Multiplexed microfluidic platform for stem-cell derived pancreatic islet β cells

Goswami, Ishan; Klerk, Eleonora de; Carnese, Phichitpol; Hebrok, Matthias; Healy, Kevin E.

doi:10.1039/d2lc00468b

Cited by 12 publications

(6 citation statements)

References 48 publications

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“…Diabetes research has faced persistent challenges due to the absence of genuine disease models that should ideally be unlimited and capable of replicating the abnormalities associated with the development, structure, and function of human islets in pathological conditions ( Zhang et al, 2022 ). An appealing alternative for human islets for diabetes research, yet a significant challenge in the field involves creating mature and functional islet cells derived from stem cells, which has been increasingly explored recently ( Rogal et al, 2019 ; Balboa et al, 2021 ; Goswami et al, 2022 ; Yin et al, 2022 ; Vandana et al, 2023 ). Despite enormous progress that has been made in generating beta cells from stem cells, the beta cell differentiation efficiency varies across different cell lines and labs, and functional maturation is not complete in vitro ( Balboa et al, 2022 ; Fantuzzi et al, 2022 ; Iworima et al, 2024 ).…”

Section: Discussionmentioning

confidence: 99%

Cell identity dynamics and insight into insulin secretagogues when employing stem cell-derived islets for disease modeling

Wang,

Abadpour,

Aizenshtadt

et al. 2024

Front. Bioeng. Biotechnol.

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Stem cell-derived islets (SC-islets) are not only an unlimited source for cell-based therapy of type 1 diabetes but have also emerged as an attractive material for modeling diabetes and conducting screening for treatment options. Prior to SC-islets becoming the established standard for disease modeling and drug development, it is essential to understand their response to various nutrient sources in vitro. This study demonstrates an enhanced efficiency of pancreatic endocrine cell differentiation through the incorporation of WNT signaling inhibition following the definitive endoderm stage. We have identified a tri-hormonal cell population within SC-islets, which undergoes reduction concurrent with the emergence of elevated numbers of glucagon-positive cells during extended in vitro culture. Over a 6-week period of in vitro culture, the SC-islets consistently demonstrated robust insulin secretion in response to glucose stimulation. Moreover, they manifested diverse reactivity patterns when exposed to distinct nutrient sources and exhibited deviant glycolytic metabolic characteristics in comparison to human primary islets. Although the SC-islets demonstrated an aberrant glucose metabolism trafficking, the evaluation of a potential antidiabetic drug, pyruvate kinase agonist known as TEPP46, significantly improved in vitro insulin secretion of SC-islets. Overall, this study provided cell identity dynamics investigation of SC-islets during prolonged culturing in vitro, and insights into insulin secretagogues. Associated advantages and limitations were discussed when employing SC-islets for disease modeling.

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Section: Discussionmentioning

confidence: 99%

Cell identity dynamics and insight into insulin secretagogues when employing stem cell-derived islets for disease modeling

Wang,

Abadpour,

Aizenshtadt

et al. 2024

Front. Bioeng. Biotechnol.

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“…Goswami et al developed a device that reaggregated and cultured stem cell-derived β-cells in conjunction with a microfluidic gradient generator. 48 This device consisted of three layers; a media channel, PET membrane, and a microwell cell chamber (Fig. 2E).…”

Section: Benefits Of Microfluidic Platformmentioning

confidence: 99%

Twenty years of islet-on-a-chip: microfluidic tools for dissecting islet metabolism and function

Regeenes,

Rocheleau

2024

Lab Chip

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“…[25,26] The uneven coating and unwanted filling of microchannels by the interfacing materials are further obstacles commonly associated with such methods. [27] With the recent emergence of microphysiological systems (MPS) that are based on compartmentalized perfused devices of often hybrid nature, [28,29] the need for appropriate back-end processing techniques has been brought to the spotlight. In such settings, device surfaces and bonding materials should not manifest a high level of monomer leaching, nor any toxicity toward different organotypic cell models.…”

Section: Introductionmentioning

confidence: 99%

Robust and Seamless Integration of Thiol‐Ene‐Epoxy Thermosets with Thermoplastics and Glass as Hybrid Microfluidic Devices Suitable for Drug Studies

Harris,

Kaveh,

Kemas

et al. 2024

Adv Materials Inter

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Facile, durable and biocompatible integration of hybrid Lab‐on‐a‐Chip devices has remained an important challenge in microengineering. Here, the robust and seamless integration of off‐stoichiometry thiol‐ene‐epoxy (OSTE+) thermosets with a diverse range of thermoplastic and glass materials is demonstrated. While direct bonding offers sturdy proprieties for the majority of the material hybrids (up to 1.5 MPa), further surface priming enhances the bonding strength for those of lower surface energy (up to seven‐fold). Using microfluidic devices with a unique configuration of chambers and microchannels down to 100 µm, the impact of various bonding methods on their fluidic functionality is further shown. To investigate the utility of hybrid devices for pharmacological and toxicological studies, both pristine and primed devices are benchmarked against polydimethylsiloxane (PDMS) with regard to cell biocompatibility and drug absorption. While being on par with PDMS in terms of cell viability, pristine OSTE+ devices show an 11‐fold lower absorption of hydrophobic drug molecules. Although surface priming enhances the bonding strength, it compromises other criteria in device performance and biological applications. Combined, results demonstrate a novel integration approach for facile manufacturing of hybrid microfluidic devices using a material toolbox suitable for cell and pharmaceutical studies.

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Multiplexed microfluidic platform for stem-cell derived pancreatic islet β cells

Abstract: Multiplexed microphysiological system as a high-content, higher throughput device for stem cell-derived β cell culture and drug screening.

Cited by 12 publications

References 48 publications

Cell identity dynamics and insight into insulin secretagogues when employing stem cell-derived islets for disease modeling

Cell identity dynamics and insight into insulin secretagogues when employing stem cell-derived islets for disease modeling

Twenty years of islet-on-a-chip: microfluidic tools for dissecting islet metabolism and function

Robust and Seamless Integration of Thiol‐Ene‐Epoxy Thermosets with Thermoplastics and Glass as Hybrid Microfluidic Devices Suitable for Drug Studies

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