scholarly journals Development of an Immunoprivileged Site to Prolong Islet Allograft Survival

2002 ◽  
Vol 11 (6) ◽  
pp. 547-552 ◽  
Author(s):  
Tatsuya Kin ◽  
Ray V. Rajotte ◽  
Jannette M. Dufour ◽  
Gregory S. Korbutt
Keyword(s):  
Sertoli Cells ◽  
Critical Role ◽  
Graft Function ◽  
Allograft Survival ◽  
Islet Allograft ◽  
Mouse Islet ◽  
Systemic Immunosuppression ◽  
Composite Grafts ◽  
Islet Allografts

Sertoli cells (SC) play a critical role in the maintenance of the immunoprivileged environment of the testis. We hypothesized that preengrafting SC would allow one to develop a vascularized immunoprivileged ectopic site that provides protection for mouse islet allografts. SC, prepared from 9-day Balb/c mice, were transplanted under the kidney capsule in adult Balb/c mice. After SC engraftment (~30 days), mice were rendered diabetic and subsequently implanted with Balb/c or CBA/J islets directly adjacent to the established SC grafts. Preengrafted SC (5.7 ± 0.2 × 106) had no adverse effect on syngeneic islet graft function. When allogeneic islets were transplanted into the immunoprivileged ectopic site created by preengrafting 6.4 ± 0.3 × 106 SC, mean graft survival was slightly prolonged (32.4 ± 6.0 days) compared with control mice that received allogeneic islets alone (16.3 ± 1.5 days; p = 0.329). In contrast, when 4.8 ± 0.4 × 106 SC were preengrafted, islet allograft survival was significantly prolonged (66.1 ± 9.8 days; p = 0.001). Four of eight mice, preimplanted with 4.8 ± 0.4 × 106 SC, remained normoglycemic throughout the follow-up period (83.8 ± 8.6 days) and returned to a diabetic state only when the kidneys bearing the composite grafts were removed. Transplantation of islets into an immunoprivileged ectopic site created by preengrafting SC did not affect islet function and, moreover, provided a means of developing an immunopriveliged ectopic site that permits prolonged islet allograft survival without systemic immunosuppression.

scholarly journals Hair Follicle Dermal Sheath Derived Cells Improve Islet Allograft Survival without Systemic Immunosuppression

2015 ◽  
Vol 2015 ◽  
pp. 1-15
Author(s):  
Xiaojie Wang ◽  
Jianqiang Hao ◽  
Gigi Leung ◽  
Trisia Breitkopf ◽  
Eddy Wang ◽  
...  
Keyword(s):  
Beta Cell ◽  
Hair Follicle ◽  
Type I ◽  
Allograft Survival ◽  
Islet Allograft ◽  
Systemic Immunosuppression ◽  
Islet Allografts ◽  
Local Immunosuppression ◽  
Group 2 ◽  
Group 1

Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1) or fibroblasts (FB, group 2) under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days,P<0.001) without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation.

Effect of Fusidic Acid on Pancreatic Islet Allograft Rejection

1997 ◽  
Vol 6 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Josá F. Mendola ◽  
Helena Corominola ◽  
Enric Esmatjes ◽  
Alex Saenz ◽  
Laureano Fernandez-Cruz ◽  
...  
Keyword(s):  
Pancreatic Islet ◽  
Fusidic Acid ◽  
Allograft Rejection ◽  
Diabetic Rats ◽  
Allograft Survival ◽  
Islet Allograft ◽  
Islet Allografts ◽  
Acinar Tissue

We examined in fully mismatched rats, the survival of pancreatic islet allografts in recipients treated with either fusidic acid (FA), an antistaphyllococcal antibiotic that has been shown to possess an immunosuppressive effect in vitro and in vivo, or cyclosporin-A (CsA). Islets were isolated by collagenase digestion, separated from acinar tissue by handpicking under a dissecting microscope and transplanted into the liver by portal vein injection of streptozotocin(STZ)-induced diabetic rats. The results indicated that while a temporary immunosuppression with CsA achieved an indefinite islet allograft survival, FA administered to recipients daily was not able to prevent islet allograft rejection across a major histocompatibility barrier. We conclude that despite the fact that fusidic acid has been claimed to act as an immunosuppressant drug in vitro with effects similar to those of CsA, unlike CsA, FA given either orally or by s.c. injection was not effective to prolong islet allograft survival in vivo. Copyright © 1997 Elsevier Science Inc.

