Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Diabetologia
Published in: Diabetologia 2/2008

01-02-2008 | For Debate

Optimising islet engraftment is critical for successful clinical islet transplantation

Authors: O Korsgren, T Lundgren, M Felldin, A Foss, B Isaksson, J Permert, N H Persson, E Rafael, M Rydén, K Salmela, A Tibell, G Tufveson, B Nilsson

Published in: Diabetologia | Issue 2/2008

Login to get access

Abstract

Clinical islet transplantation is currently being explored as a treatment for persons with type 1 diabetes and hypoglycaemia unawareness. Although ‘proof-of-principle’ has been established in recent clinical studies, the procedure suffers from low efficacy. At the time of transplantation, the isolated islets are allowed to embolise the liver after injection in the portal vein, a procedure that is unique in the area of transplantation. A novel view on the engraftment of intraportally transplanted islets is presented that could explain the low efficacy of the procedure.
Literature
1.
Shapiro AM, Ricordi C, Hering BJ et al (2006) International trial of the Edmonton protocol for islet transplantation. N Engl J Med 355:1318–1330PubMedCrossRef
2.
Keymeulen B, Gillard P, Mathieu C et al (2006) Correlation between beta cell mass and glycemic control in type 1 diabetic recipients of islet cell graft. Proc Natl Acad Sci USA 103:17444–17449PubMedCrossRef
3.
Ryan EA, Paty BW, Senior PA et al (2005) Five-year follow-up after clinical islet transplantation. Diabetes 54:2060–2069PubMedCrossRef
4.
Shapiro AM, Lakey JR, Ryan EA et al (2000) Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 343:230–238PubMedCrossRef
5.
Keymeulen B, Ling Z, Gorus FK et al (1998) Implantation of standardized beta-cell grafts in a liver segment of IDDM patients: graft and recipients characteristics in two cases of insulin-independence under maintenance immunosuppression for prior kidney graft. Diabetologia 41:452–459PubMedCrossRef
6.
van Kampen CA, van de Linde P, Duinkerken G et al (2005) Alloreactivity against repeated HLA mismatches of sequential islet grafts transplanted in non-uremic type 1 diabetes patients. Transplantation 80:118–126PubMedCrossRef
7.
Desai NM, Goss JA, Deng S et al (2003) Elevated portal vein drug levels of sirolimus and tacrolimus in islet transplant recipients: local immunosuppression or islet toxicity. Transplantation 76:1623–1625PubMedCrossRef
8.
Shapiro AM, Gallant HL, Hao EG et al (2005) The portal immunosuppressive storm: relevance to islet transplantation. Ther Drug Monit 27:35–37PubMedCrossRef
9.
Unger RH (1991) Diabetic hyperglycemia: link to impaired glucose transport in pancreatic beta cells. Science 251:1200–1205PubMedCrossRef
10.
Unger RH, Orci L (2002) Lipoapoptosis: its mechanism and its diseases. Biochim Biophys Acta 1585:202–212PubMed
11.
Lee Y, Ravazzola M, Park B, Bashmakov Y, Orci L, Unger R (2007) Metabolic mechanisms of failure of intraportally transplanted pancreatic beta-cells in rats: role of lipotoxicity and prevention by leptin. Diabetes 56:2295–2301PubMedCrossRef
12.
MacDonald IC, Groom AC, Chambers AF (2002) Cancer spread and micrometastasis development: quantitative approaches for in vivo models. Bioessays 24:885–893PubMedCrossRef
13.
Gonda T, Ishida H, Yoshinaga K, Sugihara K (2000) Microvasculature of small liver metastases in rats. J Surg Res 94:43–48PubMedCrossRef
14.
Graf W, Sundin A, Glimelius B, Ahlstrom H, Carlsson J (1992) Induction and quantification of hepatic metastases from a human colonic cancer in the nude rat. Eur J Surg Oncol 18:608–614PubMed
15.
Lehmann R, Zuellig RA, Kugelmeier P et al (2007) Superiority of small islets in human islet transplantation. Diabetes 56:594–603PubMedCrossRef
16.
Dunger A, Korsgren O, Andersson A (1990) DNA replication in mouse pancreatic islets transplanted subcapsularly into the kidney or intraportally into the liver. Influence of unilateral nephrectomy or partial hepatectomy. Transplantation 49:686–689PubMedCrossRef
