Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA, Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA; Division of Pediatric Hematology/Oncology, Children's Hospital Boston, Boston, Massachusetts 02115, USA.
Cold Spring Harb Perspect Med. 2012 Apr;2(4):a011841. doi: 10.1101/cshperspect.a011841.
Pluripotent stem cells (PSCs) hold great promise for research and treatment of hemoglobinopathies. In principle, patient-specific induced pluripotent stem cells could be derived from a blood sample, genetically corrected to repair the disease-causing mutation, differentiated into hematopoietic stem cells (HSCs), and returned to the patient to provide a cure through autologous gene and cell therapy. However, there are many challenges at each step of this complex treatment paradigm. Gene repair is currently inefficient in stem cells, but use of zinc finger nucleases and transcription activator-like effector nucleases appear to be a major advance. To date, no successful protocol exists for differentiating PSCs into definitive HSCs. PSCs can be directly differentiated into primitive red blood cells, but not yet in sufficient numbers to enable treating patients, and the cost of clinical scale differentiation is prohibitively expensive with current differentiation methods and efficiencies. Here we review the progress, promise, and remaining hurdles in realizing the potential of PSCs for cell therapy.
多能干细胞（PSCs）在研究和治疗血红蛋白病方面具有巨大的潜力。原则上，可以从血液样本中获得患者特异性诱导多能干细胞，对其进行基因修正以修复致病突变，分化为造血干细胞（HSCs），并将其归还给患者，通过自体基因和细胞治疗实现治愈。然而，在这个复杂的治疗范例的每一步都存在许多挑战。目前，干细胞中的基因修复效率不高，但锌指核酸酶和转录激活因子样效应物核酸酶的使用似乎是一个重大进展。迄今为止，尚无将 PSCs 分化为明确的 HSCs 的成功方案。PSCs 可以直接分化为原始红细胞，但数量还不足以治疗患者，并且目前的分化方法和效率使得临床规模的分化成本过高。在这里，我们回顾了实现 PSCs 细胞治疗潜力的进展、承诺和仍然存在的障碍。
