Human and Porcine Islet Transplants in a New Double Capsule

Safley, Susan A.; Gordon, Kereen; Barber, Graham F.; Holdcraft, Robert W.; Turgeon, Nicole A.; Larsen, Christian; Gazda, Lawrence S.; Weber, Collin J.

doi:10.1016/j.jss.2012.10.506

Cited by 4 publications

(7 citation statements)

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“…Therefore, we postulated that porcine islet damage and graft failure in the NHPs receiving APIs in single capsules were caused by exposure of islets near the periphery of single capsules or by anti‐porcine and anti‐Gal antibodies, which we had demonstrated could enter Ba‐gelled capsules. As a result of these findings, we developed a double alginate microcapsule that would exclude host IgG and IgM and more adequately cover the islets . We hypothesized that this double capsule would provide longer term functional survival of transplanted islets, because PLL prevents host IgG from accessing the inner, islet‐containing capsule.…”

Section: Resultsmentioning

confidence: 99%

“…We previously tested the efficacy of single‐encapsulated vs double‐encapsulated human and porcine islets in diabetic NOD mice . In non‐immunosuppressed NODs, APIs in single Ba‐gelled alginate capsules functioned for an average of 23 ± 22 days (n = 50) but APIs in double capsules functioned significantly longer, for 47 ± 33 days (n = 22, P = 0.005)].…”

Section: Resultsmentioning

confidence: 99%

“…We previously tested the efficacy of single-encapsulated vs doubleencapsulated human and porcine islets in diabetic NOD mice. 62 In Figure 5A) showing that the remaining functional islet mass was not sufficient to correct diabetes.…”

Section: Function Of Double-encapsulated Apis In Nhps Treated With mentioning

confidence: 99%

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Microencapsulated adult porcine islets transplanted intraperitoneally in streptozotocin‐diabetic non‐human primates

Safley

Kenyon

Berman

et al. 2018

Xenotransplantation

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With donor xenoislet microencapsulation and host immunosuppression, APIs corrected hyperglycemia after ip transplantation in STZ-diabetic NHPs in the short term. The islet xenografts lost efficacy gradually, but at graft failure, some viable islets remained, substantial porcine C-peptide was detected in the peritoneal graft site, and there was very little evidence of a host immune response. We postulate that chronic effects of non-immunologic factors, such as in vivo hypoxic and hyperglycemic conditions, damaged the encapsulated islet xenografts. To achieve long-term function, new approaches must be developed to prevent this damage, for example, by increasing the oxygen supply to microencapsulated islets in the ip space.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Microencapsulated adult porcine islets transplanted intraperitoneally in streptozotocin‐diabetic non‐human primates

Safley

Kenyon

Berman

et al. 2018

Xenotransplantation

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“…Simply tuning the parameters of spherical microencapsulation techniques to produce smaller capsules is therefore not a viable strategy to minimize capsule size. While core-shell structures have been developed which may prevent islet protrusion [305][306][307][308][309], these structures do not address the diffusional problems discussed earlier, nor some challenges related to blood contact.…”

Section: Nanoencapsulationmentioning

confidence: 99%

Nanotechnology in cell replacement therapies for type 1 diabetes

Ernst

Bowers

Wang

et al. 2019

Advanced Drug Delivery Reviews

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Islet transplantation is a promising long-term, compliance-free, complication-preventing treatment for type 1 diabetes. However, islet transplantation is currently limited to a narrow set of patients due to the shortage of donor islets and side effects from immunosuppression. Encapsulating cells in an immunoisolating membrane can allow for their transplantation without the need for immunosuppression. Alternatively, "open" systems may improve islet health and function by allowing vascular ingrowth at clinically attractive sites. Many processes that enable graft success in both approaches occur at the nanoscale level-in this review we thus consider nanotechnology in cell replacement therapies for type 1 diabetes. A variety of biomaterial-based strategies at the nanometer range have emerged to promote immune-isolation or modulation, proangiogenic, or insulinotropic effects. Additionally, coating islets within nano-thin polymer films has burgeoned as an islet protection modality. Materials approaches that utilize nanoscale features manipulate biology at the molecular scale, offering unique solutions to the enduring challenges of islet transplantation.

