Abstract

Objective: The use of human fetal pancreatic tissue may provide a potential source of transplantable β-cells as a therapy for type 1 diabetes. Human fetal pancreas has a remarkable capacity to grow and differentiate in vivo and has been shown to reverse diabetes in rodents. However it is known that human fetal pancreas obtained from the 2^nd trimester of gestation is immunogenic and is rejected after transplantation. Tissue obtained from earlier stages might prove to be immune privileged, as has been shown for other tissues.

Research Design and Methods: In this study we determined the immunogenicity of human fetal pancreatic tissue obtained from the 1^st trimester of gestation in a humanized mouse model. A microarray study of immunoregulatory gene expression in 1^st and 2^nd trimester human fetal pancreas was also undertaken.

Results: The analysis of transplanted human fetal pancreata revealed a significantly decreased immunogenicity of the 1^st trimester tissue. The 1^st trimester grafts showed only limited cellular infiltration and contained numerous insulin positive cells, whereas 2^nd trimester tissue was completely infiltrated and rejected. Furthermore an analysis of immunoregulatory genes expressed in 1^st and 2^nd trimester human fetal pancreas by microarray demonstrated the upregulation of several key immunoregulatory genes in the 2nd trimester tissue. This might account for the reduced immunogenicity of the younger tissue.

Conclusions: Our results provide the first indication that the use of 1^st trimester human fetal pancreas for transplantation might increase the survival of the grafts and might decrease the requirement for immunosuppressive drugs.