Development of In Vitro 3D TissueFlex® Islet Model for Diabetic Drug Efficacy Testing

Li, Zhaohui; Sun, He; Zhang, Haijiao; Meng, Fanyu; Cui, Zhanfeng

doi:10.1371/journal.pone.0072612

Cited by 18 publications

(18 citation statements)

References 45 publications

(64 reference statements)

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“…Thus, the 3D islet models have become attractive with great potential for high-throughput drug screening. Most importantly, the patterns of insulin release in response to the drug treatment using 3D islet models are in agreement with the data obtained in vivo (Li et al, 2013). Besides, numerous tests have proven that the 3D islet models in vitro have longterm cell viability (Gazda et al, 2007;Lee et al, 2012), while the isolated islets rapidly lose their mass and viability (Clayton & London, 1996;Olson et al, 2000).…”

Section: Applications Of In Vitro 3d Islet Modelssupporting

confidence: 81%

Engineering of microscale three-dimensional pancreatic islet modelsin vitroand their biomedical applications

Gao

Wang

Han

et al. 2015

Critical Reviews in Biotechnology

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Diabetes now is the most common chronic disease in the world inducing heavy burden for the people's health. Based on this, diabetes research such as islet function has become a hot topic in medical institutes of the world. Today, in medical institutes, the conventional experiment platform in vitro is monolayer cell culture. However, with the development of micro- and nano-technologies, several microengineering methods have been developed to fabricate three-dimensional (3D) islet models in vitro which can better mimic the islet of pancreases in vivo. These in vitro islet models have shown better cell function than monolayer cells, indicating their great potential as better experimental platforms to elucidate islet behaviors under both physiological and pathological conditions, such as the molecular mechanisms of diabetes and clinical islet transplantation. In this review, we present the state-of-the-art advances in the microengineering methods for fabricating microscale islet models in vitro. We hope this will help researchers to better understand the progress in the engineering 3D islet models and their biomedical applications such as drug screening and islet transplantation.

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Section: Applications Of In Vitro 3d Islet Modelssupporting

confidence: 81%

Engineering of microscale three-dimensional pancreatic islet modelsin vitroand their biomedical applications

Gao

Wang

Han

et al. 2015

Critical Reviews in Biotechnology

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“…These systems are often very small, that is, down to microreactor scales of a few milliliters. Microreactors in a microtiter well format can be suitable for drug screening [ 102 ], but larger bioreactor concepts are needed for the high-cell-mass expansion and cultivation of beta cells as discussed below.…”

Section: Bioreactor Technologies For 3d Beta Cell Approachesmentioning

confidence: 99%

Three-Dimensional Bioreactor Technologies for the Cocultivation of Human Mesenchymal Stem/Stromal Cells and Beta Cells

Petry

Weidner

Czermak

et al. 2018

Stem Cells International

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Diabetes is a prominent health problem caused by the failure of pancreatic beta cells. One therapeutic approach is the transplantation of functional beta cells, but it is difficult to generate sufficient beta cells in vitro and to ensure these cells remain viable at the transplantation site. Beta cells suffer from hypoxia, undergo apoptosis, or are attacked by the host immune system. Human mesenchymal stem/stromal cells (hMSCs) can improve the functionality and survival of beta cells in vivo and in vitro due to direct cell contact or the secretion of trophic factors. Current cocultivation concepts with beta cells are simple and cannot exploit the favorable properties of hMSCs. Beta cells need a three-dimensional (3D) environment to function correctly, and the cocultivation setup is therefore more complex. This review discusses 3D cultivation forms (aggregates, capsules, and carriers) for hMSCs and beta cells and strategies for large-scale cultivation. We have determined process parameters that must be balanced and considered for the cocultivation of hMSCs and beta cells, and we present several bioreactor setups that are suitable for such an innovative cocultivation approach. Bioprocess engineering of the cocultivation processes is necessary to achieve successful beta cell therapy.

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“…From this point of view, tissue-engineered scaffolds represent a valid alternative to effectively support pancreatic cell culture and secretion of hormones and polypeptides, while bioreactors are useful tools to provide the required perfusion conditions to prevent in vitro cell necrosis (Bentsi-Barnes et al, 2011; Li et al, 2013b). …”

Section: Pancreas In Vitro Modelsmentioning

confidence: 99%

Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models

Caddeo

Boffito

Sartori

2017

Front. Bioeng. Biotechnol.

212

172

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In the tissue engineering (TE) paradigm, engineering and life sciences tools are combined to develop bioartificial substitutes for organs and tissues, which can in turn be applied in regenerative medicine, pharmaceutical, diagnostic, and basic research to elucidate fundamental aspects of cell functions in vivo or to identify mechanisms involved in aging processes and disease onset and progression. The complex three-dimensional (3D) microenvironment in which cells are organized in vivo allows the interaction between different cell types and between cells and the extracellular matrix, the composition of which varies as a function of the tissue, the degree of maturation, and health conditions. In this context, 3D in vitro models can more realistically reproduce a tissue or organ than two-dimensional (2D) models. Moreover, they can overcome the limitations of animal models and reduce the need for in vivo tests, according to the “3Rs” guiding principles for a more ethical research. The design of 3D engineered tissue models is currently in its development stage, showing high potential in overcoming the limitations of already available models. However, many issues are still opened, concerning the identification of the optimal scaffold-forming materials, cell source and biofabrication technology, and the best cell culture conditions (biochemical and physical cues) to finely replicate the native tissue and the surrounding environment. In the near future, 3D tissue-engineered models are expected to become useful tools in the preliminary testing and screening of drugs and therapies and in the investigation of the molecular mechanisms underpinning disease onset and progression. In this review, the application of TE principles to the design of in vitro 3D models will be surveyed, with a focus on the strengths and weaknesses of this emerging approach. In addition, a brief overview on the development of in vitro models of healthy and pathological bone, heart, pancreas, and liver will be presented.

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Development of In Vitro 3D TissueFlex® Islet Model for Diabetic Drug Efficacy Testing

Cited by 18 publications

References 45 publications

Engineering of microscale three-dimensional pancreatic islet modelsin vitroand their biomedical applications

Engineering of microscale three-dimensional pancreatic islet modelsin vitroand their biomedical applications

Three-Dimensional Bioreactor Technologies for the Cocultivation of Human Mesenchymal Stem/Stromal Cells and Beta Cells

Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models

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