Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA; Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, San Francisco, California, USA.
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA; Neurosurgery and Brain Tumor Research Center, University of California, San Francisco, San Francisco, California, USA.
CRISPR J. 2022 Aug;5(4):517-535. doi: 10.1089/crispr.2022.0032.
Advances in genome and tissue engineering have spurred significant progress and opportunity for innovation in cancer modeling. Human induced pluripotent stem cells (iPSCs) are an established and powerful tool to study cellular processes in the context of disease-specific genetic backgrounds; however, their application to cancer has been limited by the resistance of many transformed cells to undergo successful reprogramming. Here, we review the status of human iPSC modeling of solid tumors in the context of genetic engineering, including how base and prime editing can be incorporated into "bottom-up" cancer modeling, a term we coined for iPSC-based cancer models using genetic engineering to induce transformation. This approach circumvents the need to reprogram cancer cells while allowing for dissection of the genetic mechanisms underlying transformation, progression, and metastasis with a high degree of precision and control. We also discuss the strengths and limitations of respective engineering approaches and outline experimental considerations for establishing future models.
基因组和组织工程的进步为癌症建模的创新带来了重大进展和机遇。人类诱导多能干细胞（iPSC）是研究特定疾病遗传背景下细胞过程的一种成熟而强大的工具；然而，它们在癌症中的应用受到许多转化细胞对成功重编程的抵抗力的限制。在这里，我们回顾了遗传工程背景下人类 iPSC 对实体瘤的建模现状，包括碱基编辑和 Prime 编辑如何被整合到“自下而上”的癌症建模中，我们将其用于使用遗传工程诱导转化的基于 iPSC 的癌症模型。这种方法避免了对癌细胞进行重新编程的需要，同时允许高度精确和控制地解析转化、进展和转移的遗传机制。我们还讨论了各自工程方法的优缺点，并概述了建立未来模型的实验注意事项。
