Induced Pluripotent Stem Cells and Induced Pluripotent Cancer Cells in Cancer Disease Modeling.

In 2006, Noble Prize laureate Shinya Yamanaka discovered that a set of transcription factors can reprogram terminally differentiated somatic cells to a pluripotent stem cell state. Since then, induced pluripotent stem cells (iPSCs) have come into the public spotlight. Amidst a growing field of promising clinical uses of iPSCs in recent years, cancer disease modeling has emerged as a particularly promising and rapidly translatable application of iPSCs. Technological advances in genome editing over the past few years have facilitated increasingly rapid progress in generation of iPSCs with clearly defined genetic backgrounds to complement existing patient-derived models. Improved protocols for differentiation of iPSCs, engineered iPSCs and embryonic stem cells (ESCs) now permit the study of disease biology in the majority of somatic cell types. Here, we highlight current efforts to create patient-derived iPSC disease models to study various cancer types. We review the advantages and current challenges of using iPSCs in cancer disease modeling.

Cancer in a dish: progress using stem cells as a platform for cancer research.

Cancer models derived from patient specimens poorly reflect early-stage cancer development because cancer cells acquire numerous additional molecular alterations before the disease is clinically detectable. Earlier studies have used differentiated cells derived from induced pluripotent cancer cells (iPCCs) to partially mirror cancer disease phenotype, but the highly heterogeneous nature of cancer cells as well as difficulties with reprogramming cancer cells has limited the application of this technique. An alternative approach to modeling cancer in a dish entails reprogramming adult differentiated cells from patients with cancer syndromes to pluripotent stem cells (PSCs), followed by directed differentiation of those PSCs. A directed reprogramming and differentiation strategy has the potential to recapitulate cancer progression and capture the earliest molecular alterations that underlie cancer initiation. The reprogrammed cells share patient-specific genetic and epigenetic traits, offering a new platform to develop personalized therapy for cancer patients. In this review, we will provide an overview of available reprogramming methods of cancer cells and describe how cancer-derived stem cells have been used to characterize effects of defined molecular alterations in specific cell types. We also describe the "disease in a dish" model developed to study genetic cancer syndromes. These approaches highlight recent contributions of stem cell technology to the cancer biology realm.

Establishment of a human embryonic stem cell line with homozygous TP53 R248W mutant by TALEN mediated gene editing.

Genetic mutations in TP53 contribute to multiple human cancers. Here we report the generation of a H1-p53(R248W/R248W) human embryonic stem cell line harboring a homozygous TP53 R248W mutation created by TALEN-mediated precise gene editing. The H1-p53(R248W/R248W) cell line maintains a normal karyotype, robust pluripotency gene expression, and the potential to differentiate to the three germ layers.