Panel Publishes Expansive Guidance on Pluripotent Stem Cells

Seven working groups, comprising 50 scientists, offer the stem cell R&D community much-needed common ground on the development of pluripotent stem cell therapies

It was just 15 years ago that the first clinical trial of a pluripotent stem cell (PSC) therapy was launched, yet the field already looks dramatically different. New technologies, tools, and models have changed how products are evaluated, while increased investment and optimism are fueling a growing pipeline of more than 100 PSC-derived products, in many cases for diseases with no available treatments.  

Yet the terrain for PSC- and induced pluripotent stem cell therapies (iPSC) remains one of the most difficult fields for companies to navigate. Not only are these products extraordinarily complex compared to small-molecule drugs and even large-molecule drugs like monoclonal antibodies, but they are also expensive and difficult to manufacture.  In addition, manufacturing and testing methods applicable to some PSC and iPSC therapies may not be practical for others. Each individual product has a unique development path to the clinic.  

About three years ago, the International Society for Stem Cell Research (ISSCR) began laying the groundwork for a massive effort to provide much-needed guidance to researchers from both the academic and commercial arenas. They solicited help from nearly 50 subject matter experts across the stem cell spectrum and assigned them to seven working groups based on their expertise. This work led to the publication last October of the “Best Practices for the Development of Pluripotent Stem Cell-Derived Therapies,” a 335-page click-through document intended to help navigate from early product development through licensure. This month, the project team, which includes Shawna Jackman, PhD, DABT, Director of Cell and Gene Therapy at Charles River’s Shrewsbury site, published a companion piece in Stem Cell Reports entitled "Charting the Translational Pathway: ISSCR Best Practices for the Development of PSC-Derived Therapies," highlighting some of the key considerations, practices, and acronyms detailed in the best practices document. ISSCR did an excellent job at creating the infrastructure for this project and bringing together the key experts to effectively pull together these documents to clarify industry standards and promote good science for successful development of stem cell therapies.  

Eureka caught up with Dr. Jackman to learn more about the contents of the report, its significance to the field and what challenges remain.

What does the ISSCR do?

Shawna: The International Society for Stem Cell Research (ISSCR) has always been very focused on standards and providing guidance on how the cells should be used and how this type of research should be conducted. In the early 2000s, they were the first to publish guidance documents on stem cell sourcing, including the ethics surrounding stem cells and what we can do with them. And three years ago, they released the Standards for Human Stem Cell Use, which outline basic core principles for the laboratory use of both tissue and pluripotent human stem cells, as well as the in vitro model systems that rely on them. 

For the Best Practices project, ISSCR identified seven different working groups. What are the focuses of these different working groups? 

Shawna: The seven working groups focused on, first, the generation of iPSC lines, then allogeneic cell banking, raw materials and consumables, regulatory considerations, which I contributed to though I wasn’t a member of, drug substances, and drug products.  Then there was my working group, nonclinical development, and finally clinical trials. You can see that the breakdown of the different groups really highlights where most of the focus in developing these cell products lies: manufacturing and cell characterization.

Before the ISSCR initiated this project, what was the landscape like for cell therapy developers and the labs working on their products? 

Shawna: A lot of guidance we have from the global regulatory bodies need to remain broad enough to be able to allow for the novelties that these cell products bring. Each program will be unique and specific to that particular cell product. But because these products are so different, it can be really hard to gain a clear understanding of all the factors to consider when developing one cell therapy vs. another. For instance, let’s say a cell therapy is being developed for an ocular disease in which all the cells are engrafted into the patient and are intended to l remain there forever. Then let’s say you have another product that is also a cell therapy but is really just being used to treat inflammation on a specific occasion, like a surgical procedure, and only remains in the body for a short period of time. 

The ocular cell therapy developer says they need to conduct a 9-month study with 100 rats to obtain regulatory approval. The developer of the anti-inflammatory drug hears that and thinks they need to do the same study with the same number of animals and duration. But the risks from the two different cell products are completely different because of their intended uses and persistence. This is how recommendations and requirements can become very convoluted for these bespoke therapies, and this is just a small example of why it can be hard to determine which recommendations need to be applied to which products. 

I imagine the technology has really advanced a lot, too?

Shawna: Yes, the tools and capabilities used to make cell therapies have expanded rapidly; the way you might have characterized a cell 15 years ago isn’t even applicable anymore, because the new detection methods and assays we have are so much more sensitive. For instance, one risk of induced pluripotent stem cells is that one of those cells may transform into unintended cell types like tumorigenic cells. This is one of the aspects ofpreclinical risk assessment, evaluating the cells for their potential for tumorigenicity. Years ago, the only option for evaluating tumorigenicity was in vivo experiments. You take the cells, place them in an immunocompromised rodent using the intended route of administration, and evaluate over months and months to see if they form tumors.  We still perform this in vivo evaluation when necessary, but it is now coupled with newer, highly sensitive in vitro methods that are also crucial for de-risking these cell products.

Does the guidance that came out of this effort make the process easier for the research community to navigate? 

Shawna: I think so. By no means was this guidance document ever intended to be the ‘only reference needed but it is intended to have a combination of best practices and what should be considered. At different points in development, stem cell developers are thinking about different things. The steering committee was really clear in the goal of providing a comprehensive document that had to be easy to navigate and easy for users to find the specific information that they needed for the particular question at hand. 

Within the preclinical working group that you were a part of, did everyone have specific roles or research assignments? What did Charles River bring to the table?

Shawna: I was part of a group of eight subject-matter experts from academia, government,  and research consultants. Everyone came with a different perspective. Some members worked on specific disease areas, such as neurological diseases, whereas we, meaning Charles River, actually design and conduct studies on cell therapy products. I was able to provide much of the practical information needed for these kinds of studies, such as how much blood you can collect from a single animal to run different assays. 

What were some of the biggest challenges in finding scientific consensus?

Shawna: One of the biggest was that we were all using different terms. We realized we had to go back to the drawing board, define everything, and decide how we wanted to discuss it moving forward to achieve consensus. Once we took that time to develop consistent terminology and definitions, the conversations moving forward to defining the best practices went very quickly.  We met face-to-face in Edinburgh in 2025 and talked through the journey that each of the working groups encountered in the effort to build comprehensive perspectives. Everybody spent the first couple of months talking about terminology, and before long, we had an entire section turned into a glossary of terms and a list of the reference materials that could be used across the board. The glossary and reference materials turned out to be a kind of information bible that researchers can access, and they are also helpful for regulators. 

This document covered a lot of ground. What challenges remain for the field going forward?

Shawna: The challenges of bringing stem cell therapies to market have not changed; there are still obstacles to overcome with manufacturing, logistics, and high costs.  However, this comprehensive, interactive Best Practices tool is intended to provide a global perspective on the regulatory landscape and outline key principles and decision points to facilitate the development of safe and effective PSC-derived therapies.