Kouchaki Reza, Abd-Nikfarjam Bahareh, Maali Amir Hosein, Abroun Saeid, Foroughi Farshad, Ghaffari Sasan, Azad Mehdi
Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Department of Immunology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Cell J. 2020 Jul;22(suppl 1):1-10. doi: 10.22074/cellj.2020.6849. Epub 2020 Jul 18.
Severe combined immunodeficiency (SCID) is classified as a primary immunodeficiency, which is characterized by impaired T-lymphocytes differentiation. and (Artemis) are the most defective genes in SCID. The most recent SCID therapies are based on gene therapy (GT) of hematopoietic stem cells (HSC), which are faced with many challenges. The new studies in the field of stem cells have made great progress in overcoming the challenges ahead. In 2006, Yamanaka et al. achieved "reprogramming" technology by introducing four transcription factors known as Yamanaka factors, which generate induced pluripotent stem cells (iPSC) from somatic cells. It is possible to apply iPSC-derived HSC for transplantation in patients with abnormality or loss of function in specific cells or damaged tissue, such as T-cells and NK-cells in the context of SCID. The iPSC-based HSC transplantation in SCID and other hereditary disorders needs gene correction before transplantation. Furthermore, iPSC technology has been introduced as a promising tool in cellular-molecular disease modeling and drug discovery. In this article, we review iPSC-based GT and modeling for SCID disease and novel approaches of iPSC application in SCID.
重症联合免疫缺陷（SCID）被归类为原发性免疫缺陷，其特征是T淋巴细胞分化受损。ADA（腺苷脱氨酶）和ARTEMIS是SCID中缺陷最严重的基因。最新的SCID治疗方法基于造血干细胞（HSC）的基因治疗（GT），但面临诸多挑战。干细胞领域的新研究在克服这些挑战方面取得了巨大进展。2006年，山中伸弥等人通过引入四种被称为山中因子的转录因子实现了“重编程”技术，该技术可从体细胞产生诱导多能干细胞（iPSC）。将iPSC衍生的HSC应用于特定细胞异常或功能丧失或组织受损的患者进行移植成为可能，例如在SCID背景下的T细胞和NK细胞。在SCID和其他遗传性疾病中基于iPSC的HSC移植在移植前需要进行基因校正。此外，iPSC技术已被视为细胞分子疾病建模和药物发现中有前景的工具。在本文中，我们综述了基于iPSC的GT和SCID疾病建模以及iPSC在SCID中的新应用方法。
