Objective
The primary objective of this project is to develop a reliable, large-scale, and clinically compliant process to produce insulin-producing cells from stem cells in order to create a practical and potentially curative treatment for people living with Type 1 Diabetes (T1D). These insulin-producing cells will be made from induced pluripotent stem cells (iPSCs), a special type of cell that can be generated from a patient’s own skin or blood cells and reprogrammed to become any cell type in the body. In this case, the goal is to turn them into pancreatic beta cells, the very cells that are lost in people with T1D.
To make this vision a reality, the research team is working on an advanced and integrated system that can manufacture these cells in a way that is safe, reproducible, and scalable. This means creating a process that can work not just in a research lab, but also in a clinical setting, meeting the high standards needed for medical treatments. The objective is not only to create high-quality insulin-producing cells but also to build a process that can be repeated reliably for many patients, at a reasonable cost, and in compliance with regulatory requirements such as Good Manufacturing Practices (GMP).
The project is broken into three main goals. The first is to create large quantities of stem cells using high-tech, 3D bioreactor systems. These systems allow cells to grow in conditions that more closely resemble how they grow in the human body and are designed to produce billions of healthy cells in a controlled and efficient manner. This stage is often referred to as the “seed train,” and it lays the foundation for all future steps.
The second goal is to convert those expanded stem cells into insulin-producing cells using a carefully designed, step-by-step process that mimics how the pancreas develops in the human body. This process, known as differentiation, must be done in a way that is both scientifically precise and scalable so that large batches of insulin-producing cells can be made consistently. The researchers are adapting and optimizing this process to work in 3D bioreactors, which makes it much easier to scale up for widespread clinical use.
The third and final goal is to develop a way to freeze, store, and transport these insulin-producing cells without damaging them. This process, called cryopreservation, is critical for creating a “ready-to-use” cell therapy product. It allows the cells to be manufactured in centralized facilities, tested for safety and effectiveness, and then shipped to hospitals and clinics when needed. This also ensures that each patient receives high-quality cells, regardless of where they live.
Together, these three goals support the broader objective: to create an off-the-shelf, cell-based treatment for T1D that is practical for real-world use. By focusing on safety, consistency, scalability, and cost-effectiveness, this project lays the groundwork for clinical trials and, ultimately, commercial distribution of a stem cell–derived insulin therapy. If successful, it could reduce or even eliminate the need for insulin injections and transform the lives of people living with T1D.
In summary, the objective of this project is not just to prove that iPSC-derived insulin-producing cells can be made, it’s to develop a complete system that makes it possible to deliver these cells to patients safely, efficiently, and on a global scale. This is a critical step toward achieving a functional cure for T1D and opens the door to using similar technologies for other diseases in the future.
Background Rationale
Type 1 Diabetes (T1D) is a serious lifelong disease that affects millions of people around the world. It occurs when the body’s immune system mistakenly attacks and destroys the cells in the pancreas that produce insulin, a hormone essential for controlling blood sugar levels. Without insulin, the body cannot properly regulate glucose, leading to high blood sugar levels that, over time, can damage organs such as the eyes, kidneys, heart, and nerves. People with T1D must manage their condition by carefully monitoring their blood sugar and taking insulin through injections or pumps for the rest of their lives. Even with modern technology, many patients still face risks like dangerously low blood sugar (hypoglycemia) and long-term complications that reduce their quality of life.
Currently, one of the few ways to potentially cure T1D is through a transplant of insulin-producing cells, known as islet cells, from a deceased donor. These transplanted cells can restore the body’s ability to produce insulin naturally. However, this method has major drawbacks. Donor islet cells are in short supply, and patients who receive them must take powerful medications for life to stop their immune system from rejecting the transplant. These limitations have led scientists to search for better, more sustainable solutions.
One of the most promising breakthroughs in recent years is the development of insulin-producing cells from a type of stem cell called induced pluripotent stem cells (iPSCs). These cells can be made in the lab from adult skin or blood cells and reprogrammed to become almost any cell type in the body, including the insulin-producing beta cells found in the pancreas. Because iPSCs can be created in large numbers and tailored to patient needs, they offer a potentially limitless and more flexible source of therapeutic cells.
However, there are still challenges in turning this exciting idea into a practical treatment. First, current lab methods to grow and convert iPSCs into insulin-producing cells are often slow, inefficient, and not scalable for widespread use. These processes usually happen in flat culture dishes and require a lot of labor and time, making it difficult to produce enough cells for many patients. Second, once the cells are made, there is no reliable method yet to freeze, store, and transport them without losing their effectiveness. Without good freezing techniques, it becomes hard to create a centralized manufacturing system that can supply treatment centers worldwide.
