Current status of stem cell therapy and prospects for gene therapy for the disorders of globin synthesis
Current status of stem cell therapy and prospects for gene therapy for the disorders of globin synthesis
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DOI：
10.1016/s0950-3536(98)80078-4
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发表时间：
1998-03-01
期刊：
影响因子：
--
通讯作者：
Blau, CA
中科院分区：
文献类型：
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作者：
Blau, CA
镰状细胞