17.
Nakano M, Yasunami Y, Maki T et al (2000) Hepatocyte growth factor is essential for amelioration of hyperglycemia in streptozotocin-induced diabetic mice receiving a marginal mass of intrahepatic islet grafts. Transplantation 69:214–221PubMedCrossRef
18.
Andersson A, Korsgren O, Jansson L (1989) Intraportally transplanted pancreatic islets revascularized from hepatic arterial system. Diabetes 1(38 Suppl):192–195
19.
Lau J, Jansson L, Carlsson PO (2006) Islets transplanted intraportally into the liver are stimulated to insulin and glucagon release exclusively through the hepatic artery. Am J Transplant 6:967–975PubMedCrossRef
20.
Davalli AM, Maffi P, Socci C et al (2000) Insights from a successful case of intrahepatic islet transplantation into a type 1 diabetic patient. J Clin Endocrinol Metab 85:3847–3852PubMedCrossRef
21.
Oberholzer J, Mathe Z, Bucher P et al (2003) Islet autotransplantation after left pancreatectomy for non-enucleable insulinoma. Am J Transplant 3:1302–1307PubMedCrossRef
22.
Adams AB, Shirasugi N, Durham MM et al (2002) Calcineurin inhibitor-free CD28 blockade-based protocol protects allogeneic islets in nonhuman primates. Diabetes 51:265–270PubMedCrossRef
23.
Adams AB, Shirasugi N, Jones TR et al (2005) Development of a chimeric anti-CD40 monoclonal antibody that synergizes with LEA29Y to prolong islet allograft survival. J Immunol 174:542–550PubMed
24.
Hirshberg B, Mog S, Patterson N, Leconte J, Harlan DM (2002) Histopathological study of intrahepatic islets transplanted in the nonhuman primate model using Edmonton protocol immunosuppression. J Clin Endocrinol Metab 87:5424–5429PubMedCrossRef
25.
Hirshberg B, Montgomery S, Wysoki MG et al (2002) Pancreatic islet transplantation using the nonhuman primate (rhesus) model predicts that the portal vein is superior to the celiac artery as the islet infusion site. Diabetes 51:2135–2140PubMedCrossRef
26.
Kawai T, Sogawa H, Koulmanda M et al (2001) Long-term islet allograft function in the absence of chronic immunosuppression: a case report of a nonhuman primate previously made tolerant to a renal allograft from the same donor. Transplantation 72:351–354PubMedCrossRef
27.
Kenyon NS, Fernandez LA, Lehmann R et al (1999) Long-term survival and function of intrahepatic islet allografts in baboons treated with humanized anti-CD154. Diabetes 48:1473–1481PubMedCrossRef
28.
Koulmanda M, Smith RN, Qipo A, Weir G, Auchincloss H, Strom TB (2006) Prolonged survival of allogeneic islets in cynomolgus monkeys after short-term anti-CD154-based therapy: nonimmunologic graft failure. Am J Transplant 6:687–696PubMedCrossRef
29.
Levisetti MG, Padrid PA, Szot GL et al (1997) Immunosuppressive effects of human CTLA4Ig in a non-human primate model of allogeneic pancreatic islet transplantation. J Immunol 159:5187–5191PubMed
30.
Wijkstrom M, Kenyon NS, Kirchhof N et al (2004) Islet allograft survival in nonhuman primates immunosuppressed with basiliximab, RAD, and FTY720. Transplantation 77:827–835PubMedCrossRef
31.
Moberg L, Johansson H, Lukinius A et al (2002) Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet 360:2039–2045PubMedCrossRef
32.
Kemp CB, Knight MJ, Scharp DW, Ballinger WF, Lacy PE (1973) Effect of transplantation site on the results of pancreatic islet isografts in diabetic rats. Diabetologia 9:486–491PubMedCrossRef
33.
Hiller WF, Klempnauer J, Luck R, Steiniger B (1991) Progressive deterioration of endocrine function after intraportal but not kidney subcapsular rat islet transplantation. Diabetes 40:134–140PubMedCrossRef
34.
Evans MG, Warnock GL, Rajotte RV (1989) Comparison of sites for transplantation of canine pancreatic microfragments. Diabetes Res 10:35–41PubMed
35.
Warnock GL, Dabbs KD, Evans MG, Cattral MS, Kneteman NM, Rajotte RV (1990) Critical mass of islets that function after implantation in a large mammalian. Horm Metab Res Suppl 25:156–161PubMed
