Xenotransplantation of tannic acid‐encapsulated neonatal porcine islets decreases proinflammatory innate immune responses

Barra, Jessie M.; Kozlovskaya, Veronika; Kepple, Jessica D.; Seeberger, Karen; Kuppan, Purushothaman; Hunter, Chad S.; Korbutt, Gregory S.; Kharlampieva, Eugenia; Tse, Hubert M.

doi:10.1111/xen.12706

Cited by 11 publications

(11 citation statements)

References 71 publications

(92 reference statements)

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“…These approaches include induction of localized immunosuppression by encapsulating islets with antioxidant-containing nanothin coatings to decrease oxidative stress ( 46 ), incorporating dexamethasone-eluting micelles to suppress inflammatory responses ( 47 ) or by cotransplanting BAT-derived MSCs to further induce Treg differentiation ( 42 ). Additionally, BAT is a promising extrahepatic transplant site for other sources of insulin-producing β cells such as stem cell-derived β cells ( 48 – 51 ) or genetically modified xenogeneic porcine islets ( 52 – 57 ), both of which have demonstrated promise. However, the maximum possible islet number for a single BAT depot would have to be defined in both these preclinical models and also in human BAT to determine if the higher number of islet equivalents needed in these alternative approaches would be feasible.…”

Section: Discussionmentioning

confidence: 99%

Islet transplantation into brown adipose tissue can delay immune rejection

Kepple¹,

Barra²,

Young³

et al. 2022

JCI Insight

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Type 1 diabetes is an autoimmune disease characterized by insulin-producing beta-cell destruction. While islet transplantation restores euglycemia and improves patient outcomes, an ideal transplant site remains elusive. Brown adipose tissue (BAT) is a highly vascularized and anti-inflammatory microenvironment. As these tissue features can promote islet graft survival, we hypothesize that islets transplanted into BAT will maintain islet graft and BAT function, while delaying immune-mediated rejection. We performed syngeneic and allogeneic islet transplants into BAT or under the kidney capsule of streptozotocin (STZ)-induced diabetic NOD.Rag and NOD mice to investigate islet graft function, BAT function, metabolism, and immune-mediated rejection. Islet grafts within BAT restored euglycemia similarly to kidney capsule controls. Islets transplanted in BAT maintained expression of islet hormones, transcription factors, and were vascularized.Compared to kidney capsule and euglycemic mock surgery controls, no differences in glucose or insulin tolerance, thermogenic regulation, or energy expenditure were observed with islet grafts in BAT. Immune profiling of BAT revealed enriched antiinflammatory macrophages and T cells. Compared to kidney capsule, islets transplanted in BAT demonstrated significant delays in autoimmune and allograft rejection, possibly due to increased anti-inflammatory immune populations. Our data support BAT as an alternative islet transplantation site that may improve graft survival.

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Section: Discussionmentioning

confidence: 99%

Islet transplantation into brown adipose tissue can delay immune rejection

Kepple¹,

Barra²,

Young³

et al. 2022

JCI Insight

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“…By using TA, antioxidants and neutral polymer poly(n-vinylpyrrolidone) (PVPON) multilayers to form a nano-thin encapsulation material PVPON/TA. After xenografting, PVPON/TA-encapsulated neonatal porcine islets were not defective in glucose responsiveness and had reduced expression of MHC-II and co-stimulatory molecules CD40, CD80 and CD86 in antigen-presenting cells ( 129 ).…”

Section: Anti-inflammatory Hydrogelsmentioning

confidence: 99%

Islet Encapsulation: New Developments for the Treatment of Type 1 Diabetes

Zhang

Gonelle‐Gispert

et al. 2022

Front. Immunol.

