Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Department of Pharmaceutical Sciences, Center for Biomolecular Science, University of Illinois at Chicago, Chicago, IL 60607, USA.
Lab Chip. 2023 Nov 7;23(22):4821-4833. doi: 10.1039/d3lc00378g.
To accurately phenocopy human biology , researchers have been reducing their dependence on standard, static two-dimensional (2D) cultures and instead are moving towards three-dimensional (3D) and/or multicellular culture techniques. While these culture innovations are becoming more commonplace, there is a growing body of research that illustrates the benefits and even necessity of recapitulating the dynamic flow of nutrients, gas, waste exchange and tissue interactions that occur . However, cost and engineering complexity are two main factors that hinder the adoption of these technologies and incorporation into standard laboratory workflows. We developed LATTICE, a plug-and-play microfluidic platform able to house up to eight large tissue or organ models that can be cultured individually or in an interconnected fashion. The functionality of the platform to model both healthy and diseased tissue states was demonstrated using 3D cultures of reproductive tissues including murine ovarian tissues and human fallopian tube explants (hFTE). When exogenously exposed to pathological doses of gonadotropins and androgens to mimic the endocrinology of polycystic ovarian syndrome (PCOS), subsequent ovarian follicle development, hormone production and ovulation copied key features of this endocrinopathy. Further, hFTE cilia beating decreased significantly only when experiencing continuous media exchanges. We were then able to endogenously recreate this phenotype on the platform by dynamically co-culturing the PCOS ovary and hFTE. LATTICE was designed to be customizable with flexibility in 3D culture formats and can serve as a powerful automated tool to enable the study of tissue and cellular dynamics in health and disease in all fields of research.
为了准确地模拟人类生物学,研究人员一直在减少对标准静态二维(2D)培养的依赖,转而采用三维(3D)和/或多细胞培养技术。虽然这些培养创新越来越普遍,但越来越多的研究表明,重现发生的营养物质、气体、废物交换和组织相互作用的动态流动具有重要意义,甚至是必要的。然而,成本和工程复杂性是阻碍这些技术采用和纳入标准实验室工作流程的两个主要因素。我们开发了 LATTICE,这是一个即插即用的微流控平台,能够容纳多达 8 个大型组织或器官模型,可以单独或相互连接进行培养。该平台的功能是通过包括小鼠卵巢组织和人输卵管外植体(hFTE)在内的 3D 生殖组织培养来模拟健康和患病组织状态。当外源性暴露于模拟多囊卵巢综合征(PCOS)内分泌的病理剂量的促性腺激素和雄激素时,随后的卵巢卵泡发育、激素产生和排卵复制了这种内分泌失调的关键特征。此外,只有当 hFTE 纤毛持续进行介质交换时,纤毛的拍打才会显著减少。然后,我们能够通过在平台上动态共培养 PCOS 卵巢和 hFTE 来重现这种表型。LATTICE 设计具有 3D 培养格式的灵活性,可作为一种强大的自动化工具,用于研究健康和疾病状态下所有研究领域的组织和细胞动力学。