Human induced pluripotent stem cells (iPSCs) have revolutionized the way we approach disease modeling and drug discovery. But the journey from iPSCs to functional, disease-relevant cells is complex. At Axol, we’ve spent over a decade refining our approach to iPSC differentiation, and we’re committed to sharing that expertise to help accelerate progress in the broader scientific community.

In this article, we discuss the following:

• Custom iPSC Differentiation Expertise: Learn how we are leveraging over a decade of experience to produce high-quality, functional iPSC-derived cells that support more human-relevant disease models for your specific project.
• Motor Neuron Research Focus: Discover how our axoCells™ Motor Neurons are playing a critical role in ALS and other neurodegenerative disease models, accelerating drug discovery efforts.
• Accelerated Maturation Process: Explore how our innovative Accelerator Supplement reduces the maturation time of motor neurons from six weeks to just 10 days, without sacrificing quality or functionality.
• Characterization & Functional Validation: Understand the detailed phenotypic characterization and functional assays we use to ensure our motor neurons are ready for advanced in vitro models.
• Functional Quality Control (fQC): Learn more about our approach to functional QC, ensuring the physiological relevance of our cells and enhancing their translational power for drug development.

Perfecting iPSC Differentiation for Advanced In Vitro Systems

Differentiating iPSCs into the specialized cells needed to model human diseases requires not just technical expertise, but also a deep understanding of cellular biology. Whether it’s neurons for neurodegenerative diseases, cardiomyocytes for cardiotoxicity, or sensory cells for pain research, the cells need to be both functionally relevant and reproducible. This is never an easy thing to achieve. The risks and costs of getting it wrong can be significant but the potential for a better, smarter model system is invaluable.

At Axol, we offer a scalable approach to quality, functional cell manufacturing.

We can manufacture from our lines, your lines or third-party lines.

We can manufacture the following cell types:

• Cortical Excitatory Neurons
• Striatal Neurons
• Cortical Inhibitory Neurons
• Microglia
• Astrocytes
• Motor Neurons
• Sensory Neurons
• RPE
• Sebocytes
• Ventricular cardiomyocytes
• Atrial cardiomyocytes

Our Collaborative Approach to our axoServices

At Axol, our approach is built on collaboration with an obsession on quality. We understand the importance of open communication and transparency. From the outset, we work closely with our clients, whether they are researchers at academic institutions, small biotechs, or large pharmaceutical companies, to ensure that their needs are met with precision and care.

We offer custom manufacturing services, tailoring our iPSC-derived cell production to meet the unique requirements of each project. We’re not just delivering cells; we’re helping to build more accurate, more reliable disease models. This is where our expertise comes in. Our well-characterized iPSC lines, extensive quality control, and robust differentiation protocols ensure that the cells we provide are functional, consistent, and tailored to the specific needs of each project.

Focusing on Motor Neurons: A Key Cell Type for ALS Drug Discovery

One of the areas where we are particularly focused is in the production of iPSC-derived functional motor neurons. These cells are central to understanding neurodegenerative diseases like ALS, where the progressive destruction of motor neurons leads to debilitating loss of motor control. Our axoCells™ Motor Neurons are specifically designed to fuel advanced in vitro models of these conditions, and they play a crucial role in ALS drug discovery and neurodegenerative disease research.

In our ‘ALS Toolbox’, we presented characterization data from motor neurons differentiated from SOD1, TDP43, C9orf lines and matched unaffected donors.

Our motor neurons are extensively characterized for phenotypic relevance, ensuring correct morphology and expression of key markers such as HB9, MAP2, LIM3, and ChAT2. Additionally, we have developed an innovative Accelerator Supplement that mimics in vivo conditions, reducing maturation times for these motor neurons from six weeks to just 10 days. This accelerated process doesn’t sacrifice quality, these cells demonstrate full functionality and are ready for use in assays, including electrophysiology and calcium imaging, within just 10 days.

From Phenotypic Characterization to Functional Relevance

The utility of our axoCells™ Motor Neurons goes beyond morphology. We’ve validated their functionality through a range of biologically relevant assays. These include electrophysiology, which demonstrates the ability of the cells to generate action potentials and form functional networks, as well as calcium imaging, which provides insights into cellular responses to stimuli.

We are also pushing the boundaries of what’s possible in terms of functional quality control (fQC). As part of our ongoing commitment to advancing the field, we are developing new assays that measure the functional performance of our cells in biologically-relevant contexts. For instance, multi-electrode array assays are being used to assess synchronized burst firing, which is critical for functional network formation. This new standard of fQC enhances confidence in the physiological relevance of our motor neurons and strengthens the translational power of our models.

Empowering Neurodegenerative Disease Models

Neurodegenerative diseases, including ALS, Alzheimer’s Disease, and Huntington’s Disease, affect millions of individuals worldwide. As these diseases continue to rise, driven by an aging population and increasing comorbidities, there is an urgent need for new therapies. However, the current failure rate for new drug therapies is alarmingly high, around 99.6%. Animal models have provided some insights, but researchers are increasingly turning to human-relevant models to bridge the translational gap.

That’s where our iPSC-derived cells come in. We’ve developed a range of axoCells™ for use in neurodegenerative disease models, including healthy control and patient-derived motor neurons, which are ideal for ALS studies. These cells are phenotypically characterized, express key markers, and exhibit functionality across a variety of assays. They are also designed for advanced in vitro models, including microfluidic devices and organ-on-chip systems.

These advancements help accelerate the discovery of new therapies by providing a more accurate representation of human diseases, ensuring that drug candidates are tested in a system that closely mirrors human biology. With our motor neurons, researchers are equipped with reliable tools to explore the underlying mechanisms of disease and test potential treatments.

Strengthening the Community of iPSC Research

The challenges of iPSC differentiation are not unique to any one organization, they are shared across the scientific community. That’s why we believe that knowledge-sharing and collaboration are so important. We’re committed to not just being a service provider, but also an active participant in the growing iPSC ecosystem. By offering our expertise, we aim to help researchers overcome the barriers to developing better disease models and ultimately, better therapies.

Our work is driven by the belief that the best outcomes come from working together. Whether through informal discussions with researchers or more formal partnerships with biopharma and academic institutions, we strive to contribute to a wider network of expertise, helping to shape the future of human disease modeling.

Looking Ahead: A Shared Mission for Better Patient Outcomes

At Axol, we are passionate about the potential of iPSCs to transform how we model and treat human diseases. We know that this is just the beginning. There is still much to learn, refine, and discover. But with a collaborative, transparent approach to research, we believe we can make meaningful contributions to the scientific community and help bring better therapies to patients.

Just ahead is a new wave of diverse, patient stratification ‘clinical trial in a dish’ systems that will bring new opportunities to drug discovery.

We are excited to continue supporting our partners, sharing our knowledge, and advancing the field of iPSC-based disease modeling. Together, we can build more effective, human-relevant models that accelerate drug discovery and move us closer to improved patient outcomes.

To find out more about our custom manufacturing services, please contact us at operations@axolbio.com. We’ll be happy to have a conversation.