Liu Wei, Ju Lingao, Cheng Songtao, Wang Gang, Qian Kaiyu, Liu Xuefeng, Xiao Yu, Wang Xinghuan
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.
Clin Transl Med. 2020 Jun;10(2):e95. doi: 10.1002/ctm2.95. Epub 2020 Jun 5.
Patient-derived models, including cell models (organoids and conditionally reprogrammed cells [CRCs]) and patient-derived xenografts, are urgently needed for both basic and translational cancer research. Conditional reprogramming (CR) technique refers to a co-culture system of primary human normal or tumor cells with irradiated murine fibroblasts in the presence of a Rho-associated kinase inhibitor to allow the primary cells to acquire stem cell properties and the ability to proliferate indefinitely in vitro without any exogenous gene or viral transfection. Considering its robust features, the CR technique may facilitate cancer research in many aspects. Under in vitro culturing, malignant CRCs can share certain genetic aberrations and tumor phenotypes with their parental specimens. Thus, tumor CRCs can promisingly be utilized for the study of cancer biology, the discovery of novel therapies, and the promotion of precision medicine. For normal CRCs, the characteristics of normal karyotype maintenance and lineage commitment suggest their potential in toxicity testing and regenerative medicine. In this review, we discuss the applications, limitations, and future potential of CRCs in modeling urological cancer and translation to clinics.
患者来源的模型，包括细胞模型（类器官和条件重编程细胞[CRCs]）以及患者来源的异种移植，对于基础癌症研究和转化癌症研究都至关重要。条件重编程（CR）技术是指在存在Rho相关激酶抑制剂的情况下，将原代人正常或肿瘤细胞与经辐照的小鼠成纤维细胞进行共培养，以使原代细胞获得干细胞特性并在体外无限增殖的能力，而无需任何外源基因或病毒转染。鉴于其强大的特性，CR技术可能在许多方面促进癌症研究。在体外培养条件下，恶性CRCs可与其亲代标本共享某些基因畸变和肿瘤表型。因此，肿瘤CRCs有望用于癌症生物学研究、新疗法的发现以及精准医学的推广。对于正常CRCs，正常核型维持和谱系定向的特征表明它们在毒性测试和再生医学中的潜力。在本综述中，我们讨论了CRCs在泌尿系统癌症建模及向临床转化中的应用、局限性和未来潜力。
