Pancreatic duct cells show promise for future type 1 diabetes treatment

Researchers have developed a technique to “reprogram” human pancreatic duct-derived cells, allowing them to replace beta cells and secrete insulin in the pancreas while avoiding genetic modification of the target cells, according to study findings presented at the 54th Annual European Society for Paediatric Endocrinology Meeting in Barcelona, Spain.

Researchers from Université Catholique de Louvain said that the human pancreatic duct-derived cells (HDDCs), which were reprogrammed using messenger RNA as a transcription factor, could be further developed to be used for patients with type 1 diabetes.

"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," Philippe Lysy, MD, PhD, of Université Catholique de Louvain, Belgium, said in a press release. “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."

In the study, researcher reprogrammed HDDCs to behave like beta cells and secrete insulin within the pancreas while responding to glucose. The researchers used 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.

The technique allowed the researchers to avoid any potential genetic modification of the target cells, the researchers noted. A mouse model has already been developed and ongoing studies continue.

"With ongoing in vivo studies, we are analyzing the potential of our reprogrammed cells to function and secrete insulin into a body according to blood glucose levels," Lysy said in the press release. "Our objectives are to evaluate the conditions that allow banking of our reprogrammed cells in clinically compatible procedures.”

Reference:

Lysy P, et al. “RNA-based MAFA over-expression is sufficient to drive human pancreatic duct-derived cells toward a b-cell-like phenotype.” Presented at: 54th Annual European Society for Paediatric Endocrinology Meeting; Oct. 1-Oct. 3, 2015; Barcelona.

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