Kristina Runeberg on the Future of Stem Cells
We ask Takara Bio Europe AB’s Kristina Runeberg for her views on the use of stem cell in drug discovery. Kristina is the Site Head/ Senior Director of Business Development at Takara Bio Europe AB.
What are the main challenges in meeting GMP when dealing with stem cells?
Meeting the strict requirements from both the US Food and Drug Administration (FDA) as well as the European Medical Agency (EMA) regulations is challenging, specifically when obtaining proper donor testing and consent related to commercial therapeutic use of the donor cells. Additionally, iPSC and hES cell lines often contain animal- or human-derived components, or they are sourced from regions not accepted by the FDA. Secondly, a therapeutic dose is on the order of 109 cells, which requires scaling cells in a cost- and space-efficient manner. A third challenge concerns the culture of hiPS cells for clinical use. Researchers need to follow rigorous manufacturing standards to ensure quality and consistency. At Takara Bio, we offer GMP-grade cell culture products and we have the expertise and facilities required to generate clinical-grade human ES and iPS cell line services for therapeutic applications.
What is one issue facing scientists using stem cells in the field of drug discovery?
Presently, the generation of clonal cell lines following gene editing is difficult. This bottleneck occurs because hiPS cells are typically grown in colony culture, and re-plating as single cells greatly reduces viability. Promoting single-cell survival and proliferation is critical for expanding gene-edited clones. To address these challenges, we offer complete systems that combine CRISPR/Cas9 gene editing technology with our optimized Cellartis® DEF-CS™ single-cell culture system. These systems provide a new level of sophistication in cell biology research by allowing the isolation of single, edited iPS clonal lines that have been corrected for a specific mutation, followed by differentiation into novel cell types to develop more robust models to study disease
What techniques can be used to identify high-quality stem cells?
High-quality stem cells must exhibit high levels of pluripotency, have a robust growth rate, and maintain a stable karyotype over an extended time in culture. These characteristics can be achieved by culturing cells in a monolayer. Unlike other culture media products, the Cellartis DEF-CS system maintains these characteristics with a stable karyotype following more than 30 passages, ensuring that differentiation protocols start with a homogeneous population of high-quality iPS cells.
What advantages can patient-specific iPS cells offer drug discovery researchers?
Patient-derived iPS cell lines that recapitulate the human disease state can be powerful cellular models for high-throughput drug screening applications. Additionally, advances in gene editing technology make it possible to precisely add or eliminate specific mutations to validate a drug target and fine tune how accurately it models the disease. This means predictive, specifically tailored, disease-specific lines can speed up the process of drug discovery. To aid in this discovery, Takara Bio can source material from patients with specific biomarkers of disease and generate specific iPS lines using footprint-free Sendai virus technology.
What still needs to happen before iPS cell-based models become widely implemented in preclinical drug development?
Before cell-based models can become more widely implemented, researchers need to:
- Be certain that the iPSC-derived models are sophisticated enough to have the key characteristics of their in vivo analogues.
- Have robust systems for both maintaining pluripotency and directing differentiation that can be easily applied to any iPS or ES cell line.
- Have the ability to scale up enough cells to support high-throughput screening applications.
To meet these needs, we have developed iPS cell-derived hepatocytes, cardiomyocytes, and pancreatic beta cells that can be manufactured in a reproducible manner at industrial scale and miniaturized into 96-well or 384-well formats for compound screening.
What types of iPSC-derived models are ready to be adopted in preclinical development?
Because iPSC-derived cardiomyocytes were among the first types of cells to have robust differentiation protocols, iPSC-derived cardiomyocytes are starting to be implemented in some preclinical applications. Other areas that could benefit from iPSC-derived models are disease areas that rely on primary cell types that are fundamentally limited in batch size and donor availability—particularly type 2 diabetes and liver diseases. We specialize in some of these difficult cell types of the endoderm lineage, specifically, iPSC-derived beta cells and hepatocytes. We’ve shown that the newest version of our iPSC-derived hepatocytes possesses many metabolic-disease-relevant applications that should enable their use in the discovery stage of drug development.
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