Patient-derived induced pluripotent stem cells in cancer research and precision oncology

Abstract

Together with recent advances in the processing and culture of human tissue, bioengineering, xenotransplantation and genome editing, Induced pluripotent stem cells (iPSCs) present a range of new opportunities for the study of human cancer. Here we discuss the main advantages and limitations of iPSC modeling, and how the method intersects with other patient-derived models of cancer, such as organoids, organson-chips and patient-derived xenografts (PDXs). We highlight the opportunities that iPSC models can provide beyond those offered by existing systems and animal models and present current challenges and crucial areas for future improvements toward wider adoption of this technology.

Stage-Specific Human Induced Pluripotent Stem Cells Map the Progression of Myeloid Transformation to Transplantable Leukemia

“…It might be possible to overcome this refractoriness by using alternative reprogramming factor cocktails, which we did not test here. A negative or positive impact of specific cancer-associated gene mutations on the reprogramming “fitness” of the cells would not be surprising given well-studied positive and negative effects, respectively, of TP53 inactivation and Fanconi Anemia pathway mutations on reprogramming (Papapetrou, 2016). Importantly, despite the skewed clonal and subclonal representation, we were able to capture normal and preleukemic cells, as well as malignant clones and subclones and thus compile a panel of lines carrying genomes representative of different disease stages from normal to fully transformed states.…”

ASXL3 Is a Novel Pluripotency Factor in Human Respiratory Epithelial Cells and a Potential Therapeutic Target in Small Cell Lung Cancer

“…iPSC exhibit numerous similarities to embryonic stem cells (ESCs) including morphology, gene expression profiles, in-vitro proliferation, and in-vivo teratoma formation (13, 16). As such, iPSC have emerged as important models with which to study epigenetic mechanisms contributing to pluripotency in normal cells, as well as stemness, chemo-resistance and metastatic phenotypes of cancer cells (17). …”

Targeting the Hedgehog Signaling Pathway by Glasdegib Limits the Self- Renewal of MDS-Derived Induced Potent Stem Cells (iPSC)

“…In vitro modeling of human disease has been greatly facilitated by iPSCs technologies [8,13]. Characterized by their ability to self-renew indefinitely and differentiate into various cell lineages, iPSCs provide a powerful system for human disease modeling [8,13]. In the present study, we established iPSCs from an MDS patient.…”

“…The identification of distinct human CSCs exerting their potential in patients, including in MDS, has remain elusive [2,3]. In vitro modeling of human disease has been greatly facilitated by iPSCs technologies [8,13]. Characterized by their ability to self-renew indefinitely and differentiate into various cell lineages, iPSCs provide a powerful system for human disease modeling [8,13].…”

“…In vitro clonogenic growth upon serial re-plating, secondary colony formations were significantly inhibited by hedgehog pathway inhibitors. These results suggested that the hedgehog inhibitors may become extremely useful therapeutic interventions in a number of hematological neoplasms, including MDS, where the persistence of cancer stem cells [13,14].…”