Dariolli Rafael, Nir Raphael, Mushlam Tova, Souza Glauco R, Farmer Stephen R, Batista Miguel L
Bonds Biosystems, 27 Strathmore Rd, Natick, MA, USA.
SBH, 27 Strathmore Rd, Natick, MA, USA.
SLAS Discov. 2025 Mar;31:100218. doi: 10.1016/j.slasd.2025.100218. Epub 2025 Jan 25.
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.
肥胖症和2型糖尿病（T2D）与异常的脂肪细胞代谢及脂肪组织（AT）功能障碍密切相关。然而，现有的脂肪组织模型存在局限性，尤其是在稳定培养维持生理相关表型的脂肪细胞方面，这阻碍了对脂肪细胞生物学及其分化背后分子机制的深入理解。当前的模型系统无法完全复制体内代谢，给脂肪组织研究带来了挑战。三维（3D）脂肪组织类器官尽管前景广阔，但在长期培养过程中面临重大的操作挑战。随着脂肪细胞成熟并积累脂肪，它们会形成器官样特征，增加浮力效应，导致类器官振荡，使培养操作复杂化，并使多个处理步骤变得困难。由于这些挑战，尽管许多细胞类型有能力分泌细胞外基质（ECM）成分并自组装成聚集体，但大多数脂肪球和类器官模型都是基于支架的。无支架3D类器官的研究较少。为了解决经济实惠且可靠的脂肪组织模型短缺的问题，我们利用磁性生物打印技术开发了一种人源化的3D脂肪组织模型。该系统包含一个磁性固定器，可限制类器官，防止它们漂浮，并将操作过程中的损失风险降至最低。本研究概述了一种使用3D磁性生物打印生成体外脂肪组织来源类器官的方案，重点在于制造、培养和评估晚期脂肪组织类器官的形态功能特征。磁性生物打印能够在体外复制组织结构和功能，且不存在类器官丢失的风险使其成为高通量脂肪组织类器官培养的理想方法。此外，3D无支架制造与体外疾病建模相结合，为发现肥胖症和T2D等代谢性疾病的治疗方法提供了有价值的工具。
