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Researchers across discovery and translational biomedicine recognize the critical importance of iPSCs in core applications beyond regenerative medicine. Large, global biobanks offer researchers unprecedented access to a diverse range of iPSC lines. However, not all iPSCs are created and maintained with equal adherence to quality standards. Understanding the difference between a high-quality iPSC line and one that may compromise your research investment is crucial for building successful projects and potential therapies. The quality of an iPSC line is contingent on a continuum of factors from sourcing and generation to storage and transportation infrastructure.

Donor diversity

While iPSCs can be differentiated into virtually any cell type, this does not mean they represent every human population. All iPSCs retain the global genetic landscape of their original donor and bear individual and clinically relevant genetic markers linked to factors such as sex and ethnicity. Therefore, iPSC research can suffer from the same biases as other areas of inquiry, as has been documented in genomic databases, where European ancestries have historically been overrepresented. A bank of iPSCs from diverse donors can provide more representative research, which in turn may yield therapies that serve wider populations.

Differential potential

The greater the number of cellular states an iPSC, or set of iPSCs, can be used to generate, the greater their potential value. In translational work, researchers can use genetically matched iPSCs to assess a drug’s efficacy on target cell types (e.g., neurons) while evaluating toxicity in cells such as cardiomyocytes, or to develop patient-specific models of diseases that affect multiple tissues. Switching to discovery, in a paper published in Nature Communications by Quaid et al. earlier this year, researchers describe the use of iPSCs to generate neural stem cells, motor neurons, and monocytes from single donors, allowing them to assess epigenetic mechanisms governing cell type while controlling for the noise of genetic and environmental variations. Differentiation consistency is also crucial, as reliable differentiation protocols enable reproducible research and efficient therapeutic development at scale.

Repositories that maintain cells with diverse differentiation potential include:

• The National Institute of Neurological Disorders and Stroke (NINDS) Human Cell and Data Repository
• The National Institute of Mental Health (NIMH) Repository and Genomics Resource
• The European Bank for Induced Pluripotent Stem Cells (EBiSC)
• Simons Foundation Autism Research Initiative (SFARI) Repository

Genomic stability

Genomic stability ensures cells continue to function as intended. Loss of stability compromises iPSC utility, leading to confounding results and potential safety risks. Genetic alterations accrue as cells are passaged or adapt to changes in their environment, underscoring the importance of maintaining a robust bank of verified iPSCs with regularly validated genetic profiles.

Storage protocols

Like all cells, iPSCs are vulnerable to contamination and notoriously fragile, and inappropriate storage conditions can lead to genomic instability and loss of viability. In addition to maintaining appropriate storage conditions (liquid nitrogen), biobanking infrastructure must provide robust security and contingency systems to ensure cell integrity long term. Expert handling from generation to storage is crucial for maintaining the viability and functionality of iPSCs. Traceability is another vital factor as regulatory bodies require robust audit-ready documentation throughout development and production.

Selecting the right iPSC partner

With so many factors influencing iPSC quality, especially donor diversity and genomic stability, researchers need a provider that they can trust will meet the highest standards.  Sampled is a fully integrated analytical laboratory and biorepository that distributes high-quality iPSC lines for the NINDS, NIMH, SFARI, and EBiSC repositories, and provides robust iPSC generation services to suit any project.

Learn more at sampled.com/gen