The Favorable Outcome of Human Islet Transplantation in Korea: Experiences of 10 Autologous Transplantations

Lee, Byung Wan; Jee, Jae Hwan; Heo, Jin Seok; Choi, Seong Ho; Jang, Kee Taek; Noh, Jae Hyung; Jeong, In Kung; Oh, Seung Hoon; Ahn, You Ran; Chae, Hee Young; Min, Yong Ki; Chung, Jae Hoon; Lee, Moon Kyu; Lee, Myung-Shik; Kim, Kwang Won

doi:10.1097/01.tp.0000158427.07084.c5

Cited by 40 publications

(25 citation statements)

References 29 publications

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“…The results after implantation of autologous islets have been strikingly better than those for allogeneically transplanted islets [14,15]. In fact, only a third of the number of islets seems to be needed to attain a similar degree of insulin independence in the former case [14,15]. Long-term graft survival is also markedly better for autotransplanted islets [16].…”

mentioning

confidence: 66%

“…necessity of pancreatectomy for severe chronic pancreatitis or benign pancreatic tumours [14,15]. The results after implantation of autologous islets have been strikingly better than those for allogeneically transplanted islets [14,15]. In fact, only a third of the number of islets seems to be needed to attain a similar degree of insulin independence in the former case [14,15].…”

mentioning

confidence: 92%

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confidence: 99%

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Improved vascular engraftment and function of autotransplanted pancreatic islets as a result of partial pancreatectomy in the mouse and rat

2007

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Aims/hypothesis The few patients subjected to autotransplantation of pancreatic islets after pancreatectomy usually become normoglycaemic after using islets from the resected organ only, whereas allogeneic recipients usually require at least two grafts to retain normoglycaemia. Previous experimental studies have demonstrated that islets transplanted to non-pancreatectomised recipients acquire a markedly decreased blood vessel density, which leads to a hypoxic microenvironment. The aim of the present study was to test the hypothesis that autotransplanted islets have better vascular engraftment and function as a result of the pancreatic surgery involved. Materials and methods In the present study, athymic mice and inbred rats were subjected to a 60% pancreatectomy and transplanted with human or rat islets, respectively, 4 days later. Control animals underwent sham surgery. Blood flow, oxygen tension, vascular density and endocrine volume in the islet grafts were measured 1 month after transplantation. Separate grafts were used for perfusion experiments and for assessment of beta cell proliferation and endocrine cellular apoptosis at different time periods after transplantation.Results Islet grafts in partially pancreatectomised recipients had an increased blood flow, oxygen tension, blood vessel density and endocrine mass 1 month post-transplantation compared with control animals. They also exhibited increased insulin release in perfusion experiments performed 1 month post-transplantation, and decreased cellular apoptosis early after transplantation. Conclusions/interpretation The present study shows that the pancreatectomy procedure itself has beneficial effects on the engraftment of transplanted human and rat islets. Our results provide an additional explanation, besides diminished immunological responses, of the much better outcome of islet autotransplantations compared with allogeneic transplantations in the clinic.

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confidence: 66%

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confidence: 92%

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Improved vascular engraftment and function of autotransplanted pancreatic islets as a result of partial pancreatectomy in the mouse and rat

2007

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“…Unlike allogenic islet transplantation where islets are transplanted from an unrelated individual to a member of the same species, and which requires immunosuppressive treatment, autologous islet recipients transplanted with 250,000 islets can achieve a stable euglycemic state (70-80%) (Boker et al, 2001;Lee et al, 2005) and thus this is considered to be an ideal model type for studying islet engraftment. However, it is likely that no more than 30% of the transplanted islet cell mass becomes engrafted in type 1 diabetic recipients, though they ultimately compose about 50% of the beta cell mass present in a normal individual (Davalli et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Effective glycemic control achieved by transplanting non-viral cationic liposome-mediated VEGF-transfected islets in streptozotocin-induced diabetic mice

Chae

Lee²,

Oh³

et al. 2005

Exp Mol Med

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Hypoxic damage is one of the major causes of islet graft failure and VEGF is known to play a crucial role in revascularization. To address the effectiveness of a cationic lipid reagent as a VEGF gene carrier, and the beneficial effect of VEGF-transfected islets on glycemic control, we used effectene lipid reagent in a transfection experiment using mouse islets. Transfection efficiencies were highest for 4 µg/µL cDNA and 25 µL effectene and cell viabilities were also satisfactory under this condition, and the overproduction of VEGF mRNA and protein were confirmed from conditioned cells. A minimal number of VEGF-transfected islets (100 IEQ/animal) were transplanted into streptozotocin (STZ)-induced diabetic mice. Hyperglycemia was not controlled in the islet transplantation (IT)-alone group (0/8) (nondiabetic glucose mice number/total recipient mice number) or in the IT-pJDK control vector group (0/8). However, hyperglycemia was completely abrogated in the IT-pJDK-VEGF transduced group (8/8), and viable islets and increased VEGF-transfected grafts vascularization were observed in renal capsules. These studies support the usefulness of VEGFtransfected islet delivery using a cationic lipid reagent to achieve euglycemia using a minimal number of islets.

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“…As far as metabolic studies after TP-IAT, largely focused on glycemic control and need or lack of need for exogenous insulin and the value of functioning islets even if the mass is insufficient for insulin-independence, many have been published (Ahmad et al, 2005;Bellin et al, 2008;Bellin et al, 2009;Berney et al, 2000;Farney et al, 1998;Jie et al, 2005;Jung et al, 2009;Kendall et al, 1997;Lee et al, 2005;Leone et al, 1998;Ngo et al, 2011;Pyzdrowski et al, 1992;Robertson et al, 2001;Robertson, 2010a;Sutherland et al, 2008;Teuscher et al, 1998).…”

Section: Metabolic Considerationsmentioning

confidence: 99%

Total Pancreatectomy and Islet Autotransplantation for Chronic Pancreatitis

E.R.¹,

Bellin²,

Juan³

et al. 2012

Chronic Pancreatitis

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The Favorable Outcome of Human Islet Transplantation in Korea: Experiences of 10 Autologous Transplantations

Abstract: Even partial islet graft function can have a beneficial metabolic effect on the recipient in terms of metabolic parameters such as HOMA-beta and INSindex. This study suggests that islet replacement should be considered for experimental procedures in benign pancreatic conditions.

Cited by 40 publications

References 29 publications

Improved vascular engraftment and function of autotransplanted pancreatic islets as a result of partial pancreatectomy in the mouse and rat

Improved vascular engraftment and function of autotransplanted pancreatic islets as a result of partial pancreatectomy in the mouse and rat

Effective glycemic control achieved by transplanting non-viral cationic liposome-mediated VEGF-transfected islets in streptozotocin-induced diabetic mice

Total Pancreatectomy and Islet Autotransplantation for Chronic Pancreatitis

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