肥胖和2型糖尿病正在成为全球社会医学负担。棕色脂肪细胞正逐渐成为关键的可诱导性因子和潜在的改善代谢健康的治疗靶点。然而，目前缺乏人体棕色脂肪组织的体外模型，阻碍了对这种细胞类型和生物治疗的研究。与旨在生成构建模块的传统自下而上的工程方法不同，这里提出了一种可伸缩系统，利用白色脂肪组织的人体基质血管组分作为脂肪和内皮细胞前体的来源，生成具有预先血管化和功能的人体棕色脂肪组织器官样体。这种工程方法利用定义的生物力学和化学环境，通过抑制肿瘤生长因子β（TGFβ）途径和特定的明胶甲丙烯酰（GelMA）嵌入参数，促进GelMA水凝胶中球体的自组织形成，从而促进棕色脂肪生成和血管生成。结果显示，这种血管化器官样体具有原始棕色脂肪组织的关键特征，包括可诱导抗偶联蛋白-1（UCP1）表达、增加的非偶联线粒体呼吸和棕色脂肪素分泌。球体的可控组装使得器官样体形态发生可以从宏观尺度上进行转化，生成血管化的厘米尺度的棕色脂肪微组织。这种方法在开发体外人体棕色脂肪组织模型方面具有重要的进展，并有助于从基础研究到生物治疗的广泛应用。© 2023 年 Wiley-VCH GmbH. Advanced Science出版。

Obesity and type 2 diabetes are becoming a global sociobiomedical burden. Beige adipocytes are emerging as key inducible actors and putative relevant therapeutic targets for improving metabolic health. However, in vitro models of human beige adipose tissue are currently lacking and hinder research into this cell type and biotherapy development. Unlike traditional bottom-up engineering approaches that aim to generate building blocks, here a scalable system is proposed to generate pre-vascularized and functional human beige adipose tissue organoids using the human stromal vascular fraction of white adipose tissue as a source of adipose and endothelial progenitors. This engineered method uses a defined biomechanical and chemical environment using tumor growth factor β (TGFβ) pathway inhibition and specific gelatin methacryloyl (GelMA) embedding parameters to promote the self-organization of spheroids in GelMA hydrogel, facilitating beige adipogenesis and vascularization. The resulting vascularized organoids display key features of native beige adipose tissue including inducible Uncoupling Protein-1 (UCP1) expression, increased uncoupled mitochondrial respiration, and batokines secretion. The controlled assembly of spheroids allows to translate organoid morphogenesis to a macroscopic scale, generating vascularized centimeter-scale beige adipose micro-tissues. This approach represents a significant advancement in developing in vitro human beige adipose tissue models and facilitates broad applications ranging from basic research to biotherapies.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.