Sci Rep:研究人员培养出新的胰腺肿瘤模型,为新药测试提供更多可能性

2021-01-23 MedSci原创 MedSci原创

胰腺导管腺癌(PDAC)预后不良的原因是间质纤维化严重,且多细胞微环境复杂,临床前模型难以完全重现。研究人员旨在开发一个完整的能维持生存、拥有三维多细胞结构和且能提供微环境线索的组织离体外植体模型,来

胰腺导管腺癌(PDAC)预后不良的原因是间质纤维化严重,且多细胞微环境复杂,临床前模型难以完全重现。研究人员旨在开发一个完整的能维持生存、拥有三维多细胞结构和且能提供微环境线索的组织离体外植体模型,来实现快速转换治疗方法并为个体化医学提供信息的目的。

研究人员将来自患者手术切除的PDAC组织被切割成1-2mm的外植体,在明胶海绵上进行培养。免疫组化显示,人PDAC外植体共存活了12天,并保持其原有的肿瘤、基质和细胞外基质结构。作为原理论证,他们用Abraxane(药品主要成分为人白蛋白结合型紫杉醇,目前用于PDAC17一线治疗的化疗药物之一PDAC外植体进行处理,每隔3天向培养基中加入0.3μg/mL或4.2μg/mL的Abraxane,第12天固定外植体,然后进行TUNEL染色以评估细胞死亡情况,并观察了不同患者来源的外植体不同程度的反应。同时,他们还使用聚合物纳米粒子 + Cy5 siRNA对PDAC外植体进行转染,发现Cy5 siRNA在整个PDAC外植体中存在大量细胞质分布。

外植体培养

使用QuPath对TUNEL(细胞凋亡检测试剂)阳性细胞的定量显示,与未经处理的对照组相比,Abraxane处理的外植体中的细胞死亡增加。

该团队的模型保留了人PDAC的3D结构,和标准的类器官相比具有很多优势,说明这一方法在测试不同药物对癌症的影响以及为后续患者提供个性化的药物治疗方面具有巨大潜力,为研究PDAC生物学(包括肿瘤-间质相互作用)和快速评估治疗反应以推动个性化治疗提供了前所未有的机会。

团队人员表示,他们还需要解决该模型的一个局限性就是——他们只研究了接受过手术的患者的肿瘤,而这大约仅占胰腺癌患者的15%到20%,因为绝大多数患者的肿瘤不能通过手术切除。因此他们还想从有转移性疾病的患者身上获取肿瘤样本好帮助所有的胰腺癌患者。

原始出处:John Kokkinos, George Sharbeen, Koroush S. Haghighi, et al.  Ex vivo culture of intact human patient derived pancreatic tumour tissue.  Sci Rep. 21 January 2021

 

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    2021-01-23 CHANGE

    梅斯里提供了很多疾病的模型计算公式,赞一个!

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