Fabrication of three-dimensional islet models by the geometry-controlled hanging-drop method

Gao, Bin; Jing, Ce; Ng, Kelvin; Pingguan‐Murphy, Belinda; Yang, Qingzhen

doi:10.1007/s10409-019-00856-z

Cited by 22 publications

(16 citation statements)

References 37 publications

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“…The lack of a 3D structure has been proven to be one of the main problems associated with decreased functionality [30]. Despite this limitation, many in vitro approaches focused on generating 3D functional pancreatic tissue using hanging-drop methods [31] or cell encapsulation into hydrogels [13,32]. The origin of the pancreatic cells is from animals, cadaveric donors, or immortalized cell lines.…”

Section: Cryogel Scaffold Characterizationmentioning

confidence: 99%

Cellulose-based scaffolds enhance pseudoislets formation and functionality

2021

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In vitro research for the study of type 2 diabetes (T2D) is frequently limited by the availability of a functional model for islets of Langerhans. To overcome the limitations of obtaining pancreatic islets from different sources, such as animal models or human donors, immortalized cell lines as the insulin-producing INS1E β-cells have appeared as a valid alternative to model insulin-related diseases. However, immortalized cell lines are mainly used in flat surfaces or monolayer distributions, not resembling the spheroid-like architecture of the pancreatic islets. To generate islet-like structures, the use of scaffolds appeared as a valid tool to promote cell aggregations. Traditionally-used hydrogel encapsulation methods do not accomplish all the requisites for pancreatic tissue engineering, as its poor nutrient and oxygen diffusion induces cell death. Here, we use cryogelation technology to develop a more resemblance scaffold with the mechanical and physical properties needed to engineer pancreatic tissue. This study shows that carboxymethyl cellulose (CMC) cryogels prompted cells to generate β-cell clusters in comparison to gelatin-based scaffolds, that did not induce this cell organization. Moreover, the high porosity achieved with CMC cryogels allowed us to create specific range pseudoislets. Pseudoislets formed within CMC-scaffolds showed cell viability for up to 7 d and a better response to glucose over conventional monolayer cultures. Overall, our results demonstrate that CMC-scaffolds can be used to control the organization and function of insulin-producing β-cells, representing a suitable technique to generate β-cell clusters to study pancreatic islet function.

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Section: Cryogel Scaffold Characterizationmentioning

confidence: 99%

Cellulose-based scaffolds enhance pseudoislets formation and functionality

2021

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“…The principle of cellular spheroidal formation is to prevent cells from spreading on the substrates and facilitate their selfaggregation. To this end, several strategies based on steric hindrance, [6] forced-floating, [7] centrifugal force, [8] shear force, [9] surface tension, [10] and gravity have been developed. [11] The stirring bioreactors (such as NASA bioreactors) have been proposed to high-throughput fabricate the 3D cellular spheroids, [12] but presenting poor performances in the biocompatibility and size control.…”

mentioning

confidence: 99%

Close to Real: Large‐Volume 3D Cell Spheroids on a Superamphiphobic Surface

Dai

Wang

et al. 2021

Adv Materials Inter

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3D cell spheroids with native cell‐to‐cell junctions and cell‐extracellular matrix interactions can recapitulate the comprehensive physiological environments in vivo, providing new platforms for preclinical drug screening. However, the applications of 3D cell spheroids are limited by the unmatched size, deficient cell abundance, and short service time. In this work, a novel upward culture method on a porous silica superamphiphobic biointerface (SABI) is developed to fully overcome these technical hurdles. Cell suspensions maintain in a state of aquatic marble, accelerating cellular self‐aggregation. Contributing to the upward culture model, this strategy overcomes the shortages of size limitation and media refreshing in the classical methods. Herein, large‐volume 3D cell spheroids with the size of over 1500 µm can be efficiently established within 2 days and subsequently long‐term cultured for more than 20 days. For a close to real biomimetic microenvironment, breast tumor 3D spheroid is applied as a proof of concept, simultaneously employing MCF‐7 cell, cancer‐associated fibroblast (clone 8), and vascular endothelial cell (HUVEC). The large‐volume tumor spheroid with close‐to‐real microenvironment services as a unique paradigm for all‐in‐one biological relevant researches, including the capacity of in situ observation, long‐term incubation, drug screening, and recyclability.

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“…For example, Pagliuca et al used a stirring plate to constantly rotate hPSCs cultured in spinner flasks to generate ~100-200 µm-sized cell clusters. Morphologically and functionally, these clusters resembled native human islets; however, few non-beta endocrine cells were detected compared to those in human islets [79,111]. Guo-Parke also showed that islet models prepared by the self-assembly method exhibited a 1.7-to 12.5-fold increase in insulin secretion in response to acute stimulation (e.g., glucose, amino acids, incretin hormones, or drugs) compared with equivalent cell monolayers.…”

Section: Organoidsmentioning

confidence: 89%

In Vitro Disease Models of the Endocrine Pancreas

et al. 2021

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The ethical constraints and shortcomings of animal models, combined with the demand to study disease pathogenesis under controlled conditions, are giving rise to a new field at the interface of tissue engineering and pathophysiology, which focuses on the development of in vitro models of disease. In vitro models are defined as synthetic experimental systems that contain living human cells and mimic tissue- and organ-level physiology in vitro by taking advantage of recent advances in tissue engineering and microfabrication. This review provides an overview of in vitro models and focuses specifically on in vitro disease models of the endocrine pancreas and diabetes. First, we briefly review the anatomy, physiology, and pathophysiology of the human pancreas, with an emphasis on islets of Langerhans and beta cell dysfunction. We then discuss different types of in vitro models and fundamental elements that should be considered when developing an in vitro disease model. Finally, we review the current state and breakthroughs in the field of pancreatic in vitro models and conclude with some challenges that need to be addressed in the future development of in vitro models.

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Fabrication of three-dimensional islet models by the geometry-controlled hanging-drop method

Cited by 22 publications

References 37 publications

Cellulose-based scaffolds enhance pseudoislets formation and functionality

Cellulose-based scaffolds enhance pseudoislets formation and functionality

Close to Real: Large‐Volume 3D Cell Spheroids on a Superamphiphobic Surface

In Vitro Disease Models of the Endocrine Pancreas

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