[HTML][HTML] Hyperglycaemia attenuates in vivo reprogramming of pancreatic exocrine cells to beta cells in mice
C Cavelti-Weder, W Li, A Zumsteg… - Diabetologia, 2016 - Springer
C Cavelti-Weder, W Li, A Zumsteg, M Stemann-Andersen, Y Zhang, T Yamada, M Wang…
Diabetologia, 2016•SpringerAims/hypothesis Reprogramming of pancreatic exocrine to insulin-producing cells by viral
delivery of the genes encoding transcription factors neurogenin-3 (Ngn3),
pancreas/duodenum homeobox protein 1 (Pdx1) and MafA is an efficient method for
reversing diabetes in murine models. The variables that modulate reprogramming success
are currently ill-defined. Methods Here, we assess the impact of glycaemia on in vivo
reprogramming in a mouse model of streptozotocin-induced beta cell ablation, using …
delivery of the genes encoding transcription factors neurogenin-3 (Ngn3),
pancreas/duodenum homeobox protein 1 (Pdx1) and MafA is an efficient method for
reversing diabetes in murine models. The variables that modulate reprogramming success
are currently ill-defined. Methods Here, we assess the impact of glycaemia on in vivo
reprogramming in a mouse model of streptozotocin-induced beta cell ablation, using …
Aims/hypothesis
Reprogramming of pancreatic exocrine to insulin-producing cells by viral delivery of the genes encoding transcription factors neurogenin-3 (Ngn3), pancreas/duodenum homeobox protein 1 (Pdx1) and MafA is an efficient method for reversing diabetes in murine models. The variables that modulate reprogramming success are currently ill-defined.
Methods
Here, we assess the impact of glycaemia on in vivo reprogramming in a mouse model of streptozotocin-induced beta cell ablation, using subsequent islet transplantation or insulin pellet implantation for creation of groups with differing levels of glycaemia before viral delivery of transcription factors.
Results
We observed that hyperglycaemia significantly impaired reprogramming of exocrine to insulin-producing cells in their quantity, differentiation status and function. With hyperglycaemia, the reprogramming of acinar towards beta cells was less complete. Moreover, inflammatory tissue changes within the exocrine pancreas including macrophage accumulation were found, which may represent the tissue’s response to clear the pancreas from insufficiently reprogrammed cells.
Conclusions/interpretation
Our findings shed light on normoglycaemia as a prerequisite for optimal reprogramming success in a diabetes model, which might be important in other tissue engineering approaches and disease models, potentially facilitating their translational applications.
Springer