Unlocking the Potential of iPSCs: Expert Insights on Opportunities in Cell Therapy R&D
Nicola Bevan is no stranger to advanced cell models…and their high-maintenance requirements. As a manager in the BioAnalytics applications group at Sartorius, Nicola and her team develop novel applications covering popular and emerging fields. We talked with her about induced pluripotent stem cell (iPSC)-derived cell therapies and the workflow challenges scientists face.
This article is posted on our Science Snippets Blog
Why all the fuss over iPSCs?
Induced pluripotent stem cells, or iPSCs, have sparked a wave of innovation in regenerative medicine and cell therapy. These cells have the extraordinary ability to transform into any cell type in the human body, which has significant implications for treating a vast array of diseases— without the ethical concerns that come with embryonic stem cells.
One of the most compelling features of iPSCs is that they can be reprogrammed from a patient's own cells, also known as autologous cell therapy. This customization significantly diminishes the risk of the body rejecting the therapy.
While the promise of iPSCs is enormous, they do come with their share of complexities. The cost of developing these cells can be high, and they thrive and retain their pluripotent properties only under very specific conditions.
Here is our full interview with Nicola about using these cells in cell therapy development.
Question: Can you give a brief overview of the cell therapy development workflow?
Process development for iPSCs requires multiple steps. First, you need to isolate your primary cell of choice before expansion. Next, you reprogram these cells to induce pluripotency and then select the best clones. Gene editing may be required at this stage to imbue the cells with specific histocompatibility profiles.
After more clone selection and expansion steps you produce the master and working cell banks. Pluripotency must be continually assessed during this time.
At this point you can induce differentiation to produce the cell lineage of interest for your therapy. This is often a lengthy process that involves multiple technical steps and checks to make sure you have the right phenotype and function.
Finally, the system needs to be scaled up to produce enough sterile, functional product for clinical use.
Question: What are the biggest obstacles when it comes to developing iPSCs?
iPSCs are high maintenance, expensive and require constant monitoring to ensure they maintain pluripotency, viability and homogeneity. Long-term culture of iPSCs can result in genotypic and phenotypic heterogeneity, even in a cell line derived from a single source cell. So, it is vital that you develop methods for monitoring, detecting, and reducing heterogeneity in iPSC lines.
The increasing use of stem cells in clinical and research settings calls for fast, robust, and cost-effective solutions for the growth, characterization, and maintenance of these valuable biological resources.
Question: Do you have any tips for successful process development for iPSC-derived cell therapies?
Certainly! You have to establish tight control of the whole process. This means ensuring good screening throughout, sufficiently optimizing each step to produce a homogenous and sterile product, and establishing a scalable production line.
One key way to achieve this is by automating as much of the process as possible to reduce variability and facilitate a higher throughput. You need screening systems that enable rapid process optimization, which is a big factor when scaling up. And as mentioned earlier, you must have the capability to continuously characterize iPSCs and derivatives throughout the differentiation process.
Finally, you need to set and monitor critical process parameters (CPPs) and critical quality attributes (CQAs) to measure the success of your process and enable seamless scale-up.
Question: What technologies do you use to address these challenges?
The best solutions should help you optimize differentiation protocols, accelerate process development, and implement consistent, high-quality manufacturing.
In the research and development stages, the Incucyte® Live Cell Analysis and iQue® Advanced Flow Cytometry platforms are powerhouses for characterizing cell phenotype and function at industry-level speed, depth, and scale. Also, for isolating single iPSC clones quickly and gently, nothing beats the flexibility and reliability of the CellCelector Platform.
Equally important are high-quality cell culture products and lab essentials for successful, sterile iPSC cultivation. Our research-use only (RUO) growth factors and cytokines support the expansion and differentiation of iPSCs, while the GMP growth factors and cytokines ensure a seamless transition from R&D to pre-clinical development and GMP manufacturing.
Of course, rapid and reliable kits for microbial detection are critical for contamination control throughout this process.
Question: If you could give one tip for streamlining the development of iPSC-derived cell therapies, what would it be?
I would say automation. Automated technologies reduce hands-on time and ultimately deliver you with safer, and more reliable products.
