Stem cell research holds tremendous promise for the future of medicine, but successful therapies will require strong, evidence-based research that is conducted with scientific integrity. To support researchers in this pursuit, the International Society for Stem Cell Research (ISSCR) has developed standards that “identify quality standards and outline basic core principles for the laboratory use of both tissue and pluripotent human stem cells and the in vitro model systems” called the Standards for Human Stem Cell Use in Research.
These standards were developed through collaboration with researchers across the globe. Among those leading the charge were Stem Cell Regenerative Medicine Center (SCRMC) members Tenneille Ludwig, PhD, a senior scientist and director of the WiCell Stem Cell Bank, and Anita Bhattacharyya, PhD, an associate professor of Cell and Regenerative Biology at the University of Wisconsin–Madison.
“We’ve had a lot of conversations within the community as a whole about the need for increased rigor and reproducibility in science in general,” says Ludwig. For stem cell research specifically, Ludwig states, “We have data that we’ve generated that shows that 30 to 35 percent of everything we are receiving (at the WiCell Stem Cell Bank) from academic researchers for distribution has some sort of fatal flaw that will significantly impact the quality of data obtained from using it in research. And that’s particularly alarming when you think about the fact that the material that people send us is what they consider their very best material.”
Ludwig noted that the National Institutes of Health (NIH) has also become aware of the need for increased rigor and reproducibility and is now requiring all grant applications include a section on rigor and reproducibility.
“To find that 35 percent of the submitted stem cell lines are not of the appropriate quality to be getting any sort of reliable data creates big issues for any conclusions and it creates an issue for the scientific journals as well. How do they know what is being published is reliable?” says Ludwig. “It doesn’t matter how good the quality of your science is if the underlying materials are compromised. The ISSCR recognized this was an ongoing issue within the field and put together working groups to develop standards that are designed to increase the quality of science that we do as a global community.”
When the opportunity came to officially develop the standards, Ludwig jumped at the chance to be involved.
“When asked if I would be willing to co-lead the initiative (with Dr. Peter Andrews from Sheffield University) it made sense given that my whole life’s work is about improving quality, working towards consensus standards and identifying best practice,” Ludwig said.
Together, they worked to select a steering committee that would drive the standards forward.
“We were very careful to select individuals from literally all over the globe,” Ludwig says. “We wanted a gender balance, a regional balance, and leading experts in the field. So, to say that there are only four representatives from the US on the Standards Task Force and two of them are here at the University of Wisconsin is pretty exciting,” Ludwig said of herself and Bhattacharyya, PhD, who was recruited to serve on a specific portion of the standards for disease modeling.
“Anita [Bhattacharyya] was on the working group for developing disease model systems thanks to her strong background working in Down Syndrome models. She was really one of the only experts we had who looks specifically at cellular models of disease as opposed to organoids and gene editing, so it was fabulous to have her contribution,” says Ludwig.
Bhattacharyya was thrilled to join the team as she has been keeping up to date on ISSCR initiatives and activities for more than 10 years.
“ISSCR has really provided me with resources and the information I needed not just as a researcher, but also as the chair of the stem cell research oversight committee and a working group for intellectual and developmental disorder research centers across the country” says Bhattacharyya. “I, like many people, felt that the ethical policies that were sent out in the last iteration of the ISSCR Guidelines were helpful, but we really needed to think more about the practical issues of working with human stem cells, it’s not like working with other cells. You need to have some understanding of the provenance of them and what additional ethical considerations come along with the research.”
With this in mind, Bhattacharyya, Ludwig, and the entire team began working on appropriate standards that could be adopted by labs of any size and budget.
“I was really impressed by the level of discussion and that people didn’t always agree on what we wanted to set forth but worked well together to come to a conclusion,” says Bhattacharyya. “We were constantly talking about how to set the bar and what is reasonable, while trying not to be too prescriptive.”
Ludwig agreed, adding, “We worked very hard to get into a consensus driven decision when we met with each working group. Certainly, there were a lot of opinions when you get that number of high-profile investigators together. You must find a way to come to consensus and compromise. And it was a really great team to work with because everyone was motivated to do that. There was an atmosphere of mutual respect that allowed open discussion and a common desire to understand different perspectives. Everyone was motivated to work together and make a difference.”
After several months of collaboration, the standards have now been released on the ISSCR website. The team is pleased to see their work come to fruition and they’ve received positive feedback, with Ludwig and Andrews receiving the 2024 ISSCR Public Service Award. They’ve also received some comments that the guidelines have set the bar high.
“Since it’s come out, I have received feedback from researchers who feel that it’s a lot to do, it’s going to cost more, and I completely agree because I have my own research lab and I understand that. But I think that the standards are important for us for to be able to move the stem cell field forward with rigor and reproducibility,” says Bhattacharyya.
The ISSCR is also proud to release this document and honored to have the involvement of researchers like Ludwig and Bhattacharyya.
“The call for rigor and reproducibility in scientific research, and specifically stem cell research, has been growing. The importance of it has been raised by journal editors, effects of its absence have been documented in the literature, and the financial impact has been highlighted by funders,” says Jack Mosher, PhD, a scientific advisor with ISSCR. “To address this problem, the ISSCR, in partnership with global stakeholders, developed the Standards for Human Stem Cell Use in Research. With significant contributions from UW scientists, Tenneille Ludwig, who co-chaired the project, and Anita Bhattacharyya, the document provides a set of best practices and reporting recommendations for pluripotent and tissue stem cell research for scientists worldwide.”