36.
Dombrowski F, Mathieu C, Evert M (2006) Hepatocellular neoplasms induced by low-number pancreatic islet transplants in autoimmune diabetic BB/Pfd rats. Cancer Res 66:1833–1843PubMedCrossRef
37.
Bhargava R, Senior PA, Ackerman TE et al (2004) Prevalence of hepatic steatosis after islet transplantation and its relation to graft function. Diabetes 53:1311–1317PubMedCrossRef
38.
Markmann JF, Rosen M, Siegelman ES et al (2003) Magnetic resonance-defined periportal steatosis following intraportal islet transplantation: a functional footprint of islet graft survival. Diabetes 52:1591–1594PubMedCrossRef
39.
Yasunami Y, Lacy PE, Finke EH (1983) A new site for islet transplantation—a peritoneal-omental pouch. Transplantation 36:181–182PubMedCrossRef
40.
Kenyon N, Berman D, O’Neil J et al (2007) Long-term survival of cynomolgus monkey islets implanted in an omental pouch site on tissue engineered scaffolds. Am J Transplant 7 Abstr 1653:572
41.
Wells SA Jr, Gunnells JC, Shelburne JD, Schneider AB, Sherwood LM (1975) Transplantation of the parathyroid glands in man: clinical indications and results. Surgery 78:34–44PubMed
42.
Tominaga Y, Uchida K, Haba T et al (2001) More than 1,000 cases of total parathyroidectomy with forearm autograft for renal hyperparathyroidism. Am J Kidney Dis 38:S168–171PubMed
43.
Axen KV, Pi-Sunyer FX (1981) Long-term reversal of streptozotocin-induced diabetes in rats by intramuscular islet implantation. Transplantation 31:439–441PubMedCrossRef
44.
Dafoe DC, Wang X, Tafra L, Berezniak R, Lloyd RV (1992) Studies of composite grafts of fetal pancreas (FP) and fetal liver (FL) in the streptozotocin-induced diabetic rat. Adv Exp Med Biol 321:171–177PubMed
45.
Weber CJ, Hardy MA, Pi-Sunyer F, Zimmerman E, Reemtsma K (1978) Tissue culture preservation and intramuscular transplantation of pancreatic islets. Surgery 84:166–174PubMed
46.
Jovanovic-Peterson L, Williams K, Brennan M, Rashbaum W, Peterson CM (1989) Studies of human fetal pancreatic allografts in diabetic recipients without immunosuppression. J Diabet Complications 3:107–112PubMedCrossRef
47.
Tuch BE, Sheil AG, Ng AB, Turtle JR (1986) Long-term survival of human fetal pancreatic tissue transplanted into an insulin-dependent diabetic patient. Diabet Med 3:24–28PubMedCrossRef
48.
Johansson U, Elgue G, Nilsson B, Korsgren O (2005) Composite islet-endothelial cell grafts: a novel approach to counteract innate immunity in islet transplantation. Am J Transplant 5:2632–2639PubMedCrossRef
49.
Metadata
Title
Optimising islet engraftment is critical for successful clinical islet transplantation
Authors
O Korsgren
T Lundgren
M Felldin
A Foss
B Isaksson
J Permert
N H Persson
E Rafael
M Rydén
K Salmela
A Tibell
G Tufveson
B Nilsson
Publication date
01-02-2008
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 2/2008
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-007-0868-9

Other articles of this Issue 2/2008

Diabetologia 2/2008 Go to the issue

Short Communication

Retinal haemodynamics in individuals with well-controlled type 1 diabetes

Article

Serum procalcitonin and C-reactive protein concentrations to distinguish mildly infected from non-infected diabetic foot ulcers: a pilot study

Article

Inhibition or deletion of the lipopolysaccharide receptor Toll-like receptor-4 confers partial protection against lipid-induced insulin resistance in rodent skeletal muscle

Article

Effect of macrophage migration inhibitory factor (MIF) gene variants and MIF serum concentrations on the risk of type 2 diabetes: results from the MONICA/KORA Augsburg Case–Cohort Study, 1984–2002

Commentary

One small step for diabetic podopathy

Article

Heparanase induces a differential loss of heparan sulphate domains in overt diabetic nephropathy
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits