Mouse muscle as an ectopic permissive site for human pancreatic development.
Diabetes
; 62(10): 3479-87, 2013 Oct.
Article
in En
| MEDLINE
| ID: mdl-23835344
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 ß-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 ß-cell development occurs more slowly (weeks) than murine pancreas (days) both by differentiation of pancreatic progenitors and by proliferation of developing ß-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 ß-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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreas
/
Trans-Activators
/
Homeodomain Proteins
/
Diabetes Mellitus, Experimental
/
Basic Helix-Loop-Helix Transcription Factors
/
Nerve Tissue Proteins
Type of study:
Observational_studies
/
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
/
Pregnancy
Language:
En
Journal:
Diabetes
Year:
2013
Document type:
Article
Affiliation country:
France