Arai Shunya, Miyauchi Masashi, Kurokawa Mineo
Department of Hematology & Oncology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku; and CREST, Japan Science and Technology Agency, Chiyoda-ku, Tokyo, Japan.
Department of Hematology & Oncology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku; and CREST, Japan Science and Technology Agency, Chiyoda-ku, Tokyo, Japan.
Exp Hematol. 2015 Aug;43(8):654-60. doi: 10.1016/j.exphem.2015.06.006. Epub 2015 Jun 29.
Induced pluripotent stem cells (iPSCs) can be generated from various types of cells with transduction of defined transcription factors. Patient-derived iPSCs are becoming commonly utilized for understanding the molecular pathways involved in disease and for the development of novel targeted therapies. With the use of patient-derived iPSCs differentiated to specific-lineage cells, the potency and toxicity of drug candidates can be evaluated. In the past, patient-derived iPSCs were mainly established from patients of inherited hematologic diseases, followed by the expansion of target to acquired diseases like myeloproliferative neoplasms. Thanks to the rapid development of novel genome editing technologies, we can now utilize genetically modified and unprocessed iPSCs more readily than before. These technologies, which enable us to modulate genetic status or even chromosome structure at the right time, could help the elucidation of pathogenesis of hematologic diseases. If iPSC-derived hematopoietic cells are to be robustly reconstituted in vivo as a consequence of the development of reprogramming and conversion technology, research on leukemic stem cells must be widely promoted. Therefore, iPSC technology has great potential on oncology research using patient samples.
通过转导特定转录因子,可从多种类型的细胞中生成诱导多能干细胞(iPSC)。患者来源的iPSC正越来越普遍地用于了解疾病相关的分子途径以及开发新型靶向疗法。利用患者来源的iPSC分化为特定谱系细胞,可以评估候选药物的效力和毒性。过去,患者来源的iPSC主要从遗传性血液病患者中建立,随后将目标扩展到骨髓增殖性肿瘤等获得性疾病。得益于新型基因组编辑技术的快速发展,我们现在比以往更易于利用基因修饰和未处理的iPSC。这些技术使我们能够在适当的时候调节基因状态甚至染色体结构,有助于阐明血液系统疾病的发病机制。如果由于重编程和转化技术的发展,iPSC衍生的造血细胞能够在体内得到有力重建,那么白血病干细胞的研究必须广泛推进。因此,iPSC技术在使用患者样本进行肿瘤学研究方面具有巨大潜力。