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“…Parallel evaluation of different encapsulation platforms in the same experimental setting, which could provide critical information to identify strengths and weaknesses to be addressed before clinical testing, has not been performed. Here, we aimed at examining in parallel selected microencapsulation platforms that were previously reported to permit long-term diabetes reversal in preclinical T1D models: single and double capsules (SCs, traditional microencapsulation method, and DCs, improved method for biocompatibility, respectively) made of alginate ( Safley et al, 2013 ; Safley et al, 2018 ; Safley et al, 2020 ) (medium viscosity high guluronic, MVG, or low viscosity high mannuronic acid, LVM) and conformally coated capsules (CCs, improved method for capsule size minimization) made of polyethylene glycol (PEG) ( Tomei et al, 2014 ; Manzoli et al, 2018 ). We determined how the different capsule characteristics affect the functionality of primary human islets (HIs) in vitro (i.e., glucose-stimulated insulin secretion, GSIS) and in vivo (blood glucose monitoring and glucose tolerance test, GTT) in their conventional transplant site (SCs, DCs: peritoneal cavity; CCs: fat pad) compared with non-coated (NC) HIs.…”

Section: Introductionmentioning

confidence: 99%

Parallel Evaluation of Polyethylene Glycol Conformal Coating and Alginate Microencapsulation as Immunoisolation Strategies for Pancreatic Islet Transplantation

Toni

Stock

Devaux

et al. 2022

Front. Bioeng. Biotechnol.

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Pancreatic islet transplantation improves metabolic control and prevents complications in patients with brittle type 1 diabetes (T1D). However, chronic immunosuppression is required to prevent allograft rejection and recurrence of autoimmunity. Islet encapsulation may eliminate the need for immunosuppression. Here, we analyzed in parallel two microencapsulation platforms that provided long-term diabetes reversal in preclinical T1D models, alginate single and double capsules versus polyethylene glycol conformal coating, to identify benefits and weaknesses that could inform the design of future clinical trials with microencapsulated islets. We performed in vitro and in vivo functionality assays with human islets and analyzed the explanted grafts by immunofluorescence. We quantified the size of islets and capsules, measured capsule permeability, and used these data for in silico simulations of islet functionality in COMSOL Multiphysics. We demonstrated that insulin response to glucose stimulation is dependent on capsule size, and the presence of permselective materials augments delays in insulin secretion. Non-coated and conformally coated islets could be transplanted into the fat pad of diabetic mice, resulting in comparable functionality and metabolic control. Mac-2+ cells were found in conformally coated grafts, indicating possible host reactivity. Due to their larger volume, alginate capsules were transplanted in the peritoneal cavity. Despite achieving diabetes reversal, changes in islet composition were found in retrieved capsules, and recipient mice experienced hypoglycemia indicative of hyperinsulinemia induced by glucose retention in large capsules as the in silico model predicted. We concluded that minimal capsule size is critical for physiological insulin secretion, and anti-inflammatory modulation may be beneficial for small conformal capsules.

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Human and Porcine Islet Transplants in a New Double Capsule

Cited by 4 publications

References 0 publications

Microencapsulated adult porcine islets transplanted intraperitoneally in streptozotocin‐diabetic non‐human primates

Microencapsulated adult porcine islets transplanted intraperitoneally in streptozotocin‐diabetic non‐human primates

Nanotechnology in cell replacement therapies for type 1 diabetes

Parallel Evaluation of Polyethylene Glycol Conformal Coating and Alginate Microencapsulation as Immunoisolation Strategies for Pancreatic Islet Transplantation

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