Oxidative stress in pancreatic alpha and beta cells as a selection criterion for biocompatible biomaterials

Sthijns, Mireille M.J.P.E.; Jetten, Marlon J.; Mohammed, Sami G.; Claessen, Sandra; Vries, Rick de; Stell, Adam; Bont, Denise de; Engelse, Marten A.; Mumcuoglu, Didem; Blitterswijk, Clemens A. van; Dankers, Patricia Y. W.; Koning, Eelco J.P. de; Apeldoorn, Aart van; LaPointe, Vanessa

doi:10.1016/j.biomaterials.2020.120449

Cited by 11 publications

(13 citation statements)

References 76 publications

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“…Biomaterials’ selection should considerer their contribution to optimum redox state, as suggested by Sthijns et al ( Sthijns et al, 2021 ), who evaluated different polymers for a pancreatic islet encapsulation device; cell sensitivity to oxidative stress is variable and essential for cell survival, proliferation, and function ( Sthijns et al, 2021 ), and contributes to avoid chronic inflammation and peri-implantar fibrosis. As reviewed by Sthijns et al ( Sthijns et al, 2018 ), in tissue engineering approaches, ensuring adequate perfusion of the construct is paramount for cell survival and to avoid increased ROS formation.…”

Section: Discussionmentioning

confidence: 99%

In Sickness and in Health: The Oxygen Reactive Species and the Bone

Reis

Ramos

2021

Front. Bioeng. Biotechnol.

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Oxidative stress plays a central role in physiological and pathological bone conditions. Its role in signalment and control of bone cell population differentiation, activity, and fate is increasingly recognized. The possibilities of its use and manipulation with therapeutic goals are virtually unending. However, how redox balance interplays with the response to mechanical stimuli is yet to be fully understood. The present work summarizes current knowledge on these aspects, in an integrative and broad introductory perspective.

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Section: Discussionmentioning

confidence: 99%

In Sickness and in Health: The Oxygen Reactive Species and the Bone

Reis

Ramos

2021

Front. Bioeng. Biotechnol.

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“…The encapsulation process further enhances this effect since it prevents revascularization, while biomaterials used for encapsulation can potentially induce significant amounts of oxidative stress in both beta and alpha cells. [8] The absence of revascularization and a limited mass transport lead to ultimately to irreversible chronic hypoxia induced oxidative stress. Although microencapsulation is able to block immune cells and large antibodies, smaller molecules such as chemokines, cytokines, and reactive oxygen species (ROS), can easily permeate through the microcapsule's hydrogel network.…”

Section: Introductionmentioning

confidence: 99%

Fucoidan Hydrogels Significantly Alleviate Oxidative Stress and Enhance the Endocrine Function of Encapsulated Beta Cells

Reys

Vaithilingam

Sthijns

et al. 2021

Adv Funct Materials

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Microencapsulating pancreatic islets in immunoprotective alginate hydrogels is a promising strategy for treatment of type 1 diabetes. However, this strategy is limited by inflammation and hypoxia mediated oxidative stress, due to encapsulation and the hydrogel itself, leading to impaired insulin secretion and limited short and long term cell survival. Herein, the antioxidant effect of fucoidan, an algae derived polysaccharide, on beta cells, and its positive effects on encapsulated beta cell viability and function is presented. Fucoidan from Fucus vesiculosus (FF) exhibits a high total antioxidant capacity, and free radical scavenging activity, and is able to significantly alleviate intracellular oxidative stress in rat insolinoma beta cells (INS1E). In addition, FF significantly increases insulin secretion in a dose-and time-dependent manner. When FF is incorporated in ultrapure alginate used for microencapsulation of primary rat islets, both viability and glucose responsiveness of rat islets in these socalled Fucogel microcapsules (Fucocaps) are found to be significantly higher compared to islets encapsulated in alginate alone. Similar results are obtained with INS1E pseudoislets and neonatal pig islets. Fucocaps can provide a redox-modulatory niche and an immune barrier for islets and beta cells in the same time leading to significantly improved survival and endocrine function by mitigating oxidative stress.

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“…As a future outlook, it would be interesting to validate this finding in the context of beta cell replacement strategies, where the cells are known to experience high levels of oxidative stress [31,32,[43][44][45]. Engineered islets could be transplanted in the ratio of 50:50 beta:alpha cells to protect them against the oxidative stress they experience during transplantation and from biomaterials used for encapsulation [46]. This approach becomes a reasonable strategy as the differentiation of pluripotent stem cells into pancreatic endocrine cells can create engineered islets resembling their in vivo counterparts [47].…”

Section: Discussionmentioning

confidence: 96%

The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress

Sthijns

Rademakers

Oosterveer

et al. 2021

Preprint

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The pancreatic islets of Langerhans have low endogenous antioxidant levels and are thus especially sensitive to oxidative stress, which is known to influence cell survival and behaviour. As bioengineered islets are gaining interest for therapeutic purposes, it is important to understand how their composition can be optimized to diminish oxidative stress. We investigated how the ratio of the two main islet cell types (alpha and beta cells) and their culture in three-dimensional aggregates could protect against oxidative stress. Monolayer and aggregate cultures were established by seeding the alphaTC1 (alpha) and INS1E (beta) cell lines in varying ratios, and hydrogen peroxide was applied to induce oxidative stress. Viability, oxidative stress, and the level of the antioxidant glutathione were measured. Both aggregation and an increasing prevalence of INS1E cells in the co-cultures conferred greater resistance to cell death induced by oxidative stress. Increasing the prevalence of INS1E cells also decreased the number of alphaTC1 cells experiencing oxidative stress in the monolayer culture. In 3D aggregates, culturing the alphaTC1 and INS1E cells in a ratio of 50:50 prevented oxidative stress in both cell types. Together, the results of this study lead to new insight into how modulating the composition and dimensionality of a co-culture can influence the oxidative stress levels experienced by the cells.

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Oxidative stress in pancreatic alpha and beta cells as a selection criterion for biocompatible biomaterials

Cited by 11 publications

References 76 publications

In Sickness and in Health: The Oxygen Reactive Species and the Bone

In Sickness and in Health: The Oxygen Reactive Species and the Bone

Fucoidan Hydrogels Significantly Alleviate Oxidative Stress and Enhance the Endocrine Function of Encapsulated Beta Cells

The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress

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