Mitochondria and Energy Metabolism
Islet Cell Biology and Transplantation
Islet cell biology focuses on the study of pancreatic islets, clusters of endocrine cells, primarily beta cells, that regulate blood glucose by secreting insulin. In type 1 diabetes, the immune system mistakenly destroys these insulin-producing cells, leading to chronic hyperglycemia.
Understanding the intricate biology of islet cells, especially the insulin-producing beta cells, is essential for developing effective therapies for diabetes. Insights into their development, function, and interaction with their microenvironment provide the foundation for designing therapeutic strategies.
Building on this knowledge, islet transplantation emerges as a powerful approach to restore lost endocrine function in patients with type 1 diabetes. By transplanting functional islets from donors or stem cell-derived sources into patients, researchers aim to reestablish natural glucose regulation and reduce or eliminate the need for insulin injections.
Research challenges
Current challenges include :
- Islet survival post-transplant. After transplantation, a large proportion of islets are lost within hours due to immediate inflammatory responses and inadequate oxygen and nutrient supply, which compromise their viability and function.
- Immune rejection. The recipient's immune system often recognises the transplanted islets as foreign and mounts an immune attack, necessitating lifelong immunosuppression or the development of immune-evasive strategies.
- Limited donor availability. The scarcity of suitable organ donors significantly restricts the number of islet transplants that can be performed, making it essential to find alternative cell sources such as stem cell-derived islets.
- The need for long-term graft function. Even when initial transplantation is successful, maintaining stable and functional islet grafts over time remains a challenge due to gradual immune-mediated damage, fibrosis, or loss of vascular support.
Local research efforts at the Geneva Diabetes Centre
The Geneva Centre for Diabetes is a leader in diabetes research, with a strong focus on exploring islet biology and advancing islet transplantation as a curative approach. They are actively engaged in research focused on:
- Unlocking pancreatic plasticity: Using human islets and transgenic mice, researchers discovered that the adult pancreas can regenerate beta cells through the spontaneous reprogramming of other mature endocrine cells like alpha, delta, and gamma cells. This unexpected cellular plasticity offers a promising new path for developing regenerative therapies for diabetes and other degenerative diseases.
- Decoding alpha–beta cell interactions: While both cell types have distinct functions—alpha cells secrete glucagon and beta cells insulin—their proximity and interactions suggest they may influence each other’s activity. However, the exact mechanisms of these interactions remain unclear. Researchers aim to explore how direct and/or indirect contacts between alpha and beta cells affect their functional coordination within the islet.
- Protecting pancreatic beta cells: This research focuses on enhancing the resistance of pancreatic beta cells to harmful events, particularly autoimmune attacks, by preventing apoptosis. The goal is to delay the progression toward type 1 diabetes. Investigated strategies include modulating intercellular coupling through surface proteins called connexins, and activating nicotinic receptors using pharmacological agents such as nicotine or choline.
- Bioengineered islet constructs: Research generates insulin-producing cells from stem cells and uses 3D organoid technology to recreate islet-like structures. These are embedded in engineered matrices derived from decellularised fetal tissues that mimic the native pancreatic environment, supporting cell survival and function. To ensure graft viability, functional microvascular networks are bioengineered using recipient-derived endothelial cells. Finally, immune-modulatory scaffolds and immune-evasive cell designs are integrated to promote graft acceptance and long-term tolerance without systemic immunosuppression.
