Earlier this year, the UK Stem Cell Bank validated the first European Union of Tissue and Cell Directives (EUTCD)-compliant human embryonic stem cell (hESC) lines: the MasterShef hESC lines 2, 7, and 10 Derived at the University of Sheffield Center for Stem Cell Biology, these clinical-grade hESC lines are a major breakthrough for researchers requiring high-quality starting material for cell products intended for clinical, bringing stem cell implementation in medical therapies overall a significant step closer to realization.

Recently, Biological Industries had the pleasure to speak with Dr. Zoe Hewitt, project leader for the derivation and validation of the MasterShef hESC lines.  Dr. Hewitt walked us through the fascinating story of this pioneering work, as well as some of the bottlenecks, challenges, and success stories from her lab as they strived to translate hESCs from the bench to the clinic.

We asked Dr. Hewitt what she considers to be the critical element in ensuring cell quality in her labs.  “It’s reliability, isn’t it? And reproducibility. [It’s whether] you’ve got confidence in your culture system.” she said.  “Embryonic stem cells are the most challenging cell type to work with because they are unpredictable. So, if you’ve got anything that makes that predictability more reliable, then you have a fighting chance of getting where you want to be, really.”

In order to minimize variability in the system and aid with GMP compliance, the new clinical-grade MasterShef hESC lines were derived using NutriStem® hPSC Medium, a defined, xeno-free, GMP stem cell medium.

“The nice thing about NutriStem hPSC Medium is that it wasn’t developed with a specific matrix,” giving the lab the freedom and versatility to derive and culture new lines on a variety of substrates.  So far, the MasterShef lines are used with NutriStem on human feeders, CELLstart™, laminin-511, and laminin-521 matrices.

“The other thing we really liked about [NutriStem] was that it was a complete media when it came in, so you eliminate the possibility of someone making it incorrectly.”  She also mentions that, while mixing components to make a complete media is generally a quick process, “it’s open to error – human error.”

NutriStem hPSC Medium was easily incorporated into the good manufacturing processes and procedures of her GMP-compliant lab.  Dr. Hewitt explains that even the simple act making the media itself can have a significant impact.  “So you say, ‘Yeah, we’ll make this bottle of media’, which is a 2 minute job, but it’s a 7 or 8 minute job if you’ve got to fill in all the paperwork and the traceability that’s involved in that.”

Dr. Hewitt’s lab also found it helpful to be able to reserve large quantities of a single batch of NutriStem, meaning that “we can remove variation from our process, which in the clean room was gold, really.” Because the NutriStem hPSC Medium can be thawed and re-frozen in smaller quantities, “we’ve been able to practically eliminate waste of media.”  Using single aliquots of the media at a time was particularly useful to the lab. ”We don’t throw media away anymore.”

When looking for a new media to derive and culture cells in their clean room, it was important that the media be regulatory-compliant.  Her team worked through the challenges of transferring research protocols to a clean room setting.  Essentially, the quality systems and regulation required to maintain a GMP lab was “a completely new culture for stem cell biologists to consider working in.  Up until that point, we didn’t really know what GMP was. We didn’t have a good appreciation for the level of paperwork and extra time it took to do everything, and the impact that that had on what we were trying to achieve.”

But are clinical-grade cells and media just for labs doing clinical studies?  Dr. Hewitt thinks not, and argues that time and effort can be saved by starting with clinically-compliant materials for all research with the downstream goal of clinical use.  This is especially important with finicky hESCs, since they are all unique, and as Dr. Hewitt states, they all behave slightly differently.

“In order to get a cell product to the end (clinic), you need to start with material that you know is going to go from start to end,” she explained. The risk being taken when switching from research-grade cells, media, or other materials to a clinical-grade version is clear.  “To do a lot of research on the research-grade ES cells and then move to the clinical-grade version, it could be that the protocol that you just spent 10 years developing didn’t work.”

To learn more about how Dr. Hewitt’s experience setting up protocols and quality systems to generate new hESC lines acceptable for clinical use, watch the full interview here.

 

About Dr. Zoe Hewitt:

Dr. Hewitt first learned about hESC after arriving early for a field trip at University of Darby. After reading Jamie Thomson’s publication on hESC derivation, she was fascinated by these cells and the potential they held for regenerative medicine. She pursued a PhD at the Roslin Institute at the University of Edinburgh, after which she joined the lab of Prof. Harry Moore at the University of Sheffield, with the mission to set up the clean room facilities and design the quality management system to derive hESC. She is now a project manager for the UK Regenerative Medicine Platform, a translational alliance between the University of Sheffield, University of Loughborough, University of Cambridge and the UK Stem Cell Bank, investigating the bottlenecks in translating stem cells from bench to the clinic.

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We would like to warmly thank Jean Emly at Geneflow, BI’s local UK distributor, for her continuous collaboration and long-lasting partnership. 

 

CORRECTION OCT 16, 2017: Earlier versions of this post incorrectly associated Dr. Zoe Hewitt’s work at the University of Sheffield with that of the UK Stem Cell Bank. This version has been corrected with the correct affiliation of each party. BI apologizes for any confusion to the involved parties.