Tulane University School of Medicine, New Orleans, Louisiana, USA.
LaCell LLC, New Orleans, Louisiana, USA.
Tissue Eng Part B Rev. 2020 Dec;26(6):586-595. doi: 10.1089/ten.TEB.2019.0261. Epub 2020 Dec 3.
The obesity epidemic and its associated comorbidities present a looming challenge to health care delivery throughout the world. Obesity is characterized as a sterile inflammatory process within adipose tissues leading to dysregulated secretion of bioactive adipokines such as adiponectin and leptin, as well as systemic metabolic dysfunction. The majority of current obesity research has focused primarily on preclinical animal models and two-dimensional cell culture models . Neither of these generalized approaches is optimal due to interspecies variability, insufficient accuracy with respect to predicting human outcomes, and failure to recapitulate the three-dimensional (3D) microenvironment. Consequently, there is a growing demand and need for more sophisticated microphysiological systems to reproduce more physiologically accurate human white and brown/beige adipose depots. To address this research need, human and murine cell lines and primary cultures are being combined with bioscaffolds to create functional 3D environments that are suitable for metabolically active adipose organoids in both static and perfusion bioreactor cultures. The development of these technologies will have considerable impact on the future pace of discovery for novel small molecules and biologics designed to prevent and treat metabolic syndrome and obesity in humans. Furthermore, when these adipose tissue models are integrated with other organ systems they will have applicability to obesity-related disorders such as diabetes, nonalcoholic fatty liver disease, and osteoarthritis. Impact statement The current review article summarizes the advances made within the organ-onchip field, as it pertains to adipose tissue models of obesity and obesity-related syndromes, such as diabetes, non-alcoholic fatty liver disease, and osteoarthritis. As humanized 3D adipose-derived constructs become more accessible to the research community, it is anticipated that they will accelerate and enhance the drug discovery pipeline for obesity, diabetes, and metabolic diseases by reducing the preclinical evaluation process and improving predictive accuracy. Such developments, applications, and usages of existing technologies can change the paradigm of personalized medicine and create substantial progress in our approach to modern medicine.
肥胖症的流行及其相关并发症对全球医疗服务的提供构成了迫在眉睫的挑战。肥胖症的特征是脂肪组织中无菌性炎症过程，导致生物活性脂肪因子如脂联素和瘦素的失调分泌，以及全身代谢功能障碍。目前大多数肥胖症研究主要集中在临床前动物模型和二维细胞培养模型上。由于种间变异性、预测人类结果的准确性不足以及未能再现三维（3D）微环境，这两种通用方法都不是最佳方法。因此，人们越来越需要更复杂的微生理系统来复制更符合生理条件的人类白色和棕色/米色脂肪组织。为了满足这一研究需求，人类和鼠类细胞系和原代培养物正在与生物支架结合，以创建适合静态和灌注生物反应器培养中代谢活跃的脂肪类器官的功能性 3D 环境。这些技术的发展将对未来发现用于预防和治疗人类代谢综合征和肥胖症的新型小分子和生物制剂的步伐产生重大影响。此外，当这些脂肪组织模型与其他器官系统集成时，它们将适用于与肥胖相关的疾病，如糖尿病、非酒精性脂肪性肝病和骨关节炎。 影响说明 本文综述了器官芯片领域在肥胖症和肥胖相关综合征（如糖尿病、非酒精性脂肪性肝病和骨关节炎）的脂肪组织模型方面的进展。随着人类化 3D 脂肪衍生构建体越来越容易被研究界获得，可以预期它们将通过减少临床前评估过程和提高预测准确性来加速和增强肥胖症、糖尿病和代谢疾病的药物发现管道。这些现有技术的发展、应用和使用可以改变个性化医学的范式，并在我们对现代医学的方法上取得重大进展。
