Long-term biocompatibility, chemistry, and function of microencapsulated pancreatic islets

Vos, Paul de; Hoogmoed, Chris G. van; Zanten, Jacoba van; Netter, Susanne; Strubbe, J.H.; Busscher, Henk J.

doi:10.1016/s0142-9612(02)00319-8

Cited by 128 publications

(92 citation statements)

References 33 publications

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“…For subsequent encapsulation studies and/or testing transplantation studies, it is critical to be able to remove the aggregates from the devices. After removal from the microwells, the b-cell aggregates can be used for other biological experiments or encapsulated within other permissive biomaterials (e.g., PEGs 32 or alginates 39,40 ) for implantation. The use of PEG microwell arrays for b-cell aggregation yielded relatively uniform cell aggregates-demonstrated by narrow distributions of both aggregate diameter and cells per aggregate-which scaled in size with microwell dimension.…”

Section: Discussionmentioning

confidence: 99%

A Microwell Cell Culture Platform for the Aggregation of Pancreatic β-Cells

Bernard

Lin

Anseth

2012

Tissue Engineering Part C: Methods

119

138

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Cell-cell contact between pancreatic b-cells is important for maintaining survival and normal insulin secretion. Various techniques have been developed to promote cell-cell contact between b-cells, but a simple yet robust method that affords precise control over three-dimensional (3D) b-cell cluster size has not been demonstrated. To address this need, we developed a poly(ethylene glycol) (PEG) hydrogel microwell platform using photolithography. This microwell cell-culture platform promotes the formation of 3D b-cell aggregates of defined sizes from 25 to 210 mm in diameter. Using this platform, mouse insulinoma 6 (MIN6) b-cells formed aggregates with cell-cell adherin junctions. These naturally formed cell aggregates with controllable sizes can be removed from the microwells for macroencapsulation, implantation, or other biological assays. When removed and subsequently encapsulated in PEG hydrogels, the aggregated cell clusters demonstrated improved cellular viability ( > 90%) over 7 days in culture, while the b-cells encapsulated as single cells maintained only 20% viability. Aggregated MIN6 cells also exhibited more than fourfold higher insulin secretion in response to a glucose challenge compared with encapsulated single b-cells. Further, the cell aggregates stained positively for E-cadherin, indicative of the formation of cell junctions. Using this hydrogel microwell cell-culture method, viable and functional b-cell aggregates of specific sizes were created, providing a platform from which other biologically relevant questions may be answered.

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Section: Discussionmentioning

confidence: 99%

A Microwell Cell Culture Platform for the Aggregation of Pancreatic β-Cells

Bernard

Lin

Anseth

2012

Tissue Engineering Part C: Methods

119

138

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“…Therefore, Omer et al (2005) prepared alginate microcapsules by cross-linking with barium chloride without adding the PLL coating. Longer (ϳ28 weeks) normoglycemic time was observed with alginate-BaCl 2 microcapsules (Omer et al, 2005) compared with ϳ10 to 15 weeks with alginate-PLL microcapsules (De Vos et al, 2003). BaCl 2 crosslinked microcapsules perform better than CaCl 2 crosslinked microcapsules, because barium cross-linkage results in stronger alginate gels than those made with calcium .…”

Section: A Immunoisolation Of Transplanted Isletsmentioning

confidence: 97%

Biological and Biomaterial Approaches for Improved Islet Transplantation

2006

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“…4,9,24 Histological and immunohistochemical methods are also frequently used but are invasive and destructive, do not allow for three dimensional (3D) assessment of the sample, often alter biomaterial structure, and require processing and staining techniques. 4,[24][25][26][27][28][29] There is a need for noninvasive imaging that allows for 3D assessment of the implanted grafts and local tissue response to monitor and predict long-term success of the transplant. The ideal imaging technique would not require exogenous contrast and be nondestructive.…”

mentioning

confidence: 99%

Imaging of Hydrogel Microsphere Structure and Foreign Body Response Based on Endogenous X-Ray Phase Contrast

Appel

Ibarra

Somo

et al. 2016

Tissue Engineering Part C: Methods

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Transplantation of functional islets encapsulated in stable biomaterials has the potential to cure Type I diabetes. However, the success of these materials requires the ability to quantitatively evaluate their stability. Imaging techniques that enable monitoring of biomaterial performance are critical to further development in the field. Xray phase-contrast (XPC) imaging is an emerging class of X-ray techniques that have shown significant promise for imaging biomaterial and soft tissue structures. In this study, XPC imaging techniques are shown to enable three dimensional (3D) imaging and evaluation of islet volume, alginate hydrogel structure, and local soft tissue features ex vivo. Rat islets were encapsulated in sterile ultrapurified alginate systems produced using a highthroughput microfluidic system. The encapsulated islets were implanted in omentum pouches created in a rodent model of type 1 diabetes. Microbeads were imaged with XPC imaging before implantation and as whole tissue samples after explantation from the animals. XPC microcomputed tomography (mCT) was performed with systems using tube-based and synchrotron X-ray sources. Islets could be identified within alginate beads and the islet volume was quantified in the synchrotron-based mCT volumes. Omental adipose tissue could be distinguished from inflammatory regions resulting from implanted beads in harvested samples with both XPC imaging techniques. Individual beads and the local encapsulation response were observed and quantified using quantitative measurements, which showed good agreement with histology. The 3D structure of the microbeads could be characterized with XPC imaging and failed beads could also be identified. These results point to the substantial potential of XPC imaging as a tool for imaging biomaterials in small animal models and deliver a critical step toward in vivo imaging.

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Long-term biocompatibility, chemistry, and function of microencapsulated pancreatic islets

Cited by 128 publications

References 33 publications

A Microwell Cell Culture Platform for the Aggregation of Pancreatic β-Cells

A Microwell Cell Culture Platform for the Aggregation of Pancreatic β-Cells

Biological and Biomaterial Approaches for Improved Islet Transplantation

Imaging of Hydrogel Microsphere Structure and Foreign Body Response Based on Endogenous X-Ray Phase Contrast

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