PDF(Pubmed)
Abstract：
Patient-derived cancer organoids (PDOs) hold considerable promise for personalizing therapy selection and improving patient outcomes. However, it is challenging to generate PDOs in sufficient numbers to test therapies in standard culture platforms. This challenge is particularly acute for pancreatic ductal adenocarcinoma (PDAC) where most patients are diagnosed at an advanced stage with non-resectable tumors and where patient tissue is in the form of needle biopsies. Here the development and characterization of microfluidic devices for testing therapies using a limited amount of tissue or PDOs available from PDAC biopsies is described. It is demonstrated that microfluidic PDOs are phenotypically and genotypically similar to the gold-standard Matrigel organoids with the advantages of 1) spheroid uniformity, 2) minimal cell number requirement, and 3) not relying on Matrigel. The utility of microfluidic PDOs is proven by testing PDO responses to several chemotherapies, including an inhibitor of glycogen synthase kinase (GSKI). In addition, microfluidic organoid cultures are used to test effectiveness of immunotherapy comprised of NK cells in combination with a novel biologic. In summary, our microfluidic device offers considerable benefits for personalizing oncology based on cancer biopsies and may, in the future, be developed into a companion diagnostic for chemotherapy or immunotherapy treatments.
摘要：
患者来源的癌症类器官（PDO）在个性化治疗选择和改善患者预后方面具有广阔的前景。然而,在标准培养平台中生成足够数量的PDO来测试治疗是具有挑战性的。这种挑战对于胰腺导管腺癌（PDAC）尤其严重，其中大多数患者在晚期被诊断为不可切除的肿瘤，并且患者组织呈针状活检的形式。这里描述了使用可从PDAC活检获得的有限量的组织或PDO来测试治疗的微流体装置的开发和表征。已证明，微流体PDO在表型和基因型上与金标准Matrigel类器官相似，具有1）球体均匀性的优点，2）最小的细胞数量要求，和3）不依赖Matrigel。通过测试PDO对几种化疗的反应，证明了微流体PDO的实用性。包括糖原合成酶激酶（GSKI）的抑制剂。此外,微流控类器官培养物用于测试由NK细胞与新型生物制剂组合组成的免疫疗法的有效性。总之,我们的微流控设备提供了相当大的好处，用于基于癌症活检的个性化肿瘤学，在未来,被开发成用于化学疗法或免疫疗法治疗的伴随诊断。
