Mouse Muscle As an Ectopic Permissive Site for Human Pancreatic Development
- Carmen Capito1,
- Marie-Thérèse Simon1,
- Virginie Aiello1,
- Anne Clark2,
- Yves Aigrain3,
- Philippe Ravassard4 and
- Raphael Scharfmann1⇑
- 1INSERM U845, Research Center Growth and Signalling, Faculté de Médecine Cochin, Université Paris Descartes, Paris, France
- 2Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, U.K.
- 3Necker Enfants Malades University Hospital, Université Paris Descartes, Paris, France
- 4Biotechnology and Biotherapy Team, Université Pierre et Marie Curie-Paris 6, Biotechnology and Biotherapy Team, Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière, UMRS 975, CNRS, UMR 7225, INSERM U975, Paris, France.
- Corresponding author: Raphael Scharfmann, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-0554/-/DC1.
- Received April 8, 2013.
- Accepted June 26, 2013.
- © 2013 by the American Diabetes Association.
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