Globally, millions of individuals suffer from debilitating pain. However, with remarkable 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 globe.
One key development is the creation of new cell-culture models for pharmaceutical researchers. Conventional in vitro models have used nerve cells derived from animal sources, usually the dorsal root ganglions (DRGs) of rats. Whilst these models remain useful for some purposes, they often produce results that are not well transferred into clinical studies.
Recent developments in stem cell biology now mean that it is possible for scientists to use physiologically relevant human sensory neurons in their research.
This article will explore the different benefits that human induced pluripotent stem cells (hiPSCs) provide when compared to cell-cultures derived from animals, and how hiPSC production could be a key technology in new research that has enhanced translation and impact.
Why are Animal-Derived Neuronal Cell-Cultures Losing Their Impact?
The main problem with using animal-derived neuronal cell-cultures is that the molecular mechanisms by which rodents experience pain are different to those in humans. For example, it has been found that human DRGs produce a tetrodotoxin-resistant (TTX-R) current that has not been observed in rodents.
For this reason, research into pain and drug discovery that uses animal cells could result in a translation barrier, making the occurrence of false positives when drug screening more likely. This has the knock-on effect of a higher cost and a higher risk in Phase I and II trials in humans.
How can hiPSC-Derived Sensory Neurons Overcome this?
Axol has used the latest developments in stem cell science to develop hiPSC- Derived Sensory Neuron Progenitors, which emulate the physiology and morphology of human sensory neurons in vivo. These hiPSC-Derived Sensory Neurons have been demonstrated as viable for human pain research by Axol’s external research partners.
Dr. Ramin Raouf and Natasha Rangwani, from Kings College London, found that hiPSCs show a calcium response in the presence of potassium chloride and capsaicin. This suggests that, like in human nociception, the cells have sodium and TRPV1 channels.
Dr. Edward Emery, from University College London, demonstrated that the hiPSC-Derived Sensory Neurons expressed cDNA that corresponds to the three voltage gated ion channels required for human pain perception (Nav1.7, 1.8 and 1.9). The neurons were also exposed to TTX and a TTX-R sodium current response was observed which corresponded to Nav1.8 and Nav1.9 – this is highly significant as this response has not yet been observed in rat cells.
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 hNav 1.7, hNav 1.8, and hNav 1.9 in Axol iPSC-derived sensory neurons. hNav 1.5 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. This suggested that both TRPV1 and sodium channels are present in these cells, emulating human pain perception.
New: Achieve Faster Maturation, Quicker Results and Enhanced Marker Expression.
MATURATION MAXIMIZER is a fully defined media supplement to enhance the existing sensory neuron maintenance medium (ax0060) and works by mimicking in-vitro, the cell to cell communication and interaction factors which occur when these cells are in their innate environment. The supplement is known to contain factors present in the peripheral nervous system and in particular the peripheral environment of sensory neurons."
How can You Start Using hiPSC-Derived Sensory Neurons in Your Research?
If researchers decide to start using hiPSC-Derived Sensory Neurons in their research they will be provided with an enriched population of hiPSC-Derived Sensory Neuron Progenitors which can be immediately cultured, giving them control over when to start their research.
Axol will also provide researchers with support throughout the culturing process. This is provided in the form of a cell-culture method and guidelines for using the MEA system, as well as access to their customer support team who can get in touch either on the phone or by video conference call.
In addition to this, Axol’s research partners have shared their top 5 pieces of advice on the culturing of hiPSC-Derived Sensory Neurons, to help researchers know what typically happens when their cell populations grow.
The use of hiPSC-Derived Sensory Neuron Progenitors over animal-derived cells makes the ethical research approval process easier. Axol has donor consent for all of their cell lines meaning animal research licenses are not required. In addition, their hiPSCs are sourced from one stable donor; meaning researchers are guaranteed consistency between batches and the validity of experiments will not be compromised should more cells be needed.
About AXOL Biosciences
Axol specializes in human cell culture.
Axol produces high quality human cell products and critical reagents such as media and growth supplements. We have a passion for great science, delivering epic support and innovating future products to help our customers advance faster in their research.
Our expertise includes reprogramming cells to iPSCs and then differentiating to various cell types. We supply differentiated cells derived from healthy donors and patients of specific disease backgrounds. As a service, we also take cells provided by customers (primary or iPSC) and then do the reprogramming (when necessary) and differentiation. Clearly, by offloading the burden of generating cells, your time is freed up to focus on the research. Axol holds the necessary licenses that are required to do iPSC work.
The package wouldn't be complete without optimized media, coating solutions and other reagents. Our in-house R&D team works hard to improve on existing media and reagents as well as innovate new products for human cell culture. We also supply a growing range of human primary cells; making Axol your first port of call for your human cell culture needs.
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