A new technique to produce cells with insulin-secretion capabilities has been developed, according to research presented today at the 54th Annual European Society for Paediatric Endocrinology Meeting. The technique could be further developed to be used in the transplantation for patients with type 1 diabetes.
It is well established that in type 1 diabetes, the body's immune system mistakenly attacks and destroys beta cells in the pancreas. These unique cells are responsible in producing, storing and secreting insulin– the hormone that regulates levels of glucose in the blood. Currently one of the most promising therapies in the fight against diabetes is the replacement of beta cells. In the replacement therapy for type 1 diabetes, researchers from Université Catholique de Louvain have previously shown that human pancreatic duct-derived cells (HDDCs) are an attractive source of cells. The cells are found in the adult pancreas and are progenitor cells – cells that have a tendency to differentiate into specific types of cells.
In this study, the group reprogrammed HDDCs to behave like beta cells and secrete insulin within the pancreas, whilst responding to glucose. The researchers used messenger RNA (mRNA) of a transcription factor – a protein that controls which genes are turned off or on in the genome – called MAFA. The mRNA is transformed into protein before binding to cellular DNA in order to orchestrate the changes in cellular functions.
This technique allowed the researchers to avoid any potential genetic modification of the target cells. "The novelty of our work resides in the use of adult tissue that avoids the risks related to stem cells, such as cancer, and of a protocol that modifies the cells with a direct action on DNA without any structural modification," said lead investigator Professor Philippe Lysy. "Our system for cellular reprogramming with transcription factors using mRNA opens doors for experiments in other scientific fields with the objective to produce cells with a new function in the context of diseases with a loss-of-function."
The group has already developed a mouse model that allows them to transplant their manufactured cells into the diabetic mice and follow-up on their disease. At the same time, the group uses a 'good laboratory practice (GLP)' facility to produce batches of cells that could eventually be transplanted into human patients with diabetes. "With ongoing in vivo studies, we are analysing the potential of our reprogrammed cells to function and secrete insulin into a body according to blood glucose levels," Professor Lysy said. "Our objectives are to evaluate the conditions that allow banking of our reprogrammed cells in clinically compatible procedures," he said.