The islets of Langerhans, clusters of cells scattered throughout the pancreas, are responsible for producing insulin, a hormone that regulates glucose levels and metabolism. In type-1 diabetes, the body’s own immune system attacks and destroys beta cells, leading to insulin deficiency.
Without insulin, individuals with type-1 diabetes face life-threatening consequences. Current treatments involve insulin injections or pumps, but these are not a cure. Researchers are investigating ways to replace and protect transplanted beta cells from immune rejection, offering hope for a potential cure.
One approach involves modifying laboratory-grown beta cells by disrupting their production of HLA proteins, which the adaptive immune system recognizes as foreign and attacks. This approach, proposed by Sonja Schrepfer of the University of California, San Francisco (UCSF), aims to render the cells invisible to the adaptive immune arm.
However, disrupting HLA protein production can attract the attention of the innate immune system. To address this, Schrepfer’s team overexpressed a protein called CD47, which signals to the innate immune system that the cells are not a threat.
In experiments with laboratory monkeys, Schrepfer’s team successfully reversed diabetes by transplanting modified beta cells. The cells remained undetected by the immune system for over six months. Human trials are currently underway to evaluate the safety and efficacy of this approach.
Another strategy involves engineering suppressor cells to protect beta cells from attack. Suppressor cells can calm down killer T-cells, which are responsible for destroying foreign cells. Researchers at the Technical University of Munich are developing this approach, which does not require disrupting HLA protein expression.
Additionally, scientists are exploring ways to enhance the function of beta cells. Lori Sussel of the University of Colorado has shown that boosting the levels of a protein called MAFA can increase insulin production.
Type-1 diabetes affects a significant number of individuals worldwide. If successful, these research efforts could lead to a cure or improved treatments for the condition, offering hope to millions.
