Seitlinger Joseph, Nounsi Anasse, Idoux-Gillet Ysia, Santos Pujol Eloy, Lê Hélène, Grandgirard Erwan, Olland Anne, Lindner Véronique, Zaupa Cécile, Balloul Jean-Marc, Quemeneur Eric, Massard Gilbert, Falcoz Pierre-Emmanuel, Hua Guoqiang, Benkirane-Jessel Nadia
INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine, CRBS, 1 Rue Eugène Boeckel, 67000 Strasbourg, France.
1 Place de l'Hôpital, University Hospital Strasbourg (HUS), 67000 Strasbourg, France.
Biomedicines. 2022 May 10;10(5):1103. doi: 10.3390/biomedicines10051103.
Patient-derived tumoroid (PDT) has been developed and used for anti-drug screening in the last decade. As compared to other existing drug screening models, a PDT-based in vitro 3D cell culture model could preserve the histological and mutational characteristics of their corresponding tumors and mimic the tumor microenvironment. However, few studies have been carried out to improve the microvascular network connecting the PDT and its surrounding microenvironment, knowing that poor tumor-selective drug transport and delivery is one of the major reasons for both the failure of anti-cancer drug screens and resistance in clinical treatment. In this study, we formed vascularized PDTs in six days using multiple cell types which maintain the histopathological features of the original cancer tissue. Furthermore, our results demonstrated a vascular network connecting PDT and its surrounding microenvironment. This fast and promising PDT model opens new perspectives for personalized medicine: this model could easily be used to test all therapeutic treatments and could be connected with a microfluidic device for more accurate drug screening.
患者来源的类肿瘤(PDT)在过去十年中得到了发展并用于抗药物筛选。与其他现有的药物筛选模型相比,基于PDT的体外3D细胞培养模型可以保留其相应肿瘤的组织学和突变特征,并模拟肿瘤微环境。然而,尽管已知肿瘤选择性药物转运和递送不佳是抗癌药物筛选失败和临床治疗耐药的主要原因之一,但很少有研究致力于改善连接PDT及其周围微环境的微血管网络。在本研究中,我们使用多种细胞类型在六天内形成了血管化的PDT,这些细胞类型保持了原始癌组织的组织病理学特征。此外,我们的结果证明了连接PDT及其周围微环境的血管网络。这种快速且有前景的PDT模型为个性化医学开辟了新的前景:该模型可轻松用于测试所有治疗方法,并可与微流控设备连接以进行更精确的药物筛选。