Department of Medicine, Center for Regenerative Medicine (CReM), Boston University School of Medicine, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA; Section of Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Department of Medicine, Center for Regenerative Medicine (CReM), Boston University School of Medicine, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA; Section of Hematology-Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Stem Cell Reports. 2017 Apr 11;8(4):1076-1085. doi: 10.1016/j.stemcr.2016.12.017. Epub 2017 Jan 19.
Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs) from patients of different ethnicities, β-globin gene (HBB) haplotypes, and fetal hemoglobin (HbF) levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. Here, we describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. As a complement to this library, and as proof of principle for future cell- and gene-based therapies, we also designed and employed CRISPR/Cas gene editing tools to correct the sickle hemoglobin (HbS) mutation.
镰状细胞贫血影响着全球数百万人，是一个新兴的全球健康负担。作为 NIH 资助的下一代联盟的一部分，我们从不同种族、β-珠蛋白基因（HBB）单倍型和胎儿血红蛋白（HbF）水平的患者中生成了一个多样化、全面和完全特征化的镰状细胞疾病特异性诱导多能干细胞（iPSC）文库。iPSC 有望彻底改变我们研究人类发育、疾病建模的方式，也许最终还能治疗患者。在这里，我们描述了这个用于镰状细胞疾病研究的独特资源，包括影响疾病严重程度的新型单倍型特异性多态性，以及为这种表型多样化的疾病开发患者特异性治疗方法。作为该文库的补充，并且作为未来基于细胞和基因治疗的原理证明，我们还设计并使用了 CRISPR/Cas 基因编辑工具来纠正镰状血红蛋白（HbS）突变。
