Dataset Information

Effects of Composition of Alginate-Polyethylene Glycol Microcapsules and Transplant Site on Encapsulated Islet Graft Outcomes in Mice.

ABSTRACT:

Background

Understanding the effects of capsule composition and transplantation site on graft outcomes of encapsulated islets will aid in the development of more effective strategies for islet transplantation without immunosuppression.

Methods

Here, we evaluated the effects of transplanting alginate (ALG)-based microcapsules (Micro) in the confined and well-vascularized epididymal fat pad (EFP) site, a model of the human omentum, as opposed to free-floating in the intraperitoneal cavity (IP) in mice. We also examined the effects of reinforcing ALG with polyethylene glycol (PEG). To allow transplantation in the EFP site, we minimized capsule size to 500 ± 17 ?m. Unlike ALG, PEG resists osmotic stress, hence we generated hybrid microcapsules by mixing PEG and ALG (MicroMix) or by coating ALG capsules with a 15 ± 2 ?m PEG layer (Double).

Results

We found improved engraftment of fully allogeneic BALB/c islets in Micro capsules transplanted in the EFP (median reversal time [MRT], 1 day) versus the IP site (MRT, 5 days; P < 0.01) in diabetic C57BL/6 mice and of Micro encapsulated (MRT, 8 days) versus naked (MRT, 36 days; P < 0.01) baboon islets transplanted in the EFP site. Although in vitro viability and functionality of islets within MicroMix and Double capsules were comparable to Micro, addition of PEG to ALG in MicroMix capsules improved engraftment of allogeneic islets in the IP site, but resulted deleterious in the EFP site, probably due to lower biocompatibility.

Conclusions

Our results suggest that capsule composition and transplant site affect graft outcomes through their effects on nutrient availability, capsule stability, and biocompatibility.

SUBMITTER: Villa C

PROVIDER: S-EPMC5642344 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effects of Composition of Alginate-Polyethylene Glycol Microcapsules and Transplant Site on Encapsulated Islet Graft Outcomes in Mice.

Villa Chiara C Manzoli Vita V Abreu Maria M MM Verheyen Connor A CA Seskin Michael M Najjar Mejdi M Molano R Damaris RD Torrente Yvan Y Ricordi Camillo C Tomei Alice A AA

Transplantation 20170501 5

<h4>Background</h4>Understanding the effects of capsule composition and transplantation site on graft outcomes of encapsulated islets will aid in the development of more effective strategies for islet transplantation without immunosuppression.<h4>Methods</h4>Here, we evaluated the effects of transplanting alginate (ALG)-based microcapsules (Micro) in the confined and well-vascularized epididymal fat pad (EFP) site, a model of the human omentum, as opposed to free-floating in the intraperitoneal ...[more]

PMID: 27525644

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Project description:An injection of hydrogel-encapsulated islets that controls blood glucose levels over long term would provide a much needed alternative treatment for type 1 diabetes mellitus (T1DM). To this end, we tested the feasibility of using an injectable polyethylene glycol (PEG) hydrogel as a scaffold for islet encapsulation. Encapsulated islets cultured in vitro for 6 days showed excellent cell viability and released insulin with higher basal and stimulated insulin secretion than control islets. Host responses to PEG hydrogels were studied by injecting PEG hydrogels (no treatment and vehicle controls used) into the peritoneal cavities of B6D2F1 mice and monitoring alterations in body weight, food and water intake, and blood glucose levels. After 2 weeks, peritoneal cavity cells were harvested, followed by hydrogel retrieval, and extraction of spleens. Body weights, food and water intake, and blood glucose levels were unaltered in mice injected with hydrogels compared to no treatment and vehicle-injected control mice. Frozen sections of a hydrogel showed the presence of tissues and small number of immune cells surrounding the hydrogel but no cell infiltration into the hydrogel bulk. Spleen sizes were not significantly different under the experimental conditions. Peritoneal cavity cells were slightly higher in mice injected with hydrogels compared to control mice but no statistical difference between vehicle- and hydrogel-injected mice was noted. As an in vivo feasibility study, streptozotocin-induced diabetic mice were injected with vehicle or hydrogels containing 50 islets each into two sites, the peritoneal cavity and a subcutaneous site on the back. Transient control of blood glucose levels were observed in mice injected with hydrogels containing islets. In summary, we developed an injectable PEG hydrogel that supported islet function and survival in vitro and in vivo and elicited only a mild host response. Our work illustrates the feasibility of using injectable PEG hydrogels for islet encapsulation.

Dataset Information

Effects of Composition of Alginate-Polyethylene Glycol Microcapsules and Transplant Site on Encapsulated Islet Graft Outcomes in Mice.

Background

Methods

Results

Conclusions

Publications

Effects of Composition of Alginate-Polyethylene Glycol Microcapsules and Transplant Site on Encapsulated Islet Graft Outcomes in Mice.

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