Epah Jeremy, Schäfer Richard
Institute for Transfusion Medicine and Immunohaematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH, Goethe University Hospital, Frankfurt am Main, Germany.
Gene Ther. 2021 Sep;28(9):528-541. doi: 10.1038/s41434-021-00229-x. Epub 2021 Feb 15.
Hematopoietic stem cell transplantation (HSCT) is the therapeutic concept to cure the blood/immune system of patients suffering from malignancies, immunodeficiencies, red blood cell disorders, and inherited bone marrow failure syndromes. Yet, allogeneic HSCT bear considerable risks for the patient such as non-engraftment, or graft-versus host disease. Transplanting gene modified autologous HSCs is a promising approach not only for inherited blood/immune cell diseases, but also for the acquired immunodeficiency syndrome. However, there is emerging evidence for substantial heterogeneity of HSCs in situ as well as ex vivo that is also observed after HSCT. Thus, HSC gene modification concepts are suggested to consider that different blood disorders affect specific hematopoietic cell types. We will discuss the relevance of HSC heterogeneity for the development and manufacture of gene therapies and in exemplary diseases with a specific emphasis on the key target HSC types myeloid-biased, lymphoid-biased, and balanced HSCs.
造血干细胞移植（HSCT）是一种治疗理念，旨在治愈患有恶性肿瘤、免疫缺陷、红细胞疾病和遗传性骨髓衰竭综合征的患者的血液/免疫系统。然而，异基因HSCT对患者存在相当大的风险，如植入失败或移植物抗宿主病。移植基因修饰的自体造血干细胞不仅对遗传性血液/免疫细胞疾病，而且对获得性免疫缺陷综合征都是一种有前景的方法。然而，有新的证据表明，原位和体外的造血干细胞都存在显著的异质性，这种异质性在HSCT后也能观察到。因此，造血干细胞基因修饰概念建议考虑不同的血液疾病会影响特定的造血细胞类型。我们将讨论造血干细胞异质性在基因治疗开发和制造中的相关性，并以特定的关键目标造血干细胞类型——髓系偏向性、淋巴系偏向性和平衡造血干细胞为例，探讨相关疾病。
