Reduced immunogenicity of first-trimester human fetal pancreas.
OBJECTIVE
The use of human fetal pancreatic tissue may provide a potential source of transplantable beta-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 second 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.


METHODS
In this study, we determined the immunogenicity of human fetal pancreatic tissue obtained from the first trimester of gestation in a humanized mouse model. A microarray study of immunoregulatory gene expression in first- and second-trimester human fetal pancreas was also undertaken.


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


CONCLUSIONS
Our results provide the first indication that the use of first-trimester human fetal pancreas for transplantation might increase the survival of the grafts and might decrease the requirement for immunosuppressive drugs.
Diabetes Transplant Unit, The Prince of Wales Hospital and The University of New South Wales, Sydney, New South Wales 2031, Australia.
Kerstin
K
Brands
Emily
E
Colvin
Lindy J
LJ
Williams
Rennian
R
Wang
Richard B
RB
Lock
Bernard E
BE
Tuch
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D016332:Fetal Tissue Transplantation / Q000276:immunology*; D005333:Fetus; D005786:Gene Expression Regulation; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010179:Pancreas / Q000196:embryology / Q000276:immunology* / Q000378:metabolism; D016035:Pancreas Transplantation / Q000276:immunology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second
D015815:Cell Adhesion Molecules; D018925:Chemokines; D006680:HLA Antigens