Quantitative Assessment of Islets of Langerhans Encapsulated in Alginate

Johnson, Amy S.; O'Sullivan, Esther S.; D'Aoust, Laura; Omer, Abdulkadir; Bonner-Weir, Susan; Fisher, Robert J.; Weir, Gordon C.; Colton, Clark K.

doi:10.1089/ten.tec.2009.0510

Cited by 63 publications

(43 citation statements)

References 63 publications

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“…It has been repeatedly shown that native pancreatic islets have a disproportionately high level of vascularization (13)(14)(15)(16)(17)(18). During the process of islet isolation their vasculature is disrupted, and after transplantation the islets depend on oxygen diffusion from tissue surrounding the transplantation site until revascularization has occurred.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of human islets without immunosuppression

Ludwig

Reichel

Steffen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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258

198

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Transplantation of pancreatic islets is emerging as a successful treatment for type-1 diabetes. Its current stringent restriction to patients with critical metabolic lability is justified by the long-term need for immunosuppression and a persistent shortage of donor organs. We developed an oxygenated chamber system composed of immune-isolating alginate and polymembrane covers that allows for survival and function of islets without immunosuppression. A patient with type-1 diabetes received a transplanted chamber and was followed for 10 mo. Persistent graft function in this chamber system was demonstrated, with regulated insulin secretion and preservation of islet morphology and function without any immunosuppressive therapy. This approach may allow for future widespread application of cell-based therapies.β-cell replacement | immune barrier | oxygenation T he transplantation of isolated islets of Langerhans has evolved into a successful method to restore endogenous insulin secretion and stabilize glycemic control without the risk of hypoglycemia (1, 2). However, due to persistent lack of human donor pancreata and the requirement of chronic immune suppression to prevent graft rejection through allo-and autoimmunity, the indication for islet transplantation is restricted to patients with complete insulin deficiency, critical metabolic lability, and repeated severe hypoglycemia despite optimal diabetes management and compliance (3). Furthermore, progressive loss of islet function over time due to chronic hypoxia and inflammatory processes at the intraportal transplantation site remain additional unresolved challenges in islet transplantation (4, 5).When islets are immune-isolated, the lack of oxygen impairs the survival and long-term function of the cells. Experimental approaches to overcome this impediment have involved the implantation of hypoxia-resistant islets, stimulation and sprouting of vessels, and the use of islets designed to contain an intracellular oxygen carrier as well as local oxygen production by electrochemical processes or photosynthesis (6). However, so far, none of these methods have been capable of guaranteeing an adequate physiological oxygen concentration or to allow, at the same time, an adequate immunoprotective environment. To overcome these major obstacles, we have developed a strategy for islet macroencapsulation that provides sufficient immune isolation and permits endogenously regulated islet graft function. Here we demonstrate a system that allows a controlled oxygen supply to the islet graft by means of an integrated oxygen reservoir that can be refilled regularly and can maintain oxygen pressure. Earlier we demonstrated that a sufficient supply of oxygen for maintaining optimal islet function can simultaneously ensure functional potency and immunoprotective characteristics of the device. After application of this bioartificial pancreas system in allogeneic and xenogeneic preclinical diabetes models (7-9) the method was then applied to allogeneic human islet transplantation in an ind...

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Section: Discussionmentioning

confidence: 99%

Transplantation of human islets without immunosuppression

Ludwig

Reichel

Steffen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

258

198

View full text Add to dashboard Cite

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“…For short‐term (acute) hypoxia in vitro, no difference on viability or function was seen for encapsulated versus nonencapsulated human islets . However, culture of encapsulated islets under low oxygen conditions shows loss of viable tissue and necrotic cores . To counteract the lowering of oxygen tension, perfluorocarbon emulsion and CaO 2 have been suggested as coencapsulated sources of oxygen.…”

Section: The Inner Life Of the Capsule—oxygen Supply And Microenvironmentioning

confidence: 99%

Current and Future Perspectives on Alginate Encapsulated Pancreatic Islet

Strand

Coron

Skjåk‐Bræk

2017

Stem Cells Translational Medicine

101

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Transplantation of pancreatic islets in immune protective capsules holds the promise as a functional cure for type 1 diabetes, also about 40 years after the first proof of principal study. The concept is simple in using semipermeable capsules that allow the ingress of oxygen and nutrients, but limit the access of the immune system. Encapsulated human islets have been evaluated in four small clinical trials where the procedure has been evaluated as safe, but lacking long‐term efficacy. Host reactions toward the biomaterials used in the capsules may be one parameter limiting the long‐term function of the graft in humans. The present article briefly discusses important capsule properties such as stability, permeability and biocompatibility, as well as possible strategies to overcome current challenges. Also, recent progress in capsule development as well as the production of insulin‐producing cells from human stem cells that gives promising perspectives for the transplantation of encapsulated insulin‐producing tissue is briefly discussed. Stem Cells Translational Medicine 2017;6:1053–1058

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“…Enhanced solubility will lead to enhanced permeability because the permeability is the product of the gas solubility and diffusivity in the material of interest. We have currently been studying a perfluorocarbon emulsion madefrom perfluorodecalin and 20 wt% (w/v) Intralipid Ò (Baxter), a soybean oil emulsion [59]. To assess the benefits of PFC-containing microcapsules, a theoretical model has been developed to predict the local partial pressure of oxygen, which, in turn, is used to assess tissue viability and the fraction of normal insulin secretion for encapsulated islets and single cells.…”

Section: Theoretical Analysis Of Pfc-containing Microcapsulesmentioning

confidence: 99%