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PROBLEM:
The number of patients receiving care for type 1 and type 2 diabetes has more than doubled since the past decade. In type 1 diabetes, the patient's immune system aberrantly destroys the insulin‐producing β cells of the pancreas. Type 2 diabetes is caused by insulin resistance, progressively reaching the point where β cells can no longer produce enough additional insulin. Cell replacement therapy can be an effective strategy to treat diabetes; however, insufficient supply of β cells from human organ donors is a major issue. Using stem cells as a potential source for deriving new β cells in a safe and easy way has long been awaited for.
RESULTS:
We demonstrated that subpopulations of neurons and adult NP cells express insulin in the brain. Adult NSCs, derived from the HPC and OB, give rise to insulin expressing cells. Adult NPs from DB rats could still generate insulin‐producing cells, and the process requires the activation of NeuroD1 transcription factor via Wnt3 signalling. Under normal circumstances, insulin‐expressing cells of neuronal lineage do not express phenotypic markers of pancreatic β cells. However, after transplantation into the pancreas, these neuronal cells not only increase their production of insulin but also start to express several transcription factors characteristic for pancreatic beta cells. As an approach to stem cell therapy that could be applied without gene transfer techniques, we supplied adult NPs from DB rats into the pancreases of DB rats. We found that this treatment induced insulin expression, reduced blood glucose levels and up‐regulated insulin levels. Removal of these implants led to elevated levels of blood glucose, indicating that transplanting neural progenitor/stem cells into the pancreas could be a useful approach for treating diabetes.
IMPACT:
Our data indicate that adult NSCs are a relevant and safe cell source of insulin‐producing cells. OB‐derived NSCs are particularly useful because of their easily accessible location and their ability to generate insulin‐producing cells, as hippocampal NSCs do. The findings of this study indicate the potential value of this technique for treating human diabetes without gene transfer, and would contribute as a novel strategy to overcome donor issues in cell replacement therapy of diabetes.
INTRODUCTION
There are considerable similarities between the genes expressed in the developing brain and pancreas in mammals...