This project was created to solve these problems and move iPSC-based therapies for T1D closer to clinic. The research team is developing a complete, end-to-end system for producing iPSC-derived insulin-producing cells in large quantities, using bioreactors—specialized machines that support cell growth in three dimensions. These bioreactors can grow stem cells efficiently and consistently than traditional lab methods. The team will optimize the process that transforms these stem cells into insulin-producing cells, ensuring high yield and reliable functionality.
To make the therapy practical and accessible, they will also develop a cryopreservation method that allows the cells to be frozen, stored, and shipped without losing their ability to produce insulin. These frozen cells can be delivered to clinics and hospitals, ready for use when needed. This approach not only supports large-scale production and distribution but also makes it easier to test and release batches that meet strict safety and quality standards.
In summary, the rationale for this work is simple yet powerful: current treatments for T1D are not enough, and iPSC technology has the potential to provide a real, lasting solution. By overcoming key manufacturing and delivery challenges, this research could unlock a new era of personalized, stem cell–based therapies that provide lasting insulin independence for people with T1D.
Description of Project
Type 1 Diabetes (T1D) is a lifelong condition in which the body’s immune system mistakenly destroys the cells in the pancreas that produce insulin, a hormone that helps regulate blood sugar. People with T1D must monitor their blood sugar levels constantly and take insulin regularly, often through injections or pumps, to stay alive. Despite improvements in technology, managing T1D is still difficult, and many patients experience serious complications, including dangerously low blood sugar, long-term organ damage, and reduced quality of life.
One potential cure for T1D is to replace the lost insulin-producing cells in the body. This has been attempted through islet cell transplants from organ donors, which can restore insulin production. However, this approach is limited because there are not enough donor organs, and patients often need to take medications to prevent their immune system from rejecting the transplant. To solve these problems, scientists have turned to a promising alternative: creating insulin-producing cells in the lab using a type of stem cell known as an induced pluripotent stem cell (iPSC). iPSCs are special because they can be made from a person’s own cells and can be turned into almost any cell type in the body, including insulin-producing cells.
This project focuses on developing a complete system to manufacture these iPSC-derived insulin-producing cells in large amounts, for clinical use meeting safety and quality standards. The ultimate goal is to create a safe, effective, and widely available treatment that could potentially cure T1D without relying on donor tissue.
The research team plans to achieve this by developing three major components. First, we will grow large quantities of stem cells using advanced equipment called bioreactors that provide the ideal environment for cells to grow in 3D like inside the human body. This process, called the "seed train," ensures that there are enough healthy, high-quality cells to start making insulin-producing cells. Second, the team will guide these stem cells through a carefully designed process to become insulin-producing cells. This involves exposing the cells to specific signals that mimic how the pancreas develops in the body. The researchers will adapt this process to work efficiently in the bioreactors, allowing them to produce millions or even billions of cells per batch. These lab-grown cells will be tested to ensure they release insulin when exposed to sugar, just like healthy pancreatic cells.
The third part of the project involves developing a method to freeze and store the cells without damaging them. This is crucial because it allows the cells to be produced in centralized facilities, stored for long periods, and shipped to hospitals and clinics around the world. The researchers will test different freezing techniques and protective solutions to make sure the cells survive the freezing and thawing process and still function correctly.
To confirm that the cells work as intended, they will be tested in diabetic mice. We will look to see if the lab-grown cells can restore normal blood sugar levels and function like real pancreatic cells after being implanted. In the future, the team also plans to use special gene-editing techniques to make the cells less likely to be rejected by the immune system, which could eliminate the need for patients to take immune-suppressing drugs.
This project is being conducted by experts at the Cedars-Sinai Biomanufacturing Center, in collaboration with a biotechnology company specializing in scalable cell growth systems. If successful, it could revolutionize the treatment of T1D, offering a long-term or permanent solution to millions of people worldwide. The same technology could also be adapted for other diseases where cell replacement is needed, helping to advance the entire field of regenerative medicine.
Anticipated Outcome
The anticipated outcome of this project is the successful development of a complete, large-scale, and clinically compliant system for producing insulin-producing cells from human induced pluripotent stem cells (iPSCs), ultimately enabling a practical and curative therapy for people with Type 1 Diabetes (T1D). This outcome would represent a major scientific and medical breakthrough, offering hope to millions of individuals living with T1D who currently rely on daily insulin injections and face ongoing health risks due to the limitations of existing treatments.
At the heart of this project is the goal of making iPSC-derived insulin-producing cells that are not only functionally effective but also safe, consistent, and easy to manufacture, store, and distribute. By achieving this, the research team expects to produce a cryopreserved (frozen and stored) cell product that can be delivered “off the shelf” to patients in clinics or hospitals when needed. These cells will be grown in specialized bioreactors that support large-scale cell expansion and controlled differentiation, allowing for high volumes of therapeutic cells to be created from just a small starting sample.
