Posted on 8 March 2022
Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.
Why is this research important: Diabetes mellitus affects millions of people worldwide. It is a condition in which levels of glucose (sugar) in the blood become too high. In type 1 diabetes mellitus, this happens because the pancreas does not produce enough insulin, the hormone responsible for lowering blood sugar. Insulin is produced by cells called beta cells, which come under attack from the body’s own immune system in type 1 diabetes. It is possible to transplant the beta cells from a deceased donor to the pancreas of a diabetic patient, which can significantly improve their quality of life. However, this is rarely done, in large part because of a shortage of donors.
Human pluripotent stem cells (hPSCs) are capable of differentiating (developing) into a variety of specialised cell types. Scientists have learnt how to guide their differentiation, resulting in the production of pancreatic beta-like cells which could be transplanted into diabetic patients. Ideally, hPSCs would be differentiated into pancreatic progenitor cells (PPs), which are only a few steps away from becoming beta-like cells. Those progenitor cells would then be made to divide, producing a large number of cells that could be maintained and differentiated into beta-like cells relatively quickly. Unfortunately, scientists don’t really understand how pancreatic progenitors renew themselves. This means that every time beta-like cells need to be produced, they must be differentiated step by step from hPSCs into beta-like cells. This is a very labour-intensive, time consuming process, making it impractical for treating diabetes at a large scale.
What did the researchers do: In this study, researchers took hPSCs and differentiated them into pancreatic progenitor cells (PPs), which are only a few steps away from becoming beta-like cells. They then attempted make those cells proliferate. To do this, they screened cells for small molecules that could promote the expression of PDX1 and NKX6, two genetic regulators thought to be involved in the expansion of pancreatic progenitor cells.
Key takeaway(s) from this research: The researchers identified a small molecule called I-BET151 that was able to increase the expression of key genes for the expansion of pancreatic progenitor cells. They developed and refined a procedure to expand progenitor cells using I-BET151, and showed that those cells could then be differentiated into beta-like cells. They also showed that transplanting these cells into diabetic mice led to significantly improved blood sugar control.
This study brings us one step closer to a long hoped-for limitless supply of pancreatic beta cells. This would not only solve the supply issues when it comes to beta cell transplantation, but might also avoid the need for recipients to take immune suppressing drugs, as beta cells could be generated from the patients’ own cells, and so would not risk rejection by the immune system.
Human expandable pancreatic progenitor–derived β cells ameliorate diabetes: https://doi.org/10.1126/sciadv.abk1826