Immunoisolation of Pancreatic Islet Grafts with No Recipient’s Immunosuppression: Actual and Future Perspectives

Basta, Giuseppe; Calafiore, Riccardo

doi:10.1007/s11892-011-0219-6

Cited by 40 publications

(30 citation statements)

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“…Endotoxin content is a crucial factor in provoking purity-related inflammatory responses [18]. A concentration of <0.006 ng/mg is considered to be far below the level that could induce an inflammatory response [4,18] and below the endotoxin content of commercially available alginates. Also, we constructed capsules with an identical mechanical stability.…”

Section: Resultsmentioning

confidence: 99%

The association between in vivo physicochemical changes and inflammatory responses against alginate based microcapsules

et al. 2012

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Citation for published version (APA): de Vos, P., Spasojevic, M., de Haan, B., & Faas, M. M. (2012). The association between in vivo physicochemical changes and inflammatory responses against alginate based microcapsules. Biomaterials, 33(22), 5552-5559. a b s t r a c t Application of alginate-polylysine (PLL) capsules for immunoisolation of living cells are suffering from a varying degree of success and large lab-to-lab variations. In this study we show that these differences in success rates can be attributed to alginate dependent essential physicochemical changes of the properties of capsules in vivo that will render the capsules more susceptible to inflammatory responses. Capsule properties were studied before and after implantation by XPS, by immunocytochemistry, and by measuring zeta potentials. We studied a capsule type which provokes for unknown reasons a strong inflammatory response, i.e. high-guluronic (G) alginate capsules and a capsule type with near identical physicochemical properties but which evokes a minimal inflammatory response, i.e. intermediate-G alginate capsules. The cause of the difference in response was a decrease in nitrogen content on high-G capsules due to detachment of PLL in vivo and an increase of the zeta-potential. Our data illustrate an important overlooked phenomena; the physicochemical properties are not necessarily the properties after exposure to the in vivo microenvironment and might induce undesired inflammatory responses and failure of encapsulated cellular grafts.

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Section: Resultsmentioning

confidence: 99%

The association between in vivo physicochemical changes and inflammatory responses against alginate based microcapsules

et al. 2012

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“…Due to the suboptimal efficacy and safety associated with the procedure, islet transplantation is currently limited to cases of extreme necessity. Immunoisolation via cell encapsulation may allow transplantation without SI and increase the safety and clinical impact of the procedure (2)(3)(4)(5). Although encapsulation has been studied for the past 50 y (6), its clinical success, thus far, has been limited (2,4,(7)(8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

“…space, which is poorly vascularized and therefore less favorable to cell engraftment (16)(17)(18). Finally, materials used for conventional microencapsulation are based on alginate (ALG) hydrogels whose stability in vivo, including permselectivity to cytokines, antibodies, and cells, has been long argued (2,4,19).…”

mentioning

confidence: 99%

Device design and materials optimization of conformal coating for islets of Langerhans

Tomei

Manzoli

Fraker

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

172

145

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Encapsulation of islets of Langerhans may represent a way to transplant islets in the absence of immunosuppression. Traditional methods for encapsulation lead to diffusional limitations imposed by the size of the capsules (600-1,000 μm in diameter), which results in core hypoxia and delayed insulin secretion in response to glucose. Moreover, the large volume of encapsulated cells does not allow implantation in sites that might be more favorable to islet cell engraftment. To address these issues, we have developed an encapsulation method that allows conformal coating of islets through microfluidics and minimizes capsule size and graft volume. In this method, capsule thickness, rather than capsule diameter, is constant and tightly defined by the microdevice geometry and the rheological properties of the immiscible fluids used for encapsulation within the microfluidic system. We have optimized the method both computationally and experimentally, and found that conformal coating allows for complete encapsulation of islets with a thin (a few tens of micrometers) continuous layer of hydrogel. Both in vitro and in vivo in syngeneic murine models of islet transplantation, the function of conformally coated islets was not compromised by encapsulation and was comparable to that of unencapsulated islets. We have further demonstrated that the structural support conferred by the coating materials protected islets from the loss of function experienced by uncoated islets during ex vivo culture.cell encapsulation | polyethylene glycol | alginate | cell transplantation

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“…Encapsulation aims to create an artificial immune-privileged site, protecting the grafts from the host immune system. A successful device should contain membranes with selective permeability, to exclude large host immune cells and immunoglobulins, while permitting small molecules such as oxygen, carbon dioxide and essential nutrients to reach the cells, and insulin to be secreted in response to high blood glucose levels (5,24,25). Graft site is also an important consideration when designing an encapsulation device, as engrafted islets/cells must be able to respond rapidly to elevated circulating glucose levels.…”

Section: Whole Pancreas and Islet Transplantationmentioning

confidence: 99%

Recent Advances in Cell Replacement Therapies for the Treatment of Type 1 Diabetes

Cogger

Nostro

2015

Endocrinology

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Exogenous insulin administration is currently the only treatment available to all type 1 diabetes patients, but it is not a cure. By helping to regulate circulating blood glucose levels, it has significantly improved life expectancy, but there are still long-term complications associated with the disease that may be preventable with a treatment strategy that can provide better glycemic control. Isolated islet (or whole pancreas) transplantation, xenotransplantation, and the transplant of human pluripotent stem cell-derived β-cells provide the potential to restore endogenous insulin production and reestablish normoglycemia. Here, we discuss the latest advances in these fields, including the use of encapsulation technology, as well as some of the hurdles that still need to be overcome for these alternative therapies to become mainstream and/or progress to clinical development.

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Immunoisolation of Pancreatic Islet Grafts with No Recipient’s Immunosuppression: Actual and Future Perspectives

Cited by 40 publications

References 47 publications

The association between in vivo physicochemical changes and inflammatory responses against alginate based microcapsules

The association between in vivo physicochemical changes and inflammatory responses against alginate based microcapsules

Device design and materials optimization of conformal coating for islets of Langerhans

Recent Advances in Cell Replacement Therapies for the Treatment of Type 1 Diabetes

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