Martinez Alba, Buckley Molly S, Scalise Carly B, Wang Dezhi, Katre Ashwini A, Birrer Michael J, Berry Joel L, Arend Rebecca C
Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA.
J Tissue Eng. 2021 Nov 17;12:20417314211055015. doi: 10.1177/20417314211055015. eCollection 2021 Jan-Dec.
Among gynecologic malignancies, ovarian cancer (OC) has the poorest survival rate, and its clinical management remains challenging due to the high rate of recurrence and chemoresistance. Improving survival for these patients is critical, although this requires the ability to translate preclinical studies to actual patient care: bench to bedside and back. Our objective was to develop a preclinical model that accurately represents tumor biology and its microenvironment. We utilized SKOV-3, OVCAR-8, and CS-99 cell lines to show that this model was suitable for in vitro assessment of cell proliferation. We tested OC cells independently and in co-culture with cancer associated fibroblasts (CAFs) or immune cells. Additionally, we used patient-derived ovarian carcinoma and carcinosarcoma samples to show that the system maintains the histologic morphology of the primary tissue after 7 days. Moreover, we tested the response to chemotherapy using both cell lines and patient-derived tumor specimens and confirmed that cell death was significantly higher in the treated group compared to the vehicle group. Finally, we immune profiled the 3-D model containing patient tissue after several days in the bioreactor system and revealed that the immune populations are still present. Our data suggest that this model is a suitable preclinical model to aid in research that will ultimately impact the treatment of patients with gynecologic cancer.
在妇科恶性肿瘤中，卵巢癌（OC）的生存率最低，由于其高复发率和化疗耐药性，其临床管理仍然具有挑战性。提高这些患者的生存率至关重要，尽管这需要将临床前研究转化为实际患者护理的能力：从实验台到病床再回归。我们的目标是建立一个能够准确代表肿瘤生物学及其微环境的临床前模型。我们利用SKOV-3、OVCAR-8和CS-99细胞系来表明该模型适用于细胞增殖的体外评估。我们分别测试了OC细胞，并将其与癌症相关成纤维细胞（CAFs）或免疫细胞共培养。此外，我们使用患者来源的卵巢癌和癌肉瘤样本表明，该系统在7天后仍能维持原发组织的组织学形态。此外，我们使用细胞系和患者来源的肿瘤标本测试了对化疗的反应，并证实与载体组相比，治疗组的细胞死亡显著更高。最后，我们在生物反应器系统中对含有患者组织的三维模型进行了几天后的免疫分析，发现免疫群体仍然存在。我们的数据表明，该模型是一个合适的临床前模型，有助于开展最终影响妇科癌症患者治疗的研究。