The process will include creating a high-densitybank of stem cells, guiding those cells through a carefully developed step-by-step method to become insulin-producing beta cells, and then preserving them through advanced freezing techniques that maintain cell quality and function. The result will be batches of insulin-producing cells that can be stored long-term and retain their ability to regulate blood sugar levels after injection into humans.
Functionally, the cells produced are expected to behave like natural pancreatic beta cells. That means they will sense changes in blood sugar and release insulin in response, helping to maintain stable glucose levels in the body. In laboratory testing, including in diabetic animal models, these cells should restore normal blood sugar control, demonstrating their effectiveness before moving into human trials. If the treatment performs as anticipated, it could dramatically reduce or even eliminate the need for insulin therapy in T1D patients.
An equally important anticipated outcome is that the entire process will be scalable, affordable, and ready for regulatory approval. Many promising stem cell therapies remain stuck in the lab because they cannot be produced at the scale and quality required for widespread use. This project is designed to overcome that barrier by using Good Manufacturing Practice (GMP) standards and incorporating quality controls and cost modeling at every step. That means the therapy could eventually be produced in centralized facilities and shipped globally, helping to make stem cell treatments more accessible to patients across diverse healthcare settings.
Another exciting expected outcome is the development of immune-evasive versions of these therapeutic cells. Using advanced gene-editing techniques, the team is modifying some of the stem cell lines to reduce the risk that the patient’s immune system will attack the transplanted cells. This could eliminate the need for lifelong immunosuppressive drugs, which are commonly required in traditional organ or islet transplants but come with serious side effects. These next-generation “hypoimmune” cells could lead to truly universal donor cell therapies meaning they can be used in any patient without immune matching.
If successful, this project will not only change the treatment landscape for T1D but also establish a model that can be applied to other diseases that may benefit from regenerative medicine, such as Type 2 diabetes, liver disease, or neurological conditions. The knowledge, tools, and technologies developed through this work will help advance the entire field of stem cell-based therapies and bring science closer to real, accessible cures for chronic conditions. Ultimately, the anticipated outcome is a new, life-changing therapy for T1D that is safe, scalable, and within reach for patients around the world.
Relevance to T1D
This project is directly relevant to Type 1 Diabetes (T1D) because it addresses one of the most urgent and long-standing challenges in the treatment of the disease: the permanent loss of insulin-producing beta cells in the pancreas. In T1D, the immune system mistakenly attacks and destroys these beta cells, which are responsible for producing insulin, a hormone that helps the body regulate blood sugar levels. Without insulin, people with T1D must rely on lifelong insulin therapy, typically in the form of daily injections or insulin pumps. Even with modern technology such as continuous glucose monitors and smart insulin delivery systems, people living with T1D still experience serious health risks, including low blood sugar episodes (hypoglycemia), long-term complications affecting the eyes, kidneys, nerves, and heart, and a reduced overall quality of life.
While insulin therapy helps manage the disease, it does not address the root problem: the absence of functional beta cells. One potential solution has been to replace the lost beta cells with healthy ones through islet transplantation from deceased donors. However, this option is limited by a shortage of donor tissue, the need for powerful drugs to suppress the immune system, and variable success rates. As a result, islet transplantation is available to only a small number of patients and is not considered a widely accessible cure.
This is where the current project becomes highly relevant. Researchers are working on creating insulin-producing cells from a special kind of stem cell called induced pluripotent stem cells (iPSCs). These iPSCs can be made from a person’s own skin or blood cells and have the ability to become any type of cell in the body, including the insulin-producing beta cells destroyed in T1D. By developing a reliable and large-scale process to grow and convert these stem cells into functional beta cells, this project aims to provide a sustainable and potentially curative therapy for T1D that does not depend on donor availability.
The research is focused on building a complete manufacturing system that can safely and consistently produce iPSC-derived beta cells in large quantities. These cells will be grown in bioreactors, special containers that simulate the body’s natural environment, allowing the cells to expand and mature efficiently. Once they are fully developed, the cells will be frozen using specialized techniques that preserve their viability and ability to function after thawing. This makes it possible to create an “off-the-shelf” therapy that can be produced in advance, stored, and delivered to patients when needed, much like conventional medicines.
The project also includes efforts to make these cells more compatible with the human immune system. Using advanced gene-editing tools, the team is creating “hypoimmune” versions of the cells that are less likely to be attacked by the patient’s immune system. This could eliminate or reduce the need for immunosuppressive drugs, making the therapy safer and more accessible to a broader group of patients, including children and those with immune sensitivities.
In summary, the relevance of this project to T1D is profound. It directly tackles the fundamental problem of beta cell loss and aims to replace those cells with lab-grown, functional alternatives. The approach is designed to be safe, scalable, and practical for clinical use, offering the possibility of a long-term or even permanent solution to insulin dependence. If successful, this work could transform how T1D is treated, shifting from lifelong management to true disease reversal. It holds the potential to improve the lives of millions of people affected by T1D and pave the way for future breakthroughs in regenerative medicine.