Optimized scaffold-free human 3D adipose tissue organoid culture for obesity and disease modeling
Obesity and type 2 diabetes (T2D) are strongly linked to abnormal adipocyte metabolism and adipose tissue (AT) dysfunction. However, existing adipose tissue models have limitations, particularly in the stable culture of fat cells that maintain physiologically relevant phenotypes, hindering a deeper...
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Elsevier
2025-03-01
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| Series: | SLAS Discovery |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2472555225000115 |
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| author | Rafael Dariolli Raphael Nir Tova Mushlam Glauco R. Souza Stephen R. Farmer Miguel L Batista, Jr. |
| author_facet | Rafael Dariolli Raphael Nir Tova Mushlam Glauco R. Souza Stephen R. Farmer Miguel L Batista, Jr. |
| author_sort | Rafael Dariolli |
| collection | DOAJ |
| description | Obesity and type 2 diabetes (T2D) are strongly linked to abnormal adipocyte metabolism and adipose tissue (AT) dysfunction. However, existing adipose tissue models have limitations, particularly in the stable culture of fat cells that maintain physiologically relevant phenotypes, hindering a deeper understanding of adipocyte biology and the molecular mechanisms behind differentiation. Current model systems fail to fully replicate In vivo metabolism, posing challenges in adipose tissue research. Three-dimensional (3D) AT organoids, although promising, present significant handling challenges during long-term culture. As adipocytes maturate and accumulate fat, they develop organotypic characteristics, increasing the buoyancy effect, which causes the organoids to oscillate, complicating culture manipulation and rendering multiple handling steps difficult.Due to these challenges, most adipose spheroid and organoid models are scaffold-based, despite many cell types' ability to secrete extracellular matrix (ECM) components and self-assemble into aggregates. Scaffold-free 3D organoids have been less explored. To address the shortage of affordable and reliable AT models, we utilized magnetic bioprinting technology to develop a human-derived 3D model of adipose tissue. This system incorporates a magnetic holder that restrains organoids, preventing them from floating and minimizing the risk of loss during manipulation.This study outlines a protocol for generating In vitro AT-derived organoid using 3D magnetic bioprinting, with a focus on manufacturing, culturing, and assessing the morpho-functional characteristics of late-stage AT organoids. Magnetic bioprinting allows for the replication of tissue structure and function In vitro without the risk of organoid loss, making it an ideal method for high-throughput AT organoid culture. Additionally, the combination of 3D scaffold-free manufacturing with In vitro disease modeling offers a valuable tool for discovering treatments for metabolic diseases such as obesity and T2D. |
| format | Article |
| id | doaj-art-2a0ec6579fa3473591aaf15400f77033 |
| institution | Kabale University |
| issn | 2472-5552 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | SLAS Discovery |
| spelling | doaj-art-2a0ec6579fa3473591aaf15400f770332025-02-03T04:16:50ZengElsevierSLAS Discovery2472-55522025-03-0131100218Optimized scaffold-free human 3D adipose tissue organoid culture for obesity and disease modelingRafael Dariolli0Raphael Nir1Tova Mushlam2Glauco R. Souza3Stephen R. Farmer4Miguel L Batista, Jr.5Bonds Biosystems, 27 Strathmore Rd, Natick, MA, USA; Corresponding authors.SBH, 27 Strathmore Rd, Natick, MA, USADepartment of Biochemistry, Boston University School of Medicine, Boston, MA, USAGreiner Bio-One North America, Inc., 4238 Capital Drive, Monroe, NC 28110, USADepartment of Biochemistry, Boston University School of Medicine, Boston, MA, USABonds Biosystems, 27 Strathmore Rd, Natick, MA, USA; Corresponding authors.Obesity and type 2 diabetes (T2D) are strongly linked to abnormal adipocyte metabolism and adipose tissue (AT) dysfunction. However, existing adipose tissue models have limitations, particularly in the stable culture of fat cells that maintain physiologically relevant phenotypes, hindering a deeper understanding of adipocyte biology and the molecular mechanisms behind differentiation. Current model systems fail to fully replicate In vivo metabolism, posing challenges in adipose tissue research. Three-dimensional (3D) AT organoids, although promising, present significant handling challenges during long-term culture. As adipocytes maturate and accumulate fat, they develop organotypic characteristics, increasing the buoyancy effect, which causes the organoids to oscillate, complicating culture manipulation and rendering multiple handling steps difficult.Due to these challenges, most adipose spheroid and organoid models are scaffold-based, despite many cell types' ability to secrete extracellular matrix (ECM) components and self-assemble into aggregates. Scaffold-free 3D organoids have been less explored. To address the shortage of affordable and reliable AT models, we utilized magnetic bioprinting technology to develop a human-derived 3D model of adipose tissue. This system incorporates a magnetic holder that restrains organoids, preventing them from floating and minimizing the risk of loss during manipulation.This study outlines a protocol for generating In vitro AT-derived organoid using 3D magnetic bioprinting, with a focus on manufacturing, culturing, and assessing the morpho-functional characteristics of late-stage AT organoids. Magnetic bioprinting allows for the replication of tissue structure and function In vitro without the risk of organoid loss, making it an ideal method for high-throughput AT organoid culture. Additionally, the combination of 3D scaffold-free manufacturing with In vitro disease modeling offers a valuable tool for discovering treatments for metabolic diseases such as obesity and T2D.http://www.sciencedirect.com/science/article/pii/S2472555225000115Humanized, Adipose Tissue OrganoidsMagnetic BioprintingScaffold-Free ModelsAdipocyte DifferentiationMetabolic Disease Modeling |
| spellingShingle | Rafael Dariolli Raphael Nir Tova Mushlam Glauco R. Souza Stephen R. Farmer Miguel L Batista, Jr. Optimized scaffold-free human 3D adipose tissue organoid culture for obesity and disease modeling SLAS Discovery Humanized, Adipose Tissue Organoids Magnetic Bioprinting Scaffold-Free Models Adipocyte Differentiation Metabolic Disease Modeling |
| title | Optimized scaffold-free human 3D adipose tissue organoid culture for obesity and disease modeling |
| title_full | Optimized scaffold-free human 3D adipose tissue organoid culture for obesity and disease modeling |
| title_fullStr | Optimized scaffold-free human 3D adipose tissue organoid culture for obesity and disease modeling |
| title_full_unstemmed | Optimized scaffold-free human 3D adipose tissue organoid culture for obesity and disease modeling |
| title_short | Optimized scaffold-free human 3D adipose tissue organoid culture for obesity and disease modeling |
| title_sort | optimized scaffold free human 3d adipose tissue organoid culture for obesity and disease modeling |
| topic | Humanized, Adipose Tissue Organoids Magnetic Bioprinting Scaffold-Free Models Adipocyte Differentiation Metabolic Disease Modeling |
| url | http://www.sciencedirect.com/science/article/pii/S2472555225000115 |
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