Mouse muscle as an ectopic permissive site for human pancreatic development

C Capito, MT Simon, V Aiello, A Clark, Y Aigrain… - Diabetes, 2013 - Am Diabetes Assoc
C Capito, MT Simon, V Aiello, A Clark, Y Aigrain, P Ravassard, R Scharfmann
Diabetes, 2013Am Diabetes Assoc
While sporadic human genetic studies have permitted some comparisons between rodent
and human pancreatic development, the lack of a robust experimental system has not
permitted detailed examination of human pancreatic development. We previously developed
a xenograft model of immature human fetal pancreas grafted under the kidney capsule of
immune-incompetent mice, which allowed the development of human pancreatic β-cells.
Here, we compared the development of human and murine fetal pancreatic grafts either …
While sporadic human genetic studies have permitted some comparisons between rodent and human pancreatic development, the lack of a robust experimental system has not permitted detailed examination of human pancreatic development. We previously developed a xenograft model of immature human fetal pancreas grafted under the kidney capsule of immune-incompetent mice, which allowed the development of human pancreatic β-cells. Here, we compared the development of human and murine fetal pancreatic grafts either under skeletal muscle epimysium or under the renal capsule. We demonstrated that human pancreatic β-cell development occurs more slowly (weeks) than murine pancreas (days) both by differentiation of pancreatic progenitors and by proliferation of developing β-cells. The superficial location of the skeletal muscle graft and its easier access permitted in vivo lentivirus-mediated gene transfer with a green fluorescent protein-labeled construct under control of the insulin or elastase gene promoter, which targeted β-cells and nonendocrine cells, respectively. This model of engraftment under the skeletal muscle epimysium is a new approach for longitudinal studies, which allows localized manipulation to determine the regulation of human pancreatic development.
Am Diabetes Assoc