Objective
The primary goal of this research is to improve the effectiveness of stem cell-derived beta cells for treating
diabetes by enhancing their maturity and function. In people with Type 1 diabetes, the body’s immune
system attacks and destroys insulin-producing beta cells in the pancreas. Researchers have turned to stem
cells as a potential source for new beta cells, but these stem cell-derived cells often lack the ability to
produce insulin efficiently, making them less effective for transplantation.
This study aims to test a promising small molecule called “harmine”, which has been shown to improve the
maturation of beta cells in other models. We plan to use harmine to help stem cell-derived beta cells mature
more quickly and function more like natural beta cells. Specifically, we want to see if harmine can help
these cells become better at sensing blood sugar levels, producing insulin in response to glucose, and
supporting overall metabolic function.
By improving the maturation and function of stem cell-derived beta cells, this project could help make stem
cell-based treatments for diabetes more effective and less expensive, and bring us closer to developing
viable, long-lasting therapies for people living with the disease.
Background Rationale
Diabetes is a chronic disease that affects millions of people worldwide, and it happens when the body can
no longer produce enough insulin - a hormone that helps regulate blood sugar levels. In Type 1 diabetes,
the body’s immune system attacks and destroys the insulin-producing beta cells in the pancreas. As a
result, people with Type 1 diabetes must manage their blood sugar levels with insulin injections or pumps,
but these treatments don’t fully replicate the body’s natural insulin response.
One promising approach to treating diabetes is to replace the lost beta cells using stem cell-derived beta
cells. Stem cells can be "trained" in the lab to become stem cell-derived beta cells, which could then be
transplanted into people with diabetes. However, the stem cell-derived beta cells often don’t function as
well as natural beta cells. They can struggle with producing insulin at the right time or in the right amounts,
which limits their effectiveness in treating the disease.
The challenge, then, is to find ways to help these stem cell-derived beta cells mature more effectively and
function more like natural, adult beta cells. One potential solution is a small molecule called “harmine”.
Harmine has shown promise in accelerating and promoting the maturation of human cadaveric beta cells
in lab studies, helping them develop the ability to produce insulin more efficiently. However, we don’t yet
know if or how to harmine might optimize development of stem cell-derived beta cells.
This research aims to test whether harmine can improve the maturity and function of stem cell-derived beta
cells, making them more effective for potential use in treating diabetes. By doing so, we hope to make stem
cell-based therapies for diabetes a more viable and successful treatment option.
Description of Project
Type 1 diabetes is a chronic condition where the immune system attacks and destroys the insulin-producing
beta cells in the pancreas. Without these beta cells, the body cannot properly regulate blood sugar levels,
leading to serious long-term complications. Currently, people with Type 1 diabetes manage their condition
with insulin injections or pumps. While this helps control blood sugar, it does not restore the lost beta cell
function or cure the disease.
One potential solution for people with Type 1 diabetes is islet cell transplantation, where insulin-producing
cells are taken from donor pancreases and transplanted into the patient. However, there are not enough
donor pancreases to meet the growing demand. This makes islet transplantation a limited option for most
patients.
Stem Cell-derived beta cell (SC-derived beta cell) therapy offers a promising solution by providing a
renewable source of functional beta cells that could potentially replace the lost insulin-producing cells in
diabetic patients. These lab-grown beta cells could be used in transplantation to replace the lost insulinproducing
cells in people with Type 1 diabetes. While stem cells can be directed to become beta cells, they
are often immature and don’t function as efficiently as fully developed, natural beta cells.
To address this challenge, we are testing a small molecule called “harmine”, which has shown promise in
helping beta cells mature and function better. In laboratory studies, harmine has been shown to enhance
beta cell maturation and function, and we believe it could accelerate the maturation process of SC-derived
beta cells, making them more similar to the fully mature beta cells found in a healthy pancreas.
By using harmine in our research, we hope to improve the quality and functionality of SC-derived beta cells,
making them a more effective option for transplantation in people with Type 1 diabetes. If successful, our
research could lead to better therapies, potentially reducing the need for insulin injections and improving
the effectiveness of islet cell transplants, offering a more permanent and accessible solution for people
living with Type 1 diabetes.
Anticipated Outcome
The goal of this research is to improve the function of stem cell-derived beta cells so that they can better
mimic the insulin-producing cells in a healthy pancreas. We expect that by using harmine, a small molecule
known to help promote beta cell maturation, the stem cell-derived beta cells will become more functional.
Specifically, we anticipate that harmine will help these cells produce and release insulin more effectively,
especially in response to changes in blood sugar levels.
If successful, our research could provide a significant step forward in making stem cell-based therapies for
diabetes more effective. We expect to see clearer evidence that harmine helps the beta cells mature into
fully functional insulin producers. This could lead to better outcomes for people with Type 1 diabetes, who
currently rely on insulin injections but would benefit from a more natural, long-term solution like beta cell
transplants.
By the end of the project, we hope to have demonstrated that harmine can improve the maturity and
functionality of stem cell-derived beta cells in the lab. This would be an important milestone towards
developing stem cell therapies that could one day offer a more effective and lasting treatment for diabetes,
potentially reducing or even eliminating the need for daily insulin injections for patients.
Relevance to T1D
Type 1 diabetes is a chronic condition in which the immune system mistakenly attacks and destroys the
insulin-producing beta cells in the pancreas. As a result, people with Type 1 diabetes must take insulin
every day to regulate their blood sugar levels. However, this is not a cure, and over time, insulin therapy
can be difficult to manage.
Our research aims to develop a better solution: creating insulin-producing beta cells from stem cells. This
could potentially replace the damaged beta cells in people with Type 1 diabetes, offering a more natural
and long-term treatment. However, stem cell-derived beta cells still face challenges in fully maturing and
functioning like native pancreatic beta cells.
In this project, we are testing a small molecule called “harmine”, which has shown promise in improving the
function of human organ donor-derived beta cells. By using harmine, we aim to accelerate and enhance
the maturation and function of stem cell-derived beta cells, helping them to more closely resemble the
mature insulin-producing cells in a healthy pancreas. The ultimate goal is to create functional beta cells that
can be used in transplants to treat people with Type 1 diabetes, reducing or eliminating their dependence
on insulin therapy.
If our research is successful, it could provide a substantial advance in developing a more effective, more
rapid, and less expensive stem cell development process, and a lasting solution for people living with Type
1 diabetes.