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Changing mentalities when it comes to stem cell genomic stability testing

Dr. Marcela Garita-Hernandez, Pharm D, PhD, has been working on human Pluripotent Stem Cell (hPSC) lines since 2005. Now Director of the iPS Research Lab at Ocular Genomic Institute (OGI), Department of Ophthalmology at Harvard Medical School, she explains why testing for genomic abnormalities is critical for the future of science.

Stem Genomics (SG): Are there any events or situations that have led you to pay particular attention to genomic abnormalities in your career?
Dr. Garita-Hernandez: When I started working on embryonic stem cells back in 2005, we did not know much about genomic abnormalities of course. The field was learning and has come a long way. During that time, I learned that you need to check your cell lines routinely, as nothing can help you predict genomic abnormalities without testing.
SG: What are your motivations for testing? After all, not all genomic abnormalities will be detrimental to your research work.
Dr. Garita-Hernandez: As we know, genomic abnormalities are frequent in hPSCs. If your raw material is not stable, it is very difficult to trust any differentiation changes down the line. Are they attributed to the differentiation itself or are they a derived cause from a genomic abnormality? To have true confidence in your work, you need to eradicate that latter possibility. And of course, it is critical to ensure that your starting material is compliant with the highest quality standards for the validity of your research project.
SG: We recently attended the ISSCR conference in Boston on the latest ISSCR standards for Human Stem Cell Use in Research and were pleased to see that some clear guidance is now available for more rigor and reproducibility in the field. The ISSCR also made sure that this guidance was technically and financially achievable for all labs. What is your take on this?
Dr. Garita-Hernandez: I was there too and I agree that we now benefit from guidance to help us achieve the highest quality standards. There are also a lot of off-the-shelves solutions (kits and services) readily available these days. Testing is the easy part of our work really! Still I’m surprised to see so few genomic abnormalities reported in published papers. In my experience, genomic abnormalities happen far more often than we would expect, even when your cell lines originate from well-established labs.
SG: That is also a conclusion that was drawn from this conference. A call was issued to be more open about those abnormalities to benefit everyone. Perhaps this will gradually change as new generation of scientists arrive in the field?
Dr. Garita-Hernandez: Training the new generations of scientists to follow the right procedure is critical for the future of our science. In my case, I ensure that my students incorporate genomic stability checks as part of their onboarding program. Basic training includes a full QC of a couple of clones from thawing the vial to chromosomal abnormalities. With all the solutions now available out there, they have no excuses for not testing.

Thank you Dr. Marcela Garita-Hernandez for accepting to share your invaluable experience.

Click here to access the latest ISSCR standards for Human Stem Cell Use in Research

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