Objective
The goal of this research project is to help advance a new type of treatment for people with Type 1 Diabetes (T1D): stem cell–based β cell replacement therapy. In T1D, the body’s own immune system destroys the insulin-producing β cells found in the pancreas. These cells are essential for regulating blood sugar, and without them, people must rely on multiple daily insulin injections or pumps for survival. However, current treatments do not fully replicate the natural blood sugar control that healthy β cells provide.
Stem cell therapy aims to solve this by replacing the lost β cells with new ones created in the lab. Scientists can now generate β-like cells from stem cells, either embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs). iPSCs are created from ordinary adult cells (like skin or blood cells) and reprogrammed to behave like embryonic cells, capable of becoming any cell type in the body, including β cells.
Our project focuses on how to select the best iPSC lines for creating these replacement β cells. Not all iPSC lines are the same, some are better at turning into functional insulin-producing cells than others. We aim to identify the key qualities that make an iPSC line suitable for clinical use. To do this, we will study five pharmaceutical-grade iPSC lines provided by a commercial partner, and assess how well each performs in lab experiments that simulate the cell therapy process.
We will evaluate each line’s ability to become β cells, how safe they are, whether they provoke immune responses, and how functional the final β cells are, both in lab tests and in animal models of diabetes. By the end of the project, we hope to define a clear and science-based method to choose the most promising iPSC lines for future diabetes cell therapies.
Background Rationale
People with Type 1 Diabetes currently depend on lifelong insulin therapy, but even the most advanced forms of insulin delivery cannot match the body’s natural system. Poorly controlled blood sugar leads to long-term complications including nerve damage, kidney failure, blindness, and cardiovascular disease. There is an urgent need for treatments that go beyond insulin replacement and aim for a true cure.
One of the most promising approaches is replacing the destroyed insulin-producing β cells using stem cell–derived cells. This is already being tested in clinical trials, and some early results are very encouraging. However, a major challenge is variability: some stem cell lines work better than others, and we don’t yet fully understand why.
This is especially true for iPSC lines, which can vary in their ability to turn into functional β cells. Because iPSCs are a potential source of personalized or “off-the-shelf” treatments, knowing how to select the best ones is critical. Right now, no standard methods exist for evaluating which iPSC lines are most suitable for β cell therapy, and researchers often rely on trial and error.
This project addresses this gap. By systematically studying high-quality iPSC lines and using advanced tools like genomics and artificial intelligence, we will identify measurable features, called Critical Quality Attributes (CQAs), that predict which lines will perform best. This knowledge will not only improve the efficiency and safety of future stem cell–based therapies for T1D but also help make them more widely available.
Description of Project
Stem cell–derived β cell replacement is an emerging and promising strategy for the treatment of Type 1 Diabetes (T1D). Our project focuses on a specific type of stem cell called induced pluripotent stem cells, or iPSCs. These are adult cells (such as from skin or blood) that have been reprogrammed to return to a stem cell state, meaning they can be turned into any other cell type in the body, including insulin-producing β cells. Unlike embryonic stem cells, iPSCs avoid ethical concerns and can be tailored to match the patient’s immune system, potentially reducing the need for lifelong immunosuppressive drugs.
While recent clinical trials using stem cell–derived β cells have shown promise, some patients have even achieved insulin independence, there are still major challenges. One of the biggest is selecting the right starting iPSC line. Not all iPSCs behave the same way: even when grown under the same conditions, different lines can vary in how well they become β cells, how safe they are, and how suitable they are for large-scale production. Currently, researchers have no standardized way to pick the best lines before starting months of time-consuming lab work.
This project aims to solve that problem by creating a clear, science-based method for selecting the best iPSC lines for β cell therapy. We will start by evaluating five high-quality iPSC lines that have already been manufactured under strict pharmaceutical standards (known as GMP, or Good Manufacturing Practice) by a leading biotech company. These lines have been carefully screened for safety, genetic stability, and compatibility with clinical use.
First, we will study each iPSC line in its early stage, before it starts becoming a β cell. We will use advanced tools like RNA sequencing (to analyse gene expression), deep learning (AI models trained on cell images), and immune profiling (to see how the cells interact with the immune system). This will help us identify “predictive markers”, early signs that a line will perform well in producing functional, safe β cells.
Next, we will guide each iPSC line through a multi-step process to turn it into insulin-producing β cells. We will evaluate how well each line performs by checking key features: the percentage of β cells produced their ability to release insulin when exposed to glucose, their genetic stability, their safety in animal models, and their response to immune cells. We will also assess whether the manufacturing process is consistent and scalable.
Finally, we will combine all this information into a selection framework, identifying which iPSC lines are best suited for β cell therapy. This framework will be aligned with the standards of regulators like the FDA ad EMA, making it easier to move toward human trials.
In the future, this work could dramatically speed up the development of stem cell–based treatments for T1D. It will also help researchers worldwide choose the right iPSC lines with confidence, reducing trial-and-error, costs, and time. While our initial focus is on “off-the-shelf” therapies using donor cells, the tools we develop will also support future personalized treatments using a patient’s own cells, potentially without the need for immune suppression.
Ultimately, this project brings us closer to a long-term goal: a safe, effective, and possibly curative therapy for people living with Type 1 Diabetes.
Anticipated Outcome
At the end of this two-year research project, we expect to deliver a clear, science-based method for identifying the best iPSC lines to use in β cell replacement therapy for T1D.
We will produce a detailed evaluation of five high-quality iPSC lines. For each, we will document their strengths and weaknesses in terms of their ability to turn into insulin-producing β cells, how well they function in lab and animal tests, and how visible or invisible they are to the immune system. This work will allow us to identify which features of iPSC lines, like specific genes or cell shape, are linked to better outcomes.
A major goal is to define a set of “Critical Quality Attributes” (CQAs). These are measurable indicators that predict whether a stem cell line will succeed in producing safe and effective β cells. Once these CQAs are established, they can be used by scientists and biotech companies to choose or design better cell lines for future therapies.
Importantly, this work also helps set the stage for moving these treatments into human trials. By using Good Manufacturing Practice (GMP)-grade iPSC lines, we are aligning our research with the standards required by regulators for clinical use. We also include studies of immune compatibility, to better understand how the patient’s immune system might respond to the transplanted cells.
Overall, our results will help accelerate the path toward more reliable, effective, and safe β cell replacement therapies for people living with Type 1 Diabetes.
Relevance to T1D
This project is directly focused on improving future treatment options for people with Type 1 Diabetes (T1D). It supports the development of a potential cure: cell-based therapy that restores insulin production by replacing the lost β cells in the pancreas.
While insulin therapy remains essential, it does not cure the disease or eliminate its complications. Stem cell–derived β cell replacement offers a promising alternative by potentially restoring natural blood sugar control. However, for this therapy to succeed and become widely available, we must first solve a major technical problem, how to reliably produce high-quality β cells from stem cells.
Our project contributes to this goal by creating a new framework for selecting the best iPSC lines for β cell therapy. This will improve both the safety and effectiveness of future treatments and reduce the time and cost of developing new products. The use of GMP-compliant cell lines and a standardized evaluation process ensures that our findings are immediately relevant to clinical translation.
In the long term, the tools and knowledge generated by this research will also be useful for developing personalized (autologous) cell therapies, which could eliminate the need for immunosuppression altogether. For the millions of people living with T1D, this work brings us a step closer to a world where insulin injections are no longer necessary.