSCs are stem cells with the capability of being differentiated into endpoint cells, such as neurons. The production of iPSCs starts from donated material from patients (most often blood samples) and provides a master ‘line’ from which a variety of cells can be produced in bulk – providing the connection between human origin and consistency.

Models built from human iPSCs can be scrutinized for physiological relevance and then used with defined, measurable assay endpoints to measure the therapeutic effect. A wide range of endpoints can be applied; from genomics to transcriptomics, proteomics, morphological assessment, and physiological outputs (for example, electrical activity in neurons).

There is a wide range of potential culture formats when building human iPSC models, across a spectrum of increasing complexity. They can be as simple as a 96-well plate containing a single cell type, assessing genomic changes in response to test compounds versus controls. On the other end of the complexity spectrum, iPSC-derived cells can be built into scalable microfluidic platforms to examine the interplay of neurons with neuroinflammatory cells in a more physiologically-relevant microenvironment. With increasing complexity comes a need for more technical expertise, but enables closer recapitulation of the in vivo state.

So while primary cells and human iPSCs both facilitate more human-relevant models compared to animal models, human iPSCs have key advantages: they are easily sourcedreadily available, more durable, and can be produced on far larger scales to support drug discovery. With high-quality, physiologically-relevant cells at the core of models, iPSCs are supporting biopharma on the drug discovery journey.

If you’d like to discuss how you can transition from primary cells to human iPSCs, speak to our expert scientists.

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