Department of Clinical Analysis, Toxicology and Food Science, School of Pharmaceutical Sciences, University of São Paulo (USP), Ribeirão Preto, São Paulo 14040-903, Brazil.
Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX 77054, USA.
J Cell Sci. 2018 Feb 21;131(4):jcs203018. doi: 10.1242/jcs.203018.
Although hematopoietic stem cell (HSC) therapy for hematological diseases can lead to a good outcome from the clinical point of view, the limited number of ideal donors, the comorbidity of patients and the increasing number of elderly patients may limit the application of this therapy. HSCs can be generated from induced pluripotent stem cells (iPSCs), which requires the understanding of the bone marrow and liver niches components and function iPSCs have been extensively applied in several studies involving disease models, drug screening and cellular replacement therapies. However, the somatic reprogramming by transcription factors is a low-efficiency process. Moreover, the reprogramming process is also regulated by microRNAs (miRNAs), which modulate the expression of the transcription factors OCT-4 (also known as POU5F1), SOX-2, KLF-4 and MYC, leading somatic cells to a pluripotent state. In this Review, we present an overview of the challenges of cell reprogramming protocols with regard to HSC generation from iPSCs, and highlight the potential role of miRNAs in cell reprogramming and in the differentiation of induced pluripotent stem cells.
虽然造血干细胞(HSC)疗法可从临床角度治疗血液疾病,但由于理想供体数量有限、患者合并症以及老年患者人数不断增加,可能限制了该疗法的应用。诱导多能干细胞(iPSC)可生成 HSC,这需要深入了解骨髓和肝脏龛位的组成和功能。iPSC 已广泛应用于涉及疾病模型、药物筛选和细胞替代疗法的多项研究中。然而,转录因子的体细胞重编程是一个低效率的过程。此外,重编程过程还受到 microRNAs(miRNAs)的调节,miRNAs 调节转录因子 OCT-4(也称为 POU5F1)、SOX-2、KLF-4 和 MYC 的表达,使体细胞进入多能状态。在本综述中,我们概述了从 iPSC 生成 HSC 的细胞重编程方案所面临的挑战,并强调了 miRNAs 在细胞重编程和诱导多能干细胞分化中的潜在作用。