Indefinite islet protection from autoimmune destruction in nonobese diabetic mice by agarose microencapsulation without immunosuppression1

Kobayashi, T; Aomatsu, Yukio; Iwata, Hiroo; Kin, Tatsuya; Kanehiro, Hiromichi; Hisanaga, Michiyoshi; Ko, Saiho; Nagao, Mitsuo; Nakajima, Yoshiyuki

doi:10.1097/01.tp.0000053749.36365.7e

Cited by 97 publications

(52 citation statements)

References 28 publications

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“…When islet-containing droplets of sodium alginate solution are extruded from a needle and dropped into a divalent cation bath, they gel instantaneously, allowing the formed calcium alginate beads to retain the perfectly spherical shape that the alginate droplet had upon extrusion. Although the suitability of other polymers is still under investigation (e.g., agarose 20,21 ), none has been as extensively studied nor has reached the same level of performance as alginate. As a natural polymer, alginate is limited by its tendency to be largely contaminated.…”

Section: Introductionmentioning

confidence: 98%

Evaluation of alginate purification methods: Effect on polyphenol, endotoxin, and protein contamination

Dusseault

Tam

Ménard

et al. 2005

J Biomedical Materials Res

140

106

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Alginate, a polysaccharide extracted from brown seaweed, is widely used for the microencapsulation of islets of Langerhans, allowing their transplantation without immunosuppression. This natural polymer is known to be largely contaminated. The implantation of islets encapsulated using unpurified alginate leads to the development of fibrotic cell overgrowth around the microcapsules and normalization of the blood glucose is restricted to a very short period if it is achieved at all. Several research groups have developed their own purification method and obtained relatively good results. No comparative evaluation of the efficiencies of these methods has been published. We conducted an evaluative study of five different alginate preparations: a pharmaceutical-grade alginate in its raw state, the same alginate after purification according to three different published methods, and a commercially available purified alginate. The results showed that all purification methods reduced the amounts of known contaminants, that is, polyphenols, endotoxins, and proteins, although with varying efficiencies. Increased viscosity of alginate solutions was observed after purification of the alginates. Despite a general efficiency in decreasing contamination levels, all of the purified alginates contained relatively high residual amounts of protein contaminants. Because proteins may be immunogenic, these residual proteins may have a role in persisting microcapsule immunogenicity.

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Section: Introductionmentioning

confidence: 98%

Evaluation of alginate purification methods: Effect on polyphenol, endotoxin, and protein contamination

Dusseault

Tam

Ménard

et al. 2005

J Biomedical Materials Res

140

106

View full text Add to dashboard Cite

show abstract

“…Currently, there are a number of achievements in encapsulating islets seen in small and large animal studies, as well as in early phase clinical trials. A syngeneic transplant of nonobese diabetic (NOD) into prediabetic islets diabetic NOD recipients, using 5% agarose encapsulating 1500-2000 islet equivalents (IEq), showed that intraperitoneal implantation as well as omental pouch transplants demonstrated prolonged euglycemia for a period of 100 days compared to 8 days for unencapsulated islet transplants [13]. This study was repeated in 2006, where the same period of normoglycemia was observed in transplant recipients.…”

Section: History Of Animal and Human Trials Of Islet Encapsulationmentioning

confidence: 87%

Avoiding Immunosuppression for Islet Transplantation: Use of Protective Biomaterials

Alexander¹,

Nguyen²,

Flores³

et al. 2017

Challenges in Pancreatic Pathology

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Islet transplantation, with the advent of the Edmonton protocol in 2000, has offered a significant alternative for long-lasting treatment of type 1 diabetes. However, the immunosuppression required for transplantation has the cytotoxic effect on pancreatic islets, and thus limiting the long-term efficacy of the transplant. Immediate loss of islets after transplant was also observed because of immediate blood-mediated inflammatory response (IBMIR), which kills islets transplanted in the liver through portal vein. There is also commonly a lack of microvascular blood supply to the transplanted islets. In this chapter, we will review the variety of technologies used to protect transplanted islets against toxicity of immunosuppression, immune rejection, and inflammatory response. We will evaluate the mechanisms of these technologies and their progress in solving the challenges to islet transplantation. The technologies include encapsulation of transplanted islets in various polymers, transplants in sites other than the liver, and creation of new prevascularized transplant site. These technologies offer several mechanisms to prevent immune rejection or immediate contact with cytotoxic inflammatory response, in addition to maintaining islet integrity. New transplant sites are also being developed to support the islets, by allowing establishment of microvasculature and innervation, prior to addition of the islets.

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“…Åêñïåðèìåíòàëüíà àïðî-áàö³ÿ îòðèìàíèõ ðåçóëüòàò³â êóëüòèâóâàííÿ ñâ³ä-÷èòü ïðî ¿õ äîñèòü âèñîêó åôåêòèâí³ñòü [77][78][79][80][81].…”

Section: комбінована ксенотрансплантація як метод пролонгації життєздunclassified

Combined xenotransplantation as a method of prolonging the viability and function of the graft in the treatment of various forms of hypocorticism

Ларін¹,

Анастасій²,

Гирявенко³

et al. 2013

CE&ES

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Indefinite islet protection from autoimmune destruction in nonobese diabetic mice by agarose microencapsulation without immunosuppression1

Abstract: Agarose microcapsules were able to completely protect NOD islet isografts from autoimmune destruction in the syngeneic islet transplantation model.

Cited by 97 publications

References 28 publications

Evaluation of alginate purification methods: Effect on polyphenol, endotoxin, and protein contamination

Evaluation of alginate purification methods: Effect on polyphenol, endotoxin, and protein contamination

Avoiding Immunosuppression for Islet Transplantation: Use of Protective Biomaterials

Combined xenotransplantation as a method of prolonging the viability and function of the graft in the treatment of various forms of hypocorticism

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