造血干细胞（Hematopoietic stem cells）
基因治疗
最近几年，由于干细胞生物学、载体设计、细胞培养和基因转染系统研究不断深入，人们利用干细胞与基因治疗新技术，开展了某些严重遗传性疾病如 SCID，ADA-SCID和CGD等的临床试验，已经获得了初步成功106-108。然而，利用反转录载体进行基因治疗存在严重的安全性问题；这些载体 可以随机地整合某些活性基因附近或基因序列内，导致转染细胞过度扩增，某些X-SCID病人在基因治疗后出现了继发白血病109, 110。在临床前小鼠和猴实验中，也观察到类似的现象111,112。以HIV为骨架的慢病毒载体可以转染非增殖或缓慢增殖的细胞，因此，与反转录病毒比 较，慢病毒载体HSC转染效率较高113。转座子（transposon）是细胞基因组中移动的DNA成分，可以整合宿主DNA基因组中。转座子能转染人 CD34阳性细胞，包括NOD/SCID重建细胞，因此可作为一种基因治疗的非病毒载体系统114。与反转录载体不同，慢病毒载体和转座子整合基因或启动 子区域的倾向较低，导致插入畸变的危险性较小。
通过重新活化“干性”基因，可使体细胞，如皮肤成纤维细胞，重新编程为诱导多能干细胞（iPSC）。这种技术的建立，为纠正遗传性和获得性疾病的基因缺 陷，提供了疾病特异性治疗的新策略115。将正常的β-球蛋白基因转染自体的iPS细胞，可以修复小鼠镰刀细胞贫血模型的基因缺陷。基因修正的iPSC 细胞诱导分化为造血细胞，可成功植入受体小鼠，治疗镰刀细胞贫血116。此外，由Fanconi贫血和地中海贫血病人皮肤成纤维细胞编程构建的iPS细 胞，经基因修正后，可分化为红系和髓系祖细胞117, 118。目前，用于构建iPS细胞及基因修正的载体，大多数为反转录病毒和慢病毒载体。此外，有研究提示，利用反转录病毒载体转染iPS使之高表达 HOXB4，是iPS细胞分化的造血细胞具有可移植性的必要前提116。利用以上技术可以获得疾病特异性的iPS细胞和造血细胞，无论对研究和药物筛选， 都是非常有意义的119。然而，以iPS来源的造血细胞为基础的细胞与基因治疗，其临床应用的安全性和有效性，仍待基因组重新编程和基因纠正方案的进一步 成熟与完善，以避免基因组修饰出现持续而不可逆的改变120。此外，利用非基因操作手段诱导iPS细胞向HSC分化，使获得的造血细胞具有重建稳定持久的 多系造血能力，也是iPS细胞临床应用的必要基础。为促使该领域研究的进展，研制可靠的检定、分离和扩增造血细胞的试剂、培养方法和技术，是十分必要的。
注：加拿大StemCell公司和杭州百通生物技术有限公司联合推出造血干祖细胞分选和培养系列产品详情请向杭州百通生物技术有限公司垂询，或登陆网站http://www.stemcell.com或http://www.biowish.com。
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