scholarly journals Decreased Survival of Islet Allografts in Rats with Advanced Chronic Complications of Diabetes

2002 ◽  
Vol 11 (7) ◽  
pp. 707-713 ◽  
Author(s):  
Wayne V. Moore ◽  
Karen Bieser ◽  
Zhoahui Geng ◽  
Pei Y. Tong ◽  
Karen Kover
Keyword(s):  
Islet Transplantation ◽  
Acute Onset ◽  
Human Islet ◽  
Allograft Survival ◽  
Chronic Complications ◽  
Islet Allograft ◽  
Complications Of Diabetes ◽  
Onset Diabetes ◽  
Islet Allografts ◽  
Human Islet Transplantation

Successful islet transplantation has been possible in experimental animals in contrast to humans. One difference between animal models of diabetes and human islet transplantation is the presence of advanced chronic complications in humans. Even longer-term follow-up of islet transplantation in humans according to the Edmonton protocol suggests that advanced chronic complications may adversely affect allograft survival with the glucocorticoid-free immunosuppressive regimen as well. We developed a rat model of chronic complications of diabetes and compared islet allograft survival in rats with advanced chronic complications to age-matched control rats with acute onset diabetes. Islets were transplanted at either the renal supcapsular, intrahepatic, or intramuscular location. The survival of islet allografts in rats with chronic complications was decreased at all sites compared with the age-matched controls. The best survival in the rats with advanced chronic complications occurred at the renal subcapsular site. Blood sugar measurements indicated impaired glucose tolerance in most of the rats with chronic complications and surviving renal subcapsular islet allograft. Histological and gross examination of the surviving renal subcapsular islet allografts indicated disordered angiogenesis in the rats with chronic complications. Rats with successful intrahepatic islet allografts and the respective age-matched controls had comparable blood sugars. Survival of islet allografts at the intramuscular site was poor in rats with chronic complications or acute onset diabetes. We conclude that the structural or metabolic abnormalities associated with chronic poor control of diabetes impair islet allograft survival and function. This should be considered as a possible explanation for failure of islet allograft survival in human islet transplantation.

Cotransplantation With Xenogenetic Neonatal Porcine Sertoli Cells Significantly Prolongs Islet Allograft Survival in Nonimmunosuppressive Rats

2009 ◽  
Vol 88 (3) ◽  
pp. 339-345 ◽  
Author(s):  
Zhuzeng Yin ◽  
Dong Chen ◽  
Feng Hu ◽  
Yongle Ruan ◽  
Junhua Li ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Allograft Survival ◽  
Islet Allograft

Treatment With an Interleukin-1 Receptor Antagonist Protein Prolongs Mouse Islet Allograft Survival

Diabetes ◽  
1993 ◽  
Vol 42 (12) ◽  
pp. 1845-1851 ◽  
Author(s):  
J.-O. Sandberg ◽  
D. L. Eizirik ◽  
S. Sandler ◽  
D. E. Tracey ◽  
A. Andersson
Keyword(s):  
Receptor Antagonist ◽  
Interleukin 1 ◽  
Allograft Survival ◽  
Islet Allograft ◽  
Mouse Islet ◽  
Interleukin 1 Receptor Antagonist

scholarly journals Blockade of both B7-H4 and CTLA-4 co-signaling pathways enhances mouse islet allograft survival

Islets ◽  
2012 ◽  
Vol 4 (4) ◽  
pp. 284-295 ◽  
Author(s):  
Xiaojie Wang ◽  
Jianqiang Hao ◽  
Daniel L. Metzger ◽  
Alice Mui ◽  
I-Fang Lee ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Allograft Survival ◽  
Islet Allograft ◽  
Mouse Islet

scholarly journals Effect of a New Immunosuppressive Agent, Fty720, on Survival of Islet Allografts

1998 ◽  
Vol 7 (4) ◽  
pp. 403-406 ◽  
Author(s):  
Toru Yamasaki ◽  
Kazutomo Inoue ◽  
Hiroyuki Hayashi ◽  
Yuanjun Gu ◽  
Hiroshi Setoyama ◽  
...  
Keyword(s):  
Immunosuppressive Agent ◽  
Control Group ◽  
Study Group ◽  
Distilled Water ◽  
Allograft Survival ◽  
Innovative Drug ◽  
Potent Effect ◽  
Islet Allograft ◽  
Islet Allografts ◽  
And Control

A newly developed immunosuppressant, FTY720, has a unique mechanism that is quite different from those of conventional immunosuppressants, and is presumed to be mediated through decreases in the number of peripheral lymphocytes, especially helper T cells. This study was performed to ascertain whether this innovative drug could prolong islet allograft survival. The donors were inbred Lewis rats and the recipients were ACI rats rendered hyperglycemic with intravenous streptozotocin. In the study group, FTY720 dissolved in distilled water was orally administered at a dose of 5 mg/kg to the recipient ACI rats 1 day before and on the day of grafting. In the control group, only distilled water was orally administered to the recipient ACI rats on the day before and the day of grafting. Two thousand islets were transplanted into the portal vein of the recipient rats in the study and control groups immediately after isolation. The graft survival time in the study group was significantly longer than that in the control group, indicating that FTY720 retains a potent effect on the prolongation of islet allograft survival. FTY720 could become a useful immunosuppressant for future clinical islet allotransplantation.

Treatment with an interleukin-1 receptor antagonist protein prolongs mouse islet allograft survival

Diabetes ◽  
1993 ◽  
Vol 42 (12) ◽  
pp. 1845-1851 ◽  
Author(s):  
J. O. Sandberg ◽  
D. L. Eizirik ◽  
S. Sandler ◽  
D. E. Tracey ◽  
A. Andersson
Keyword(s):  
Receptor Antagonist ◽  
Interleukin 1 ◽  
Allograft Survival ◽  
Islet Allograft ◽  
Mouse Islet ◽  
Interleukin 1 Receptor Antagonist

Donor-Specific Unresponsiveness Induced by Intraportal Grafting and FK506 in Rat Islet Allografts: Importance of Low Temperature Culture and Transplant Site on Induction and Maintenance

1994 ◽  
Vol 3 (1) ◽  
pp. 75-82 ◽  
Author(s):  
Yohichi Yasunami ◽  
Shinichiroh Ryu ◽  
Masao Ueki ◽  
Takeshi Arima ◽  
Takafumi Kamei ◽  
...  
Keyword(s):  
Low Temperature ◽  
Survival Time ◽  
Third Party ◽  
Allograft Survival ◽  
Islet Allograft ◽  
Kidney Capsule ◽  
Mean Survival Time ◽  
Islet Allografts ◽  
Specific Strain ◽  
Transplant Site

Previously we demonstrated prolongation of islet allograft survival in rat by administration of FK506 to the recipients. The purpose of the present study was to determine whether specific immune unresponsiveness had been induced and to determine the effects of low temperature culture of donor islets as well as the transplant site on the induction of immune unresponsiveness. At 90 days after transplantation, normoglycemic recipients bearing functional intrahepatic grafts were made diabetic again with streptozotocin (STZ) and donor specific or third party islets were transplanted either into the liver or beneath the kidney capsule. When fresh islets were used as donors in initial transplantation in conjunction with FK506, intrahepatic re-transplants of fresh islets from the donor-specific strain in the absence of FK506 maintained normoglycemia for more than 60 days, while third party transplants (n = 3) were rejected within 1 wk. In contrast to intrahepatic regrafts, all the renal subcapsular regrafts from the donor-specific strain (n = 3) were rejected with mean survival time of 12.7 ± 6.4 days. When cultured (24°C, 7 days) islets were used for initial transplantation in conjunction with FKS06, re-transplants of fresh or cultured islets from the donor specific strain beneath the kidney capsule maintained normoglycemic in 3 out of 6 or all (n = 4) of the recipients, respectively. Cultured third party regrafts beneath the kidney capsule (n = 2) were rejected at 9 days. These findings clearly demonstrate that immune unresponsiveness induced by intraportal grafting of islets in conjunction with FK506 was donor specific and indicate that cultured islets appear more tolerogenic when used at the initial transplant and less immunogenic when used as regrafts. The present study also indicates the importance of transplant site in induction and maintenance of donor specific unresponsiveness.

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