Compact fluidic system for functional assessment of pancreatic islets

Hori, Takeshi; Yamane, Keisaku; Anazawa, Takayuki; Kurosawa, Osamu; Iwata, Hiroo

doi:10.1007/s10544-019-0443-4

Cited by 11 publications

(14 citation statements)

References 26 publications

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“…β-cells are the predominant cell type within the pancreatic islets in mammals and the unique source of circulating insulin, being fundamental for the maintenance of glucose homeostasis [ 30 , 31 , 32 ]. Unlike the other IOC devices that are based on multiple tiny wells to trap the islets [ 24 , 25 , 26 , 27 , 33 , 34 , 35 , 36 ], we have precisely engineered a heterogeneous porous cryogel scaffold which offers a robust approach for spatially organizing the islets, and which can limit shear-induced cell damage. It was recently demonstrated that 3D polymeric-based scaffolds offer mechanical and chemical properties that make them valuable in tissue engineering applications [ 37 ].…”

Section: Resultsmentioning

confidence: 99%

“…In this work, we present an integrated on-chip insulin secretion study platform, combining novel islet-on-a-chip (IOC) technology interfaced with an on-chip LSPR biosensing platform ( Figure 1 ). Unlike other IOC devices that are based on multiple tiny wells to trap the islets [ 24 , 25 , 26 , 27 ], which can promote shear stress-induced cell damage, we have developed an IOC that houses primary mouse pancreatic islets embedded in a non-biodegradable cellulose-based scaffold that intends to biomimic the native pancreas host. The integration of both platforms allows, for the first time, a highly sensitive and label-free monitoring of in situ insulin secretion by pancreatic islets subjected to different glucose concentrations, under physiological conditions, offering a powerful tool for future biomedicine and pharmaceutical research related to diabetes.…”

Section: Introductionmentioning

confidence: 99%

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In Situ LSPR Sensing of Secreted Insulin in Organ-on-Chip

et al. 2021

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Organ-on-a-chip (OOC) devices offer new approaches for metabolic disease modeling and drug discovery by providing biologically relevant models of tissues and organs in vitro with a high degree of control over experimental variables for high-content screening applications. Yet, to fully exploit the potential of these platforms, there is a need to interface them with integrated non-labeled sensing modules, capable of monitoring, in situ, their biochemical response to external stimuli, such as stress or drugs. In order to meet this need, we aim here to develop an integrated technology based on coupling a localized surface plasmon resonance (LSPR) sensing module to an OOC device to monitor the insulin in situ secretion in pancreatic islets, a key physiological event that is usually perturbed in metabolic diseases such as type 2 diabetes (T2D). As a proof of concept, we developed a biomimetic islet-on-a-chip (IOC) device composed of mouse pancreatic islets hosted in a cellulose-based scaffold as a novel approach. The IOC was interfaced with a state-of-the-art on-chip LSPR sensing platform to monitor the in situ insulin secretion. The developed platform offers a powerful tool to enable the in situ response study of microtissues to external stimuli for applications such as a drug-screening platform for human models, bypassing animal testing.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In Situ LSPR Sensing of Secreted Insulin in Organ-on-Chip

et al. 2021

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“…The applications of microfluidics for synchronized islet perfusion and fluorescent imaging to simultaneously detect live-cell changes in calcium influx and mitochondrial potentials were the base of a substantial number of devices. However, most of these were usually followed by off-line standard enzyme-linked immunosorbent assay (ELISA) to quantify the amount of secreted insulin [70]. Indeed, the impossibility to detect insulin in real-time has been one of the main limitations of different suitable designs that have been proposed to evaluate islet functionality in response to dynamic glucose stimulation.…”

Section: Multi-islet Screening By Ioc Technologymentioning

confidence: 99%

Islet-on-a-chip for the study of pancreatic β-cell function

Rodríguez‐Comas

Ramón‐Azcón

2021

In vitro models

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Diabetes mellitus is a significant public health problem worldwide. It encompasses a group of chronic disorders characterized by hyperglycemia, resulting from pancreatic islet dysfunction or as a consequence of insulin-producing β-cell death. Organ-on-a-chip platforms have emerged as technological systems combining cell biology, engineering, and biomaterial technological advances with microfluidics to recapitulate a specific organ’s physiological or pathophysiological environment. These devices offer a novel model for the screening of pharmaceutical agents and to study a particular disease. In the field of diabetes, a variety of microfluidic devices have been introduced to recreate native islet microenvironments and to understand pancreatic β-cell kinetics in vitro. This kind of platforms has been shown fundamental for the study of the islet function and to assess the quality of these islets for subsequent in vivo transplantation. However, islet physiological systems are still limited compared to other organs and tissues, evidencing the difficulty to study this “organ” and the need for further technological advances. In this review, we summarize the current state of islet-on-a-chip platforms that have been developed so far. We recapitulate the most relevant studies involving pancreatic islets and microfluidics, focusing on the molecular and cellular-scale activities that underlie pancreatic β-cell function.

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“…These include an islet and cell aggregate trap system which gently immobilizes cells and enables fluid contact with and flow around the islet surface. Islets can be trapped using a mesh system, 60 with narrowing of fluid channels, 61,62 or with troughs into which islets and cell aggregates will settle 63 . Alternatively, pseudoislets can be formed on the chip itself which can then be perfused during long‐term culture 55,64 .…”

Section: Engineered Fluidic Platforms For Studying Islets and Insulinmentioning

confidence: 99%

Engineering-inspired approaches to study β-cell function and diabetes

Lewis

Wells

2021

Stem Cells

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Strategies to mitigate the pathologies from diabetes range from simply administering insulin to prescribing complex drug/biologic regimens combined with lifestyle changes. There is a substantial effort to better understand β-cell physiology during diabetes pathogenesis as a means to develop improved therapies. The convergence of multiple fields ranging from developmental biology to microfluidic engineering has led to the development of new experimental systems to better study complex aspects of diabetes and β-cell biology. Here we discuss the available insulin-secreting cell types used in research, ranging from primary human β-cells, to cell lines, to pluripotent stem cell-derived β-like cells. Each of these sources possess inherent strengths and weaknesses pertinent to specific applications, especially in the context of engineered platforms. We then outline how insulin-expressing cells have been used in engineered platforms and how recent advances allow for better mimicry of in vivo conditions. Chief among these conditions are β-cell interactions with other endocrine organs. This facet is beginning to be thoroughly addressed by the organ-on-a-chip community, but holds enormous potential in the development of novel diabetes therapeutics. Furthermore, high throughput strategies focused on studying β-cell biology, improving β-cell differentiation, or proliferation have led to enormous contributions in the field and will no doubt be instrumental in bringing new diabetes therapeutics to the clinic.

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Compact fluidic system for functional assessment of pancreatic islets

Cited by 11 publications

References 26 publications

In Situ LSPR Sensing of Secreted Insulin in Organ-on-Chip

In Situ LSPR Sensing of Secreted Insulin in Organ-on-Chip

Islet-on-a-chip for the study of pancreatic β-cell function

Engineering-inspired approaches to study β-cell function and diabetes

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