Researchers convert human stem cells into insulin-producing beta cells. Could this be the answer to personalized treatment or even a cure for type 1 diabetes?
2021 marks 100 years since the discovery of insulin. This lifesaving treatment changed type 1 diabetes from a terminal disease to a treatable disease. Even 100 years on, insulin remains the only effective treatment for people with type 1 diabetes, but the search is still on to find a cure. In this article, we summarise a recent study where researchers were able to transform stem cells into insulin-producing pancreatic cells, bringing us one step closer to finding that cure.
What is type 1 diabetes?
Type 1 diabetes is an autoimmune disease where a person’s own immune system attacks and destroys the beta cells of the pancreas. These beta cells are responsible for producing insulin, an essential hormone to control sugar levels in the blood. People affected by type 1 diabetes are unable to make any insulin and are completely reliant on insulin injections for controlling their blood sugar levels.
Insulin treatment of type 1 diabetes
Automated insulin delivery systems and minimally invasive blood sugar monitoring devices have simplified the treatment and control of type 1 diabetes. Yet, type 1 diabetics must still follow a carefully controlled lifestyle and diet, and their life expectancy is 12 years less than those without the disease. So it is still important to find a way to restore beta cell function itself within the body, so the body can produce its own insulin in response to blood sugar levels.
Lab production of beta cells
Stem cells are the top candidate for cell therapies of type 1 diabetes. They can grow almost indefinitely and can be converted into a whole range of different types of cells in the body given the correct signal. However, determining what those signals are to convert a stem cell to a beta cell has been a challenge.
Many research studies have investigated the use of growth factors to produce beta cells. However, growth factors are expensive and unstable, meaning they are likely to be too costly and inefficient for large-scale use making the product non-affordable.
Are there effective and affordable ways to convert stem cells to beta cells?
Here is where the current study comes in. These researchers stimulated the stem cells with a cocktail of small molecules, rather than expensive growth factors. According to the lead author of the study “[the] small molecules are much cheaper and far more stable than growth factors, and [they] still emulate the effect of growth factors..”
The cocktail of small molecules included a chemical compound the lab designated as CHIR99021 (CHIR), which activated a signaling pathway in the stem cells that directed them to differentiate into other cell types.
But the levels of this CHIR molecule are very important. Higher doses of CHIR converted the stem cells into mature heart cells, not the beta cells they were aiming for. However, they discovered that an intermediate CHIR dose partially activated this pathway, and the stem cells were transformed into a cell that could be coaxed into becoming a mature pancreatic beta cell.
After finally generating mature beta cells in the lab, the researchers then tested their functionality. They found that the lab-derived beta cells can sense sugar levels in the environment and, in response, they produced insulin. Exactly the beta cell function that they were aiming for.
The next challenge is to find an effective way to deliver these lab-made beta cells to patients in a way that the patients’ immune system will not destroy these cells. Once this can be done, they will move on to clinical trials for testing their effectiveness.
Although it may still be years before these chemically coaxed beta-cells can be transplanted into patients to cure diabetes, it is an exciting discovery that is bringing us one step closer to an affordable way to cure type 1 diabetes.
Jiang et al., Generation of pancreatic progenitors from human pluripotent stem cells by small molecules, Stem Cell Reports (2021), https://doi.org/10.1016/j.stemcr.2021.07.021