A fibrin gel carrier system for islet transplantation into kidney subcapsule

Lim, Jong Yeon; Min, Bon Hong; Kim, Byoung Geun; Han, Hyun Ju; Kim, Soo Jin; Kim, Chan Wha; Han, Sung Sik; Shin, Juyeon

doi:10.1007/s00592-008-0073-4

Cited by 19 publications

(12 citation statements)

References 11 publications

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“…Of note, we considered retarded glucose control to be a major hurdle for the clinical application of fibrin as an islet vehicle. In the paper published by our colleague [23], fibrinislet composites transplanted underneath the kidney capsule achieved rapid glycemic control with a reduced islet mass. However, we experienced that the same protocol was not effective in the subcutaneous site, whose environment is highly hypoxic due to low vascularization potential (data not shown).…”

Section: Discussionmentioning

confidence: 97%

“…In an in vitro three-dimensional culture system, fibrin glue was demonstrated to facilitate an increase of beta-cell mass while preserving normal function [21]. In preliminary studies, fibrin has been suggested to be a carrier for islet transplantation into the subcutaneous pocket [22,23]. However, major obstacle in the clinical application of fibrin as an islet carrier into the subcutaneous pocket is that there are no optimized protocols of the fibrin-islet composites in vivo to enable the implanted islets to achieve rapid glycemic control with a minimum amount of islets.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

In situ application of hydrogel-type fibrin–islet composite optimized for rapid glycemic control by subcutaneous xenogeneic porcine islet transplantation

Kim

Lim

Nam

et al. 2012

Journal of Controlled Release

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

In situ application of hydrogel-type fibrin–islet composite optimized for rapid glycemic control by subcutaneous xenogeneic porcine islet transplantation

Kim

Lim

Nam

et al. 2012

Journal of Controlled Release

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“…Encapsulating rat islets with fibrin, then transplanting them into diabetic nude mice normalized glycemia with a minimum of only 100 islet equivalents. 52 Another study found that transplantation of islets in a fibrin glue reduced diabetic mouse blood glucose to normal levels. 30 Our results show that human fetal pancreatic cells can be cultured with fibrin and transplanted to yield a successful graft.…”

Section: Discussionmentioning

confidence: 99%

Fibrin supports human fetal islet-epithelial cell differentiation via p70s6k and promotes vascular formation during transplantation

Riopel

Trinder

et al. 2015

Laboratory Investigation

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The human fetal pancreas expresses a variety of extracellular matrix (ECM) binding receptors known as integrins. A provisional ECM protein found in blood clots that can bind to integrin receptors and promote β cell function and survival is fibrin. However, its role in support of human fetal pancreatic cells is unknown. We investigated how fibrin promotes human fetal pancreatic cell differentiation in vitro and in vivo. Human fetal pancreata were collected from 15 to 21 weeks of gestation and collagenase digested. Cells were then plated on tissue-culture polystyrene, or with 2D or 3D fibrin gels up to 2 weeks, or subcutaneously transplanted in 3D fibrin gels. The human fetal pancreas contained rich ECM proteins and expressed integrin αVβ3. Fibrin-cultured human fetal pancreatic cells had significantly increased expression of PDX-1, glucagon, insulin, and VEGF-A, along with increased integrin αVβ3 and phosphorylated FAK and p70 s6k . Fibrin-cultured cells treated with rapamycin, the mTOR pathway inhibitor, had significantly decreased phospho-p70 s6k and PDX-1 expression. Transplanting fibrin-mixed cells into nude mice improved vascularization compared with collagen controls. These results suggest that fibrin supports islet cell differentiation via p70 s6k and promotes vascularization in human fetal islet-epithelial clusters in vivo. Islet transplantation for the treatment of diabetes is currently limited by a shortage of available donor pancreata. 1 To surpass this problem, generating β cells from progenitor cell sources is a viable option. 2 However, this procedure and others like it produce low numbers of effective, functional β cells. 2 A greater understanding of the factors, especially those in the microenvironment, that regulate pancreatic development and islet cell differentiation is required to significantly increase the yield of β cells that these procedures generate for islet transplantation.Human pancreatic development begins at day 26 post conception, with tubular structures protruding from the ventral and dorsal side of the foregut endoderm. Two transcription factors that are required for the initiation of pancreatic development are PTF-1A and PDX-1, 3 in which the latter also promotes β cell maturation and function. 4 By 8 weeks of age, SOX9 is expressed in the pool of pancreatic progenitors 5 and is essential to support their proliferation and survival as well as maintain a transcriptional network with other factors. 6 SOX9 is also an important regulator of pancreatic endocrine cell differentiation. 5 Insulin positivity emerges around 7.5 weeks post conception, followed by glucagon and somatostatin 1 week later. 7 Islet-like structures eventually form where cells commonly express more than one hormone. 7 Subsequently, clustering occurs leading to construction of the islet of Langerhans. 8,9 Cell receptors in the human fetal pancreas that allow interactions with the extracellular environment (ECM) are integrins. Integrins are a family of highly expressed heterodimeric α and β receptors that bind to mo...

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“…136 Subcutaneous transplantation of fibrin-embedded islets was as effective as transplantation of free-floating islets under the kidney capsule in diabetic mice. 137 This study's results further support the notion that fibrin is an effective carrier.…”

Section: Fibrin Support Of Islet Cell Function Survival and Vasculatmentioning

confidence: 99%

Fibrin, a Scaffold Material for Islet Transplantation and Pancreatic Endocrine Tissue Engineering

Riopel

Trinder

Wang

2015

Tissue Engineering Part B: Reviews

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Fibrin is derived from fibrinogen during injury to produce a blood clot and thus promote wound repair. Composed of different domains, including Arg-Gly-Asp amino acid motifs, fibrin is used extensively as a hydrogel and sealant in the clinic. By binding to cell surface receptors like integrins and acting as a supportive 3D scaffold, fibrin has been useful in promoting cell differentiation, proliferation, function, and survival. In particular, fibrin has been able to maintain islet cell architecture, promote beta cell insulin secretion, and islet angiogenesis, as well as inducing a protective effect against cell death. During islet transplantation, fibrin improved neovascularization and islet function. These improvements resulted in reduced number of transplanted islets necessary to reverse diabetes. Therefore, fibrin, as a biocompatible and biodegradable scaffold, should be considered during subcutaneous islet transplantation and beta cell expansion in vitro to ensure maintenance of islet cell function, proliferation, and survival to develop effective cell-based therapies for the treatment of diabetes.

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A fibrin gel carrier system for islet transplantation into kidney subcapsule

Cited by 19 publications

References 11 publications

In situ application of hydrogel-type fibrin–islet composite optimized for rapid glycemic control by subcutaneous xenogeneic porcine islet transplantation

In situ application of hydrogel-type fibrin–islet composite optimized for rapid glycemic control by subcutaneous xenogeneic porcine islet transplantation

Fibrin supports human fetal islet-epithelial cell differentiation via p70s6k and promotes vascular formation during transplantation

Fibrin, a Scaffold Material for Islet Transplantation and Pancreatic Endocrine Tissue Engineering

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