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Engineering and Characterization of a Biomimetic Microchip for Differentiating Mouse Adipocytes in a 3D Microenvironment

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Abstract

Although two-dimensional (2D) cell cultures are the standard in cell research, one pivotal disadvantage is the lack of cell–cell and cell-extracellular matrix (ECM) signaling in the culture milieu. However, such signals occur in three-dimensional (3D) in vivo environments and are essential for cell differentiation, proliferation, and a range of cellular functions. In this study, we developed a microfluidic device to proliferate and differentiate functional adipose tissue and adipocytes by utilizing 3D cell culture technology. This device was used to generate a tissue-specific 3D microenvironment to differentiate 3T3-L1 preadipocytes into either visceral white adipocytes using visceral adipose tissue (VAT) or subcutaneous white adipose tissue (SAT). The microchip has been tested and validated by functional assessments including cell morphology, inflammatory response to a lipopolysaccharide (LPS) challenge, GLUT4 tracking, and gene expression analyses. The biomimetic microfluidic chip is expected to mimic functional adipose tissues that can replace 2D cell cultures and allow for more accurate analysis of adipose tissue physiology.

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Acknowledgements

This work was supported by TTU New Faculty Start-up Funds for WL. and TTU Obesity Research Cluster Seed Funds for WL. and NMM. JYW, NMM and WL designed the experiments, YC, LR, CRG, and ZD conducted the experiments, all authors contributed to data analysis and the writing this manuscript.

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Correspondence to Jiangyu Wu, Naima Moustaid-Moussa or Wei Li.

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Chen, Yt., Ramalingam, L., Garcia, C.R. et al. Engineering and Characterization of a Biomimetic Microchip for Differentiating Mouse Adipocytes in a 3D Microenvironment. Pharm Res 39, 329–340 (2022). https://doi.org/10.1007/s11095-022-03195-0

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