Objective
The objective of this proposal is to use advanced bioprinting technology to systematically investigate how the spatial organization and ratio of stem cell-derived alpha, beta, and delta cells influence islet function in vitro. By precisely assembling these endocrine cells into 3D structures that mimic the natural architecture of human islets, we aim to identify design principles that optimize hormone secretion and glucose responsiveness. This work will generate critical insights into the role of islet cytoarchitecture in regulating blood sugar, laying the groundwork for future development of more effective, long-lasting cell-based therapies for Type 1 Diabetes.
Background Rationale
Type 1 Diabetes (T1D) is a disease in which the body’s immune system destroys the insulin-producing cells of the pancreas, called beta cells. Without insulin, the body cannot regulate blood sugar levels, leading to serious health problems. While treatments like insulin injections and glucose monitors help people manage the disease, they do not cure it or restore natural blood sugar control. Many people with T1D continue to face long-term complications and a significant daily burden.
Scientists are working on new therapies that could replace the lost beta cells using stem cells—cells that can be turned into many different cell types, including the hormone-producing cells found in the pancreas. This approach has the potential to restore insulin production and offer a lasting solution to T1D.
However, making beta cells alone may not be enough. In the human pancreas, beta cells don’t work in isolation. They are part of small, highly organized clusters called islets of Langerhans, which also include alpha cells (that produce glucagon) and delta cells (that produce somatostatin). These three cell types work together, using signals to communicate and maintain stable blood sugar levels throughout the day. The specific organization and interaction of these cells are essential for proper function.
Unfortunately, most current lab-grown islet models do not recreate this natural 3D organization. Without that structure, the implanted cells may not work as effectively or may not last as long. To build better therapies, we need to understand how the arrangement of different cell types within an islet affects their ability to regulate blood sugar.
This project addresses that need. Using advanced bioprinting technology, we will build lab-grown models of islets with carefully controlled arrangements of alpha, beta, and delta cells. These 3D-printed tissues will allow us to explore how cell positioning and ratios affect their ability to sense and respond to glucose—without needing to conduct any animal studies at this stage. This foundational knowledge will help guide the design of more effective cell-based therapies for T1D in the future.
By recreating the architecture of real human islets and studying how it impacts function, this project takes a crucial step toward turning promising lab science into real-world treatments that could transform the lives of people with T1D.
Description of Project
Type 1 Diabetes (T1D) is a serious autoimmune disease that affects millions of people worldwide. It occurs when the body’s immune system mistakenly destroys insulin-producing cells in the pancreas, called beta cells. Without insulin, the body cannot regulate blood sugar levels properly, leading to life-threatening complications. Current treatments, like insulin injections and continuous glucose monitors, help manage the disease but do not cure it. People with T1D still face daily challenges, long-term health risks, and reduced quality of life.
Our project is focused on developing a curative therapy for T1D using stem cell technology. We are working to create an implantable “islet-like” structure made from stem cells that can produce insulin and other key hormones needed to regulate blood sugar. This therapy would replace the lost pancreatic function and free patients from the burden of lifelong insulin therapy.
However, simply making insulin-producing cells is not enough. In the human body, insulin is produced by specialized clusters of cells in the pancreas called islets of Langerhans. These islets are organized in a very specific 3D structure, with different cell types (including insulin-secreting beta cells and glucagon-secreting alpha cells) interacting in close proximity. This structure is essential for fine-tuned blood sugar control. When we try to recreate these cells in the lab without maintaining their proper organization, the resulting implants often don’t work as well or last as long.
To overcome this challenge, we are bringing together experts in stem cell biology (Peterson Lab) and bioprinting (Fluicell AB). Fluicell has developed a groundbreaking “bioprinting” platform called Nexocyte™. This platform allows us to precisely place different cell types into custom patterns and architectures, mimicking the natural organization found in human islets. It’s like building a miniature, functional pancreas at the cellular level.
In this project, we will use stem cells to make the three key endocrine cell types found in pancreatic islets: insulin-producing beta cells, glucagon-producing alpha cells, and somatostatin-producing delta cells. We will use Nexocyte bioprinting to organize them into engineered “islet implants” with different spatial arrangements and cell ratios. These implants will be tested in the lab and in diabetic mouse models to determine which designs lead to the best blood sugar control and longest-lasting results.
We believe that by controlling both the composition and the organization of cells in these implants, we can dramatically improve their performance and bring this therapy closer to clinical use. In addition, this technology may help us better understand how islets work and what goes wrong in diseases like T1D.
Anticipated Outcome
This project is designed to improve our understanding of how different hormone-producing cells in the pancreas—specifically alpha, beta, and delta cells—work together to regulate blood sugar. In healthy individuals, these cells are organized into small clusters called islets, where their precise arrangement and interaction are key to stable blood sugar control. In people with Type 1 Diabetes (T1D), these cells are destroyed, and that delicate balance is lost.
Using advanced bioprinting technology, we will create stem cell-derived islet-like structures in the lab that allow us to carefully control how these cell types are arranged in 3D space. This will allow us to study, for the first time in a highly controlled way, how the location, ratio, and interactions of alpha, beta, and delta cells affect hormone release and overall function.
By the end of this project, we expect to achieve the following outcomes:
1. Creation of Engineered Islet Models: We will build multiple 3D configurations of stem cell-derived endocrine cells using precision printing. These models will let us systematically test how changes in cell composition and structure affect their ability to sense and respond to glucose.
2. Insights into Islet Organization: We aim to discover which cellular arrangements best mimic the natural function of human islets. This includes understanding how beta cells (which produce insulin), alpha cells (which produce glucagon), and delta cells (which regulate both) influence each other in real time.
3. Functional Testing of Printed Tissues: These printed islets will be studied in vitro using dynamic hormone assays to measure how well they respond to changing glucose levels and how their behavior changes depending on the structure of the tissue.
4. New Design Principles for Cell Therapies: The findings will serve as a blueprint for building more effective islet replacement therapies in the future. The knowledge we gain will be critical for designing future implants that function more like natural pancreatic tissue.
Ultimately, this project will help us understand how to build islet tissue that works—not just looks—like the real thing. It’s a key step toward better therapies for T1D that are based on how the pancreas actually works, not just on replacing lost cells.
Relevance to T1D
Type 1 Diabetes (T1D) is a chronic autoimmune disease that affects millions of people worldwide. It occurs when the body’s immune system mistakenly destroys the insulin-producing cells in the pancreas, making it impossible to naturally control blood sugar levels. People with T1D must rely on insulin injections or pumps for the rest of their lives and face a daily struggle to keep their blood sugar in a healthy range. Even with modern tools like continuous glucose monitors, many individuals still experience dangerous highs and lows, long-term complications, and reduced quality of life.
This project is focused on developing a stem cell-based therapy that could one day replace the lost function of the pancreas. By creating clusters of lab-grown insulin-producing cells—designed to mimic the structure and function of natural pancreatic islets—we aim to restore the body’s ability to regulate blood sugar on its own.
What makes this project especially innovative is our use of advanced bioprinting technology to arrange these cells in precise 3D structures. Just like the cells in the pancreas, these implants will contain multiple cell types working together to control blood sugar in a balanced way. We believe that replicating this natural organization is key to making the implants function better, last longer, and be more effective for patients.
Ultimately, this work could lead to a new type of therapy that offers freedom from daily insulin and a future where people with T1D live without the constant burden of disease management.