The annual International Society for Stem Cell Research (ISSCR) conference was held in Hamburg from July 10th to 13th and was a significant event for the stem cell academic and industrial community, bringing together over 4000 scientists from around the globe. The main topics included cell therapies, organoid technology, disease modelling, high-throughput target validation, cultivated meat, aging, and genome engineering. The ISSCR also organized discussion sessions on a forthcoming guidance document titled Clinical Standards | Best Practices for the Development of PSC-Derived Cellular Therapies, which promised to be key to standardize practices across indications and legal requirements. 

In the realm of biomedical research, including cell and gene therapy and cell bioprocessing, the integrity and consistency of cell lines are paramount. High-quality cell lines ensure reliable and reproducible results, which are critical for advancing scientific knowledge and therapeutic developments. Bionano’s OGM workflow was highlighted as a transformative tool for uncovering elusive structural variants (SVs) and copy number variants (CNVs) within edited and expanded cell lines. 

A key theme at ISSCR was the importance of correctly characterizing cell lines prior to their extensive use in drug development, disease modelling, and genetic research. The ISSCR webpage on genomic characterization emphasizes the importance of monitoring genetic integrity in stem cell cultures to prevent culture-acquired genetic changes that can impact cell behavior and research reproducibility. These changes can affect growth, tumorigenicity, differentiation potential, and data reliability. The guidelines recommend routine genetic assessments at various stages, including during the preparation of master and working cell banks, throughout experimental timelines, and after major interventions like reprogramming or gene editing. Therefore, robust quality control measures are essential to ensure the integrity of these cell lines. Common parameters to characterize are often: sterility, identify, purity, genetic profiling, tumorigenicity. 
 
Bionano’s OGM technology offers a unique and powerful solution to assess the integrity and stability of cell line. Unlike traditional methods, which might miss subtle but significant variations such as balanced translocations, OGM provides comprehensive and high-resolution genome mapping. OGM enables researchers to detect large structural variations, copy number variations, and other genomic aberrations with unprecedented accuracy. 

The power of OGM to uncover SVs and CNVs within stem cells that can be missed by traditional methods was shown in the 1-hour innovation showcase on Friday 12^th July in Hall G2. In this session it was highlighted how OGM provides a high resolution, genome-wide, sensitive, and reproducible solution to uncover cytogenetic changes that can alter many different aspects of stem cell phenotype and behavior.

Professor Emeritus Dr. Jeanne Loring from the Scripps Research Institute shared her expertise on iPSC culture and genome engineering. She previously shared some of her insights to improve the safety and integrity of cell therapies with optical genome mapping during an interview you can read here. Her talk focused on the use of OGM to assess the genomic stability and safety of iPSCs. She ended her talk recommending the use of OGM and NGS for a full genomic characterization of cell lines. Bionano has made the analysis of both techniques easier than never thanks to the VIA™ software, the only analysis software that combines secondary and tertiary analysis, receiving and interpreting data from optical genome mapping (OGM) and next-generation sequencing (NGS) to contextualize all classes of genomic variation and drive meaningful insights. 

Dr. Lucia Gallego from the Department of Molecular Biochemistry at Ruhr-University of Bochum presented findings from her recent publication in Cells. Genome editing with CRISPR/Cas9 has revolutionized genetic engineering, and when combined with human induced pluripotent stem cells (hiPSCs), it becomes a valuable tool in cerebral organoid research. During her talk and in their publication, she highlighted the importance of optical genome mapping in assessing genome integrity of CRISPR/Cas9-edited hiPSCs, emphasizing the need for thorough genomic and morphological analysis to ensure robust hiPSC-based models in cerebral organoid research.

Two posters were also presented during the event, highlighting the use of OGM in the cell and gene therapy application.  

The first poster introduced our high-throughput OGM instrument, the Stratys, designed for high-resolution, genome-wide structural variation detection. This instrument handles up to 12 samples simultaneously, significantly increasing throughput and reducing turnaround time. It showcased the detection of low variant allele fractions, providing an alternative to traditional methods like karyotyping and PCR. The system’s flexibility and high capacity make it suitable for genetic disease and cancer research and also cell line quality control, offering a robust tool for genome analysis. 

The second poster emphasized the use of OGM for assessing genome integrity in various applications, including cell and gene therapy, stem cell research, and bioprocessing. It highlighted the importance of maintaining genetic stability in cultured cells to ensure consistent quality and behaviour. OGM was shown to be highly sensitive and accurate in detecting structural variations, even at low variant allele fractions. The method benefited the monitoring of genetic integrity throughout different stages of cell line development and supported applications like CAR T cell production and iPSC research. By identifying genomic alterations that could impact research and therapeutic outcomes, OGM enhanced quality control in these fields. 

Overall, both posters underscored the efficacy and advantages of OGM in providing detailed genomic insights, improving throughput, and ensuring the reliability of cell-based products for research and therapy. 

The insights shared at ISSCR 2024 highlight how Bionano’s optical genome mapping technology represents a significant advancement in the quality control of cell lines. By providing detailed and accurate genome maps and high resolution of both SVs and CNVs, OGM ensures the integrity and reliability of cell lines, ultimately supporting better research and industrial outcomes.  

As expert Dr. Lucia Gallego states “As the rapidly expanding field of stem cell and cerebral organoid research advances, it is imperative that quality standards for genomic integrity evolve accordingly. Thorough verification of genomic integrity using advanced techniques is essential for producing reliable and replicable results. Therefore, optical genome mapping (OGM) might serve as a crucial complementary alternative to conventional genome quality control methods, offering high resolution and accuracy.” 

Explore how Bionano’s optical genome mapping can revolutionize your cell line quality control.