Millions of people around the world suffer from debilitating pain. However, with impressive advances being made in pain research and drug discovery efforts, researchers are continuing to delve deeper into the molecular pathways underpinning pain, to ultimately improve both the screening of drug candidates and the quality of life for people across the world.
One particularly exciting development has been in relation to the advances in cell-culture models available to drug discovery researchers. Traditional in vitro models have used animal-derived neurons (usually rat dorsal root ganglions), which, although valuable, make it difficult to translate experimental findings to the clinic. Thanks to recent innovations in stem cell biology, it is now possible to use physiologically relevant human sensory neurons in a research setting.
Read on to find out about the many advantages that human induced pluripotent stem cells (hiPSCs) offer over animal-derived cell-cultures, and how they could be the crucial tool to make breakthrough discoveries and improve the translation and impact of your research.
Why are animal-derived neuronal cell-cultures losing their impact?
The main issue is that the molecular pathways underpinning pain in rodents are different to those of humans. For example, research has shown that human dorsal root ganglion neurons have been found to produce a tetrodotoxin-resistant (TTX-R) current that has not been identified in rodents.
As such, pain research and drug screening based on animal cell pathways may present a translational barrier, heightening the chances of obtaining false positive results in the screening of drug candidates, and potentially leading to increased risk and cost in downstream human clinical trials.
How can hiPSC-Derived Sensory Neurons overcome this?
Here at Axol, we’ve harnessed the latest innovations in stem cell technology to produce hiPSC- Derived Sensory Neuron Progenitors, that replicate the morphology and physiology of human sensory neurons in vivo. But don’t just take our word for it, as our external research partners have also demonstrated the viability of these hiPSC-Derived Sensory Neurons in modeling human pain perception.
Dr Edward Emery of University College London showed that the hiPSCs expressed cDNA for all three voltage gated ion channels essential for human nociception (Nav1.7, Nav1.8 Nav 1.9). In addition, Dr Emery treated the sensory neurons with TTX and measured a TTX-R sodium current indicative of sodium channels Nav1.8 and Nav1.9 (which, crucially, is yet to be identified in rat models).
cDNA from iPSC-Derived Sensory Neuron Progenitors cultured for 8 weeks was compared to cDNA from human tissue from the dorsal root ganglion (DRG). PCR analysis confirmed the mRNA expression of hNav1.7, hNav1.8, and hNav1.9 in Axol iPSC-derived sensory neurons. hNav1.5 was included as a negative control. Data provided by Dr Edward Emery (University College London).
Dr Ramin Raouf and Natasha Rangwani of Kings College London identified that the hiPSC-Derived Sensory Neurons also elicited a calcium response when treated with capsaicin and potassium chloride suggesting both TRPV1 and sodium channels are present in these cells, replicating human pain perception.
How can you start using hiPSC-Derived Sensory Neurons in your research?
If you decide to make the switch, you will be provided with an enriched population of hiPSC-Derived Sensory Neuron Progenitors to start culturing right away, giving you complete control over when you start your research.
Ongoing support will also be provided to help you culture the cells. At Axol, we provide you with a supplementary cell-culture protocol and MEA system guideline, along with advice from our customer support team, which includes phone consultations and video conference calls, to help you culture the cells in your own lab. On top of this, our research partners have also shared their five top tips on culturing hiPSC-Derived Sensory Neurons so you know exactly what to expect as your cells grow and proliferate.
Using hiPSCs also makes the ethical approval process easier than with animal-derived cells, as we already hold donor consent for all our cell lines, meaning you will no longer have to apply for animal research licenses. Importantly, our hiPSC-Derived Sensory Neurons originate from one stable donor, providing you with access to consistently standardized cells, ensuring the validity of your experiments will not be affected should you need additional cells.
To find out more about our hiPSC-Derived Sensory Neurons, and how they offer a viable model of human pain perception that could advance the translation and impact of your research, read our application note.