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Islet transplantation is a promising approach for the treatment of type 1 diabetes (T1D). Currently, clinical islet transplantation is limited by allo - and autoimmunity that may cause partial or complete loss of islet function within a short period of time, and long-term immunosuppression is required to prevent rejection. Encapsulation into semipermeable biomaterials provides a strategy that allows nutrients, oxygen and secreted hormones to diffuse through the membrane while blocking immune cells and the like out of the capsule, allowing long-term graft survival and avoiding long-term use of immunosuppression. In recent years, a variety of engineering strategies have been developed to improve the composition and properties of encapsulation materials and to explore the clinical practicality of islet cell transplantation from different sources. In particular, the encapsulation of porcine islet and the co-encapsulation of islet cells with other by-standing cells or active ingredients for promoting long-term functionality, attracted significant research efforts. Hydrogels have been widely used for cell encapsulation as well as other therapeutic applications including tissue engineering, cell carriers or drug delivery. Here, we review the current status of various hydrogel biomaterials, natural and synthetic, with particular focus on islet transplantation applications. Natural hydrophilic polymers include polysaccharides (starch, cellulose, alginic acid, hyaluronic acid, chitosan) and peptides (collagen, poly-L-lysine, poly-L-glutamic acid). Synthetic hydrophilic polymers include alcohol, acrylic acid and their derivatives [poly (acrylic acid), poly (methacrylic acid), poly(acrylamide)]. By understanding the advantages and disadvantages of materials from different sources and types, appropriate materials and encapsuling methods can be designed and selected as needed to improve the efficacy and duration of islet. Islet capsule transplantation is emerging as a promising future treatment for T1D.

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“…1,2,7,16,17,22,24,25 Several studies have shown that subcutaneous transplantation sites can be modified to promote neovascularization posttransplantation. These methods involve the use of biologics such as growth factors (beta-fibroblast growth factor [FGF], vascular endothelial growth factor), [26][27][28] chemical modifications of the encapsulation material, 29 anti-inflammatory drugs, 14,30,31 co-delivery of mesenchymal stem cells, [32][33][34] and the use of oxygen generators, 10,[35][36][37] among others.…”

Section: Introductionmentioning

confidence: 99%

Replenishable prevascularized cell encapsulation devices increase graft survival and function in the subcutaneous space

Chendke

Kharbikar

Ashe

et al. 2023

Bioengineering & Transla Med

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Beta cell replacement therapy (BCRT) for patients with type 1 diabetes (T1D) improves blood glucose regulation by replenishing the endogenous beta cells destroyed by autoimmune attack. Several limitations, including immune isolation, prevent this therapy from reaching its full potential. Cell encapsulation devices used for BCRT provide a protective physical barrier for insulin-producing beta cells, thereby protecting transplanted cells from immune attack. However, poor device engraftment posttransplantation leads to nutrient deprivation and hypoxia, causing metabolic strain on transplanted beta cells. Prevascularization of encapsulation devices at the transplantation site can help establish a host vascular network around the implant, increasing solute transport to the encapsulated cells. Here, we present a replenishable prevascularized implantation methodology (RPVIM) that allows for the vascular integration of replenishable encapsulation devices in the subcutaneous space. Empty encapsulation devices were vascularized for 14 days, after which insulin-producing cells were inserted without disrupting the surrounding vasculature. The RPVIM devices were compared with nonprevascularized devices (Standard Implantation Methodology [SIM]) and previously established prevascularized devices (Standard Prevascularization Implantation Methodology [SPVIM]). Results show that over 75% of RPVIM devices containing stem cell-derived insulin-producing beta cell clusters Gauree Chendke and Bhushan Kharbikar contributed equally to this work.

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Xenotransplantation of tannic acid‐encapsulated neonatal porcine islets decreases proinflammatory innate immune responses

Cited by 11 publications

References 71 publications

Islet transplantation into brown adipose tissue can delay immune rejection

Islet transplantation into brown adipose tissue can delay immune rejection

Islet Encapsulation: New Developments for the Treatment of Type 1 Diabetes

Replenishable prevascularized cell encapsulation devices increase graft survival and function in the subcutaneous space

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