Clinical islet transplant—state of the art

Shapiro, A. M. James; Ryan, E. A.; Lakey, Jonathan R. T.

doi:10.1016/s0041-1345(01)02416-2

Cited by 26 publications

(10 citation statements)

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“…Pancreatic islet transplantation is a promising treatment for patients with Type 1 diabetes mellitus, which results in hyperglycemia due to islet β cells damage [1][2][3][4]. However, maintaining the structural integrity and insulin release of post-isolated human islets is a pre-requisite for achieving successful islet transplantation.…”

Section: Introductionmentioning

confidence: 99%

Bone marrow increases human islets insulin positive cells in co-culture: quantification with flow cytometry

Wang¹,

Xiong²,

Hassani³

et al. 2011

JDM

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We have previously demonstrated that allogeneic human bone marrow (BM) supports human islet function and longevity in vitro. We hypothesize that BM supporting human islets may include to increase β-cell in cultured islets. In this study, we developed a method to quantify insulin-producing β cells from cultured islets by using immunofluorescent staining and flow cytometry analysis to explore this possibility. The results show that human islets cocultured with BM for 39 days contained a significantly higher number of insulin-positive β cells (42.3% ± 4.5%) compared to the islet-only cultures (1.15% ± 0.78%), and increased insulin release levels evaluated by ELISA is consistent with increased β cells in same culture condition. Human islet culture with BM significantly increase β-cells while islet only culture lost β-cells in same culture period supports the possibility of BM increasing β-cells in cultured islets.

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Section: Introductionmentioning

confidence: 99%

Bone marrow increases human islets insulin positive cells in co-culture: quantification with flow cytometry

Wang¹,

Xiong²,

Hassani³

et al. 2011

JDM

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“…A major challenge in developing a cell-based therapy for insulin-dependent diabetes consists of ensuring an appropriate cell source. Recent clinical studies treating diabetes in humans by transplantation of allogeneic islets have received significant attention (Shapiro et al, 2000(Shapiro et al, , 2001a(Shapiro et al, , 2001b. However, the problems of limited tissue availability and of side effects of long-term immunosuppression remain as substantial obstacles in such a therapeutic approach.…”

Section: Discussionmentioning

confidence: 99%

Hybrid pancreatic tissue substitute consisting of recombinant insulin‐secreting cells and glucose‐responsive material

Gross

Sambanis

2004

Biotech & Bioengineering

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Insulin-dependent diabetes is a serious pathological condition, currently treated by blood glucose monitoring and daily insulin injections, which, however, do not prevent long-term complications. A tissue-engineered pancreatic substitute has the potential to provide a more physiologic, less invasive, and potentially less costly treatment of the disease. A major issue in developing such a substitute is the cells being used. Nonpancreatic cells, retrieved from the same patient and genetically engineered to secrete insulin constitutively or with some glucose responsiveness, offer the significant advantages of being immune-acceptable and relaxing the tissue availability limitations, which exist with islets from cadaveric donors. These cells, however, do not have insulin secretion dynamics appropriate for restoration of euglycemia in higher animals and, eventually, humans. In this study, we present the concept of a hybrid pancreatic substitute consisting of such cells sequestered in a material exhibiting glucose-dependent changes of its permeability to insulin. A Concanavalin A-glycogen material sandwiched between two polycarbonate membranes and exhibiting glucose-dependent sol-gel transformations was used. Rates of insulin transport through this material in gel and sol forms were characterized for both FITC-labeled insulin in solution and insulin secreted by betaTC3 mouse insulinoma cells. Effective diffusivities through sol were found to be up to 3.5-fold higher than through the gel state of the material. A mathematical model of a hybrid construct was formulated and analyzed to simulate the secretory behavior in response to step ups and downs in the surrounding glucose concentration. The experimental and modeling studies indicate that a hybrid pancreatic substitute consisting of constitutively secreting cells and glucose-responsive material has the potential to provide a more physiologic regulation of insulin release than the cells by themselves or in an inert material.

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“…26,27 Also, thrombomodulin (TM) could improve early outcomes after intraportal islet transplantation via complex with thrombin in blood. 28 However, systemic administration of anticoagulants will always be associated with an increased risk of bleeding, which is particularly important in islet transplantation due to transhepatic puncture of a large portal vein. Therefore, for successful intrahepatic islet transplantation, islet PEGylation remedy could be a good protocol to prevent IBMIR without any anticoagulant administration.…”

Section: Surface Modification With Peg Onto Islet Surfacementioning

confidence: 99%

Islet surface PEGylation attenuate the instant blood-mediated inflammatory reaction in intrahepatic islet transplantation

Lee

2011

Macromol. Res.

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Clinically intrahepatic pancreatic islet transplantation is carried out for patients suffering from type 1 diabetes mellitus but the instant blood mediated inflammatory reaction (IBMIR) initiated from platelet adhesion onto the islet can impair the islet function. Previously, chemically modified islets were developed with a protective poly(ethylene glycol) (PEG) polymer, which could repel adhering platelets in the blood stream owing to its biocompatible properties. The results show that PEG-based chemical modification can prevent the adhesion of platelets in the tubing loop model in vitro. Moreover, this islet PEGylation strategy appears to avoid the islet cytotoxicity associated with the further recruitment of leukocytes and monocytes via an interaction with platelets, thereby showing normal viability and function of insulin secretion of the PEGylated islets. In addition, when transplanted into the liver via the portal vein, the PEGylated islets could still normally function for insulin secretion without binding onto the islet surface with platelets and/or leukocytes. On the other hand, the surface of unmodified islets (control) was bound severely with platelets and leukocytes in vitro and in vivo, thereby affecting the viability and functionality of the islets. These results strongly suggest that an islet PEGylation remedy can provide an effective clinical means of attenuating IBMIR after intrahepatic islet transplantation.

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Clinical islet transplant—state of the art

Cited by 26 publications

References 0 publications

Bone marrow increases human islets insulin positive cells in co-culture: quantification with flow cytometry

Bone marrow increases human islets insulin positive cells in co-culture: quantification with flow cytometry

Hybrid pancreatic tissue substitute consisting of recombinant insulin‐secreting cells and glucose‐responsive material

Islet surface PEGylation attenuate the instant blood-mediated inflammatory reaction in intrahepatic islet transplantation

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