title: Fetal pancreas transplants are dependent on prolactin for their development and prevent type 1 diabetes in syngeneic but not allogeneic mice.
abstract: Transplantation of adult pancreatic islets has been proposed to cure type 1 diabetes (T1D). However, it is rarely considered in the clinic because of its transient effect on disease, the paucity of donors, and the requirement for strong immunosuppressive treatment to prevent allogeneic graft rejection. Transplantation of fetal pancreases (FPs) may constitute an attractive alternative because of potential abundant donor sources, possible long-term effects due to the presence of stem cells maintaining tissue integrity, and their supposed low immunogenicity. In this work, we studied the capacity of early FPs from mouse embryos to develop into functional pancreatic islets producing insulin after transplantation in syngeneic and allogeneic recipients. We found that as few as two FPs were sufficient to control T1D in syngeneic mice. Surprisingly, their development into insulin-producing cells was significantly delayed in male compared with female recipients, which may be explained by lower levels of prolactin in males. Finally, allogeneic FPs were rapidly rejected, even in the context of minor histocompatibility disparities, with massive graft infiltration with T and myeloid cells. This work suggests that FP transplantation as a therapeutic option of T1D needs to be further assessed and would require immunosuppressive treatment.
authors: CNRS UMR7211, INSERM U959, Université Pierre et Marie Curie-Paris 6, Paris, France.
authors: Gwladys
authors: G
authors: Fourcade
authors: Bruno M
authors: BM
authors: Colombo
authors: Sylvie
authors: S
authors: Grégoire
authors: Audrey
authors: A
authors: Baeyens
authors: Latif
authors: L
authors: Rachdi
authors: Fanny
authors: F
authors: Guez
authors: Vincent
authors: V
authors: Goffin
authors: Raphael
authors: R
authors: Scharfmann
authors: Benoît L
authors: BL
authors: Salomon
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004622:Embryo, Mammalian; D005260:Female; D005333:Fetus; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000379:methods / Q000473:pathology; D007668:Kidney; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D008822:Mice, Transgenic; D016035:Pancreas Transplantation / Q000276:immunology / Q000379:methods* / Q000473:pathology; D011388:Prolactin / Q000627:therapeutic use*; D012727:Sex Characteristics; D013047:Specific Pathogen-Free Organisms; D016042:Transplantation, Heterotopic / Q000276:immunology / Q000379:methods* / Q000473:pathology; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
chemical_list: D007328:Insulin; D011388:Prolactin