Cotransplantation with xenogenetic neonatal porcine sertoli cells significantly prolongs islet allograft survival in nonimmunosuppressive rats.
BACKGROUND
In addition to possessing immune privileged properties, Sertoli cells are known to actively suppress responses to cotransplanted cells. An important question is whether this "bystander suppression" is limited to cells of the same origin as the Sertoli cells or whether suppression extends to unrelated cells.


METHODS
Neonatal porcine Sertoli cells (NPSCs) were transplanted with allogeneic islets (Sprague-Dawley rat) into immune competent Wistar rats subsequent to induction of diabetes by alloxan administration.


RESULTS
Although allogeneic islets alone had a mean survival time of 5.67+/-0.94 days, islets cotransplanted with 1.5 x 10 xenogeneic NPSCs displayed a survival of 8.33+/-0.58 days. Increasing the concentration of NPSCs to 1.0 x10 yielded a further increase in survival to 16.33+/-1.53 days. Augmented islet survival was associated with reduced lymphocytic infiltrate and elevated numbers of Sox9 positive cells. Mechanistically, it seemed that Fas ligand was not involved in prolongation of survival because in contrast to adult Sertoli cells, NPSCs lacked expression of this gene.


CONCLUSIONS
These data suggest that xenogeneic Sertoli cells exert a global immune suppressive effect that extends across species barriers in a stringent model of alloimmune rejection. The combination of NPSCs with other immune modulatory regimes may yield novel approaches toward prevention of allo-islet transplant rejection.
Yin
Zhuzeng
Z
Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Chen
Dong
D
Hu
Feng
F
Ruan
Yongle
Y
Li
Junhua
J
Wang
Lu
L
Xiang
Ying
Y
Xie
Lin
L
Wang
Ximo
X
Ichim
Thomas E
TE
Chen
Shi
S
Chen
Gang
G
D000818:Animals; D000831:Animals, Newborn; D024201:Bystander Effect; D002470:Cell Survival; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D006085:Graft Survival; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007165:Immunosuppression Therapy / Q000379:methods*; D007328:Insulin / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D055758:SOX9 Transcription Factor / Q000378:metabolism; D012708:Sertoli Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
D053222:Fas Ligand Protein; D007328:Insulin; D019253:Proto-Oncogene Proteins c-bcl-2; D055758:SOX9 Transcription Factor; D051547:Heme Oxygenase-1