Causes of limited survival of microencapsulated pancreatic islet grafts

Groot, Martijn de; Schuurs, Theo A.; Schilfgaarde, R. van

doi:10.1016/j.jss.2004.02.018

Cited by 160 publications

(126 citation statements)

References 91 publications

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“…The location of the load inside a capsule is crucial for success of transplantation therapies (de Groot et al 2004) since a peripheral position may trigger an immune response from the host. To our knowledge, no previous approach offers a non-invasive analysis of loads in three-dimensional space similar to trajectory analysis.…”

Section: Discussionmentioning

confidence: 99%

A new validation method for clinical grade micro-encapsulation: quantitative high speed video analysis of alginate capsule

et al. 2013

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Micro-encapsulation of cells or tissues is a promising treatment for hormone deficiency diseases (diabetes mellitus, hypoparathyroidism etc.). Alginate, a polymer from marine brown algae, is excellent for encapsulation. Its hydrated structure keeps out large antibodies and immune system cells while allowing diffusion of nutrients and therapeutic factors. Alginate droplets, containing cells, are crosslinked to form stable spherical hydrogel capsules. The position of grafts within the capsule, which decisively affects vulnerability to the host's immune response, has previously not been investigated during the process of crosslinking. We describe for the first time quantitative, high speed video analysis of two perpendicular projections of capsule shape and load during crosslinking. This gives characteristic ''deformation plots'' of the capsule and fully resolved ''trajectories plots'' of capsule load movement. We identify four stages of capsule formation, giving insights into physico-chemical processes involved. Further, we show that mechanical stress on the load can be deduced by measurement of the capsule's shape.

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Section: Discussionmentioning

confidence: 99%

A new validation method for clinical grade micro-encapsulation: quantitative high speed video analysis of alginate capsule

et al. 2013

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“…For example, transplantation into the peritoneum exacerbates hypoxic conditions because oxygen is carried through the peritoneal cavity by passive diffusion only. 81 This passive transport also limits the rate of insulin delivery from the islets, which hampers insulin secretory responses. 81 The result is that 200% to 400% more islets must be implanted when the peritoneum is used as the transplant site.…”

Section: Transplantation Sitementioning

confidence: 99%

“…81 This passive transport also limits the rate of insulin delivery from the islets, which hampers insulin secretory responses. 81 The result is that 200% to 400% more islets must be implanted when the peritoneum is used as the transplant site. 82 Additionally, the peritoneum site is proinflammatory for implantation of alginate-encapsulated pig islets, whereas kidney subcapsular and subcutaneous spaces ISLET ENCAPSULATION 593 improve biocompatibility and islet viability.…”

Section: Transplantation Sitementioning

confidence: 99%

“…It has been shown that chemotaxis alone (without the involvement of hypoxia or biocompatibility) can lead to damage of the encapsulated islets. 81 Chemoattractants, such as cytokines, can activate macrophages, which in turn produce nitric oxide. 94,95 Nitric oxide is small enough to diffuse through the immuno-barrier and damage the islet cells.…”

Section: Immuno-protection Propertiesmentioning

confidence: 99%

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Islet Encapsulation: Strategies to Enhance Islet Cell Functions

et al. 2007

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Diabetes is one of the most prevalent, costly, and debilitating diseases in the world. Although traditional insulin therapy has alleviated the short-term effects, long-term complications are ubiquitous and harmful. For these reasons, alternative treatment options are being developed. This review investigates one appealing area: cell replacement using encapsulated islets. Encapsulation materials, encapsulation methods, and cell sources are presented and discussed. In addition, the major factors that currently limit cell viability and functionality are reviewed, and strategies to overcome these limitations are examined. This review is designed to introduce the reader to cell replacement therapy and cell and tissue encapsulation, especially as it applies to diabetes.

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“…Encapsulation can physically isolate a cell mass from an outside environment and protect the encapsulated cells from contact and attack by immune cells and immunoglobulins. At the same time, the permeability of the capsule membranes allows for accessibility to small molecules such as glucose, insulin, and other molecules that are essential for cell survival (Calafiore et al 1997, de Groot et al 2004, Zimmermann et al 2005.…”

Section: Introductionmentioning

confidence: 99%

Correction of Hyperglycemia in Type 1 Diabetic Models by Transplantation of Encapsulated Insulin-producing Cells Derived from Mouse Embryo Progenitor

Shao¹,

Gao²,

Xie³

et al. 2011

Journal of Endocrinology

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Shortage of cadaveric pancreata and requirement of immune suppression are two major obstacles in transplantation therapy of type 1 diabetes. Here, we investigate whether i.p. transplantation of alginate-encapsulated insulin-producing cells from the embryo-derived mouse embryo progenitorderived insulin-producing-1 (MEPI-1) line could lower hyperglycemia in immune-competent, allogeneic diabetic mice. Within days after transplantation, hyperglycemia was reversed followed by about 2 . 5 months of normo-to moderate hypoglycemia before relapsing. Mice transplanted with unencapsulated MEPI cells relapsed within 2 weeks. Removal of the transplanted capsules by washing of the peritoneal cavity caused an immediate relapse of hyperglycemia that could be reversed with a second transplantation. The removed capsules had fibrotic overgrowth but remained permeable to 70 kDa dextrans and displayed glucose-stimulated insulin secretion.Following transplantation, the number of cells in capsules increased initially, before decreasing to below the starting cell number at 75 days. Histological examination showed that beyond day 40 post-transplantation, encapsulated cell clusters exhibited proliferating cells with a necrotic core. Blood glucose, insulin levels, and oral glucose tolerance test in the transplanted animals correlated directly with the number of viable cells remaining in the capsules. Our study demonstrated that encapsulation could effectively protect MEPI cells from the host immune system without compromising their ability to correct hyperglycemia in immune-competent diabetic mice for 2 . 5 months, thereby providing proof that immunoisolation of expansible but immune-incompatible stem cell-derived surrogate b-cells by encapsulation is a viable diabetes therapy.

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Causes of limited survival of microencapsulated pancreatic islet grafts

Cited by 160 publications

References 91 publications

A new validation method for clinical grade micro-encapsulation: quantitative high speed video analysis of alginate capsule

A new validation method for clinical grade micro-encapsulation: quantitative high speed video analysis of alginate capsule

Islet Encapsulation: Strategies to Enhance Islet Cell Functions

Correction of Hyperglycemia in Type 1 Diabetic Models by Transplantation of Encapsulated Insulin-producing Cells Derived from Mouse Embryo Progenitor

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