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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.

SUBMITTER: Fourcade G

PROVIDER: S-EPMC3636635 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Fetal pancreas transplants are dependent on prolactin for their development and prevent type 1 diabetes in syngeneic but not allogeneic mice.

Fourcade Gwladys G Colombo Bruno M BM Grégoire Sylvie S Baeyens Audrey A Rachdi Latif L Guez Fanny F Goffin Vincent V Scharfmann Raphael R Salomon Benoît L BL

Diabetes 20130219 5

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 maintai ...[more]

PMID: 23423564

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Fetal pancreas transplants are dependent on prolactin for their development and prevent type 1 diabetes in syngeneic but not allogeneic mice.

Publications

Fetal pancreas transplants are dependent on prolactin for their development and prevent type 1 diabetes in syngeneic but not allogeneic mice.

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