Modeling Hematological Diseases and Cancer With Patient-Specific Induced Pluripotent Stem Cells.

Huensuk Kim,Christoph Schaniel

doi:10.3389/fimmu.2018.02243

Huensuk Kim, Christoph Schaniel

Open Access

https://doi.org/10.3389/fimmu.2018.02243

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Abstract

The advent of induced pluripotent stem cells (iPSCs) together with recent advances in genome editing, microphysiological systems, tissue engineering and xenograft models present new opportunities for the investigation of hematological diseases and cancer in a patient-specific context. Here we review the progress in the field and discuss the advantages, limitations, and challenges of iPSC-based malignancy modeling. We will also discuss the use of iPSCs and its derivatives as cellular sources for drug target identification, drug development and evaluation of pharmacological responses.

Highlights

Hematological diseases and cancers are devastating diseases with a high economic and social burden
Isogenic normal induced pluripotent stem cells (iPSCs) can be established independently through a separate reprogramming experiment with somatic cells obtained from a non-malignant area adjacent to the tumor, a biopsy from an unaffected tissue such as the skin or from blood in the case of non-hematological disorders or cancers [33, 82]. Another advantage of the iPSC technology is that reprogramming of malignant cells might establish iPSCs that represent various stages of disease progression, as cancers are often associated with serial accumulation of specific malignant mutations/lesions
It is noteworthy though that the majority of Apc-iPSCderived colonic legions remained in a pretumoral microadenoma stage and did not develop into full blown macroscopic colon tumors. These findings imply that disease cell properties and biological consequences of tumor-causing mutations are strongly depending on the cellular context and underscore that epigenetic regulation, which is critical for cell fate determination and fixing the malignant cell state in cancer, exerts great influence on disease development and progression

Summary

Introduction

Hematological diseases and cancers are devastating diseases with a high economic and social burden. One of the main advantages of the iPSC technology is that hematological disease-associated and malignant lesions can be studied with human cells and in the genomic context of the patient.

Results

Conclusion