Structure, Function, and Immune Properties of Reassociated Islet Cells

Shizuru, Judith A.; Trager, D.; Merrell, Ronald C.

doi:10.2337/diab.34.9.898

Cited by 14 publications

(3 citation statements)

References 9 publications

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“…Additionally, quickly after isolation, islets decline in viability and functionality with regard to their glucose responsiveness 46,47. It has long been known that dissociated isolated islets can spontaneously reaggregate into islet‐like clusters, with native‐like architecture and secretory function 37,48–50. The reaggregation process also provides control over the islet size, which enables the generation of smaller islets.…”

Section: Resultsmentioning

confidence: 99%

In Vitro Platform for Studying Human Insulin Release Dynamics of Single Pancreatic Islet Microtissues at High Resolution

et al. 2020

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Insulin is released from pancreatic islets in a biphasic and pulsatile manner in response to elevated glucose levels. This highly dynamic insulin release can be studied in vitro with islet perifusion assays. Herein, a novel platform to perform glucose‐stimulated insulin secretion (GSIS) assays with single islets is presented for studying the dynamics of insulin release at high temporal resolution. A standardized human islet model is developed and a microfluidic hanging‐drop‐based perifusion system is engineered, which facilitates rapid glucose switching, minimal sample dilution, low analyte dispersion, and short sampling intervals. Human islet microtissues feature robust and long‐term glucose responsiveness and demonstrate reproducible dynamic GSIS with a prominent first phase and a sustained, pulsatile second phase. Perifusion of single islet microtissues produces a higher peak secretion rate, higher secretion during the first and second phases of insulin release, as well as more defined pulsations during the second phase in comparison to perifusion of pooled islets. The developed platform enables to study compound effects on both phases of insulin secretion as shown with two classes of insulin secretagogs. It provides a new tool for studying physiologically relevant dynamic insulin secretion at comparably low sample‐to‐sample variation and high temporal resolution.

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Section: Resultsmentioning

confidence: 99%

In Vitro Platform for Studying Human Insulin Release Dynamics of Single Pancreatic Islet Microtissues at High Resolution

et al. 2020

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“…It has long been known that isolated islets can be dissociated into single cells, which spontaneously reaggregate into islet‐like clusters, so‐called ‘pseudo‐islets’. Such pseudo‐islets have been described to be comparable to intact islets in terms of cellular composition, architecture and secretory function, while their immunogenicity in the transplant setting seems to be attenuated, but greater islet loss was observed during production (Halban et al ., ; King et al ., ; Matta et al ., ; Shizuru et al ., ; Wolf‐Jochim et al ., ). Formation of cellular aggregates can also be achieved by the ‘hanging‐drop’ culture method, which was described previously for a variety of systems, e.g.…”

Section: Introductionmentioning

confidence: 99%

Improved physiological properties of gravity-enforced reassembled rat and human pancreatic pseudo-islets

Zuellig

Cavallari

Gerber

et al. 2014

J Tissue Eng Regen Med

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Previously we demonstrated the superiority of small islets vs large islets in terms of function and survival after transplantation, and we generated reaggregated rat islets (pseudo-islets) of standardized small dimensions by the hanging-drop culture method (HDCM). The aim of this study was to generate human pseudo-islets by HDCM and to evaluate and compare the physiological properties of rat and human pseudo-islets. Isolated rat and human islets were dissociated into single cells and incubated for 6-14 days by HDCM. Newly formed pseudo-islets were analysed for dimensions, morphology, glucose-stimulated insulin secretion (GSIS) and total insulin content. The morphology of reaggregated human islets was similar to that of native islets, while rat pseudo-islets had a reduced content of α and δ cells. GSIS of small rat and human pseudo-islets (250 cells) was increased up to 4.0-fold (p < 0.01) and 2.5-fold (p < 0.001), respectively, when compared to their native counterparts. Human pseudo-islets showed a more pronounced first-phase insulin secretion as compared to intact islets. GSIS was inversely correlated to islet size, and small islets (250 cells) contained up to six-fold more insulin/cell than large islets (1500 cells). Tissue loss with this new technology could be reduced to 49.2 ± 1.5% in rat islets, as compared to the starting amount. With HDCM, pseudo-islets of standardized size with similar cellular composition and improved biological function can be generated, which compensates for tissue loss during production. Transplantation of small pseudo-islets may represent an attractive strategy to improve graft survival and function, due to better oxygen and nutrient supply during the phase of revascularization. Copyright © 2014 John Wiley & Sons, Ltd.

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“…32,33 Reassociated pseudoislets have been shown to be fully functional and to exhibit decreased immunogenicity toward lymphocytes. 34 Additionally, researchers have identified uniformly sized pseudoislets that can remain viable and functional under harsh hypoxic conditions due to their small dimensions. 27 We have previously reported an effective approach for anti-apoptotic and angiogenic effects on pancreatic islets using a heterospheroid system, where islet single cells and mesenchymal stem cells were coaggregated by using the hanging drop technique to form islet-like spheroids, and significant attenuation of cell death and enriched vascularization were observed.…”

Section: Introductionmentioning

confidence: 99%

Hybrid Congregation of Islet Single Cells and Curcumin-Loaded Polymeric Microspheres as an Interventional Strategy to Overcome Apoptosis Associated with Pancreatic Islets Transplantation

Pathak

Regmi

Gupta

et al. 2016

ACS Appl. Mater. Interfaces

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Hypoxic or near-anoxic conditions that occur in the core of transplanted islets induce necrosis and apoptosis during the early stages after transplantation, primarily due to loss of vascularization during the isolation process. Moreover, secretion of various cytokines from pancreatic islets is detrimental to the viability of islet cells in vitro. In this study, we aimed to protect pancreatic islet cells against apoptosis by establishing a method for in situ delivery of curcumin to the pancreatic islets. Self-assembled heterospheroids composed of pancreatic islet cells and curcumin-loaded polymeric microspheres were prepared by the three-dimensional cell culture technique. Release of curcumin in the microenvironment of pancreatic islets promoted survival of the islets. In hypoxic culture conditions, which mimic the in vivo conditions after transplantation, viability of the islets was significantly improved, as indicated by a decreased expression of pro-apoptotic protein and an increased expression of anti-apoptotic protein. Additionally, oxidative stress-induced cell death was suppressed. Thus, unlike co-transplantation of pancreatic islets and free microspheres, which provided a wide distribution of microspheres throughout the transplanted area, the heterospheroid transplantation resulted in colocalization of pancreatic islet cells and microspheres, thereby exerting beneficial effects on the cells.

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Structure, Function, and Immune Properties of Reassociated Islet Cells

Cited by 14 publications

References 9 publications

In Vitro Platform for Studying Human Insulin Release Dynamics of Single Pancreatic Islet Microtissues at High Resolution

In Vitro Platform for Studying Human Insulin Release Dynamics of Single Pancreatic Islet Microtissues at High Resolution

Improved physiological properties of gravity-enforced reassembled rat and human pancreatic pseudo-islets

Hybrid Congregation of Islet Single Cells and Curcumin-Loaded Polymeric Microspheres as an Interventional Strategy to Overcome Apoptosis Associated with Pancreatic Islets Transplantation

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