Chen Qiong, Wang Jing, Li Wenzhao, Shang Luoran, Wang Dexuan, Duan Ping
Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
Oncology Discipline Group, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
Adv Sci (Weinh). 2025 May;12(20):e2504647. doi: 10.1002/advs.202504647. Epub 2025 Apr 28.
Endometriosis (EMs), a significant global health issue, characterized by unclear pathogenesis, nonspecific symptoms, and poor treatment outcomes. The organ-on-chip technology has achieved great advances in disease modeling, yet its potential in EMs-related research remains largely untapped. Herein, a microfluidic chip platform that integrates primary cell-laden microcapsules for personalized drug evaluation. Specifically, primary human ectopic endometrial stromal cells (hESCs) within microcapsules featuring a biocompatible carboxymethyl cellulose (CMC) core and a stable alginate (ALG) shell using precise microfluidic electrospray are encapsulated. These microcapsules are integrated into a chip with a branched gradient generator and multiple cell-culture chambers, enabling tailored and high-throughput drug screening. By exposing hESCs-microcapsules derived from primary cells of distinct patient individuals to various drugs on-chip, significant inter-individual variability was revealed, with a strong correlation to clinical outcomes. This unique combination of patient-specific 3D microenvironments and dynamic drug gradient control represents a paradigm shift in personalized EMs research. Further integrating with omics techniques, its capability in exploring promising drugs is showcased. These results reveal that the chip platform could deliver dependable and personalized drug screening outcomes, thereby benefiting both scientific inquiries and clinical therapies.
子宫内膜异位症(EMs)是一个重大的全球健康问题,其发病机制不明,症状不具特异性,治疗效果不佳。器官芯片技术在疾病建模方面取得了巨大进展,但其在子宫内膜异位症相关研究中的潜力在很大程度上仍未得到开发。在此,我们构建了一个微流控芯片平台,该平台集成了负载原代细胞的微胶囊用于个性化药物评估。具体而言,使用精确的微流控电喷雾技术,将原代人异位子宫内膜基质细胞(hESCs)包裹在具有生物相容性羧甲基纤维素(CMC)核心和稳定海藻酸盐(ALG)外壳的微胶囊中。这些微胶囊被集成到一个带有分支梯度发生器和多个细胞培养室的芯片中,能够进行定制化和高通量药物筛选。通过在芯片上使来自不同患者个体原代细胞的hESCs微胶囊暴露于各种药物,发现了显著的个体间差异,且与临床结果具有很强的相关性。这种患者特异性三维微环境与动态药物梯度控制的独特结合代表了个性化子宫内膜异位症研究的范式转变。进一步与组学技术整合,展示了其在探索有前景药物方面的能力。这些结果表明,该芯片平台能够提供可靠且个性化的药物筛选结果,从而有益于科学研究和临床治疗。