title: Mouse muscle as an ectopic permissive site for human pancreatic development.
abstract: 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.
authors.affiliation: INSERM U845, Research Center Growth and Signalling, Faculté de Médecine Cochin, Université Paris Descartes, Paris, France.
authors.forename: Carmen
authors.initials: C
authors.lastname: Capito
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Simon
authors.forename: Virginie
authors.initials: V
authors.lastname: Aiello
authors.forename: Anne
authors.initials: A
authors.lastname: Clark
authors.forename: Yves
authors.initials: Y
authors.lastname: Aigrain
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravassard
authors.forename: Raphael
authors.initials: R
authors.lastname: Scharfmann
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018014:Gene Transfer Techniques; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000196:embryology / Q000502:physiology; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology* / Q000196:embryology / Q000473:pathology; D011247:Pregnancy; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; C498695:NEUROG3 protein, human; C407737:Neurog3 protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein