Human Islet Isolation and Allotransplantation in 22 Consecutive Cases 1, 2

Ricordi, Camillo; Tzakis, Andreas G.; Carroll, P. B.; Zeng, Yijun; Rilo, Horacio; Alejandro, Rodolfo; Shapiro, Ron; Fung, John J.; Demetris, Anthony J.; Mintz, Daniel H.; Starzl, Thomas E.

doi:10.1097/00007890-199202010-00027

Cited by 230 publications

(112 citation statements)

References 26 publications

(32 reference statements)

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…9 In the 1990s, the Diabetes Research Institute in Miami performed the first series of six successful islet allograft transplantations in humans, with subsequent unequivocal evidence of the long-term reversal of diabetes. 10,11 A few of these patients showed many years of insulin independence, as confirmed in reports from the Milan and Miami groups. 12,13 Thanks to the efforts of Hering and Bretzel, who in the meantime introduced the use of endotoxin-free re-agents, 14,15 the Islet Transplantation Registry (ITR) became an important source of information for researchers.…”

supporting

confidence: 69%

The Role of Islet Cell Transplantation in the Management of Diabetes

Fiorina¹

2008

European Endocrinology

View full text Add to dashboard Cite

Islet cell transplantation has recently emerged as one the most promising therapeutic approaches for improving glycometabolic control in patients with diabetes and, in many cases, obtaining insulin independence.However, investigators are still debating whether islet transplantation should be considered as an option only in specific single cases. In this brief article I will review the state of the art of islet transplantation, as well as the many problems surrounding the field and the obstacles that islets face after transplantation. The rate of insulin independence one year after islet cell transplantation has significantly improved in recent years (60% at one year post-transplantation compared with 15% in previous years). Recent data indicate that restoration of insulin secretion after islet cell transplantation is associated with an improvement in quality of life, with a reduction in hypoglycaemic episodes and (potentially) long-term complications of diabetes. Once clinical islet transplantation has been successfully established, this treatment could even be offered to patients with diabetes long before the onset of complications of diabetes.The master treatment for patients affected by type 1 diabetes is insulin therapy, which was a life-saving breakthrough when it was introduced.Unfortunately, insulin treatment cannot fully prevent chronic complications related to diabetes, and intensive insulin treatment to improve metabolic control increases the risk of fatal hypoglycaemic episodes. [1][2][3][4] The hypothesis that the replacement of the endocrine pancreas by transplanting fragments of insulin-producing tissue could be helpful is not new. 5 Pancreatic fragments can produce their own insulin with closely controlled and finely timed insulin release. Islet transplantation is a relatively new medical procedure to substitute pancreatic function; unfortunately, the evident contradictions prevented islet therapy from becoming a real option for patients with type 1 diabetes. The absence of standardised protocols and the differences in inclusion criteria and immunosuppressive regimens among studies prevents islet transplantation from becoming the gold standard for treatment.The first attempt to transplant pieces of the pancreas was made by Watson in 1893, who injected sheep pancreatic fragments into a 15-year-old boy. This first islet xenograft, which preceded the historic discovery of insulin by Banting and Best in 1922, was a clear failure but, in retrospect, was audacious. Paul E Lacy can without doubt be considered the inventor of islet transplantation and the first method for isolating islets from rodent pancreata. 6 A milestone was reached in 1972, when Ballinger and Lacy reported that islet isografts from normal rats could reverse streptozotocin-induced diabetes in the animals. 7 During the 1980s, different reports suggested, for the first time, the feasibility of islet transplantation in humans by transplanting autologous islets in patients with painful and chronic pancreatitis who had undergone total panc...

show abstract

supporting

confidence: 69%

The Role of Islet Cell Transplantation in the Management of Diabetes

Fiorina¹

2008

European Endocrinology

View full text Add to dashboard Cite

show abstract

“…Islets were isolated from 5 to 7-dayold newborn Sprague-Dawley rats and BALB/C mice as described previously [26]. Human islets were isolated from two human cadaveric donors (gift from Dr. Camillo Ricordi, University of Miami, Medical School) by collagenase digestion as described previously [27]. Rat pituitary, pancreatic islets, brains, thymus, spleen and adrenal tissues were also isolated, homogenized and digested into single cells.…”

Section: Methodsmentioning

confidence: 99%

Humoral autoreactivity to an alternatively spliced variant of ICA512/IA-2 in Type I diabetes

et al. 2000

View full text Add to dashboard Cite

“…Furthermore, FK506 has been used in clinical islet allotransplantation with mixed results. 16 In conclusion, FK506 is a potent, effective immunosuppressant for islet allograft TR in diabetic rats across the MHC barrier. The immunosuppressive effect was observed in recipients of islets from more than one donor strain and in presensitized recipients.…”

Section: Discussionmentioning

confidence: 88%

Successful islet allotransplantation in diabetic rats immunosuppressed with FK506: A functional and immunological study

et al. 1994

View full text Add to dashboard Cite

The effect of a novel immunosuppressive agent, FK506, on fresh islet allografts was evaluated in diabetic rats across major histocompatibility complex (MHC) barriers with respect to the transplantation (TR) site, islet source, treatment regimen, and antidonor antibody (Ab) titers of the recipients after TR. The functional periods of Wistar (Wi) islets transplanted under kidney capsule (KC) or intraportally (IPo) and of a mixture of Wi and Lewis (Le) islets under KC or IPo in nonimmunosuppressed ACI rat recipients were 6.9 ± 0.4 (n = 7), 6.4 ± 0.5 (n = 7), 5.6 ± 0.4 (n = 7), and 6.2 ± 0.4 (n = 5) days, respectively. FK506 treatment at 1 mg/kg/d intramuscularly (IM) for 2 weeks (protocol I) following islet TR under KC and IPo significantly prolonged the allograft function to more than 71.8 ± 11.3 (n = 10) and 161.7 ± 18.6 (n = 11) days, respectively. Additional treatment with FK506 at 1 mg/kg/wk (protocol II) further increased the islet survival under KC to more than 212.6 ± 22.3 (n = 8) days. With this FK506 treatment protocol, the Wi + Le mixed-islet allograft function was extended to more than 106.1 ± 10.5 (n = 7) and 167.9 ± 28.6 (n = 7) days under KC and IPo, respectively. Nephrectomy in 8/8 ACI rats with long-term-functioning Wi (n = 6) and Wi + Le (n = 2) islet allografts resulted in their return to hyperglycemia. Immunohistochemical staining showed abundant insulin-positive cells at the graft site, with small numbers of CD4-and CD8-positive cells present in the vicinity of the normal-appearing islets. Macrophages were not detected. The immunosuppressive effect of FK506 was further tested In ACI rats presensitized by a previous Wi islet TR. When the duration between the first and second TR under KC was 114.3 ± 20.5 days, protocol II treatment significantly prolonged the graft function to more than 152.9 ± 28.7 (n = 8) days. However, with a short duration of about 2 weeks between the two TRs, the same FK506 protocol achieved islet graft function of 14.0 ± 3.8 days (n = 7). Additional immunosuppression with cyclophosphamide did not further improve the survival time. Antidonor Abs detected in ACI recipients of Wi islet allografts were significantly lower in the FK506-treated animals compared with the nontreatmant group. Wi and Le skin grafts performed in three ACI rats with long-term-functioning Wi islets IPo caused the rejection of the islet allografts. Skin grafts were also rejected in the first-set fashion. Six ACI recipients with longterm-functioning IPo Wi islet allografts were rendered hyperglycemic by streptozocin (STZ) injection. Long-term normoglycemia without further FK506 immunosuppression was achieved following retransplantation with fresh Wi islets IPo (n = 2), but not under KC (n = 2). The results of the present study indicate that FK506 was an effective immunosuppressant for islet allotransplantation in diabetic ACI rats across MHC barriers with islets from two donor strains, as well as in sensitized recipients whose antidonor activities had subsided. The efficacy of the immunosuppressio...

show abstract

Human Islet Isolation and Allotransplantation in 22 Consecutive Cases 1, 2

Cited by 230 publications

References 26 publications

The Role of Islet Cell Transplantation in the Management of Diabetes

The Role of Islet Cell Transplantation in the Management of Diabetes

Humoral autoreactivity to an alternatively spliced variant of ICA512/IA-2 in Type I diabetes

Successful islet allotransplantation in diabetic rats immunosuppressed with FK506: A functional and immunological study

Contact Info

Product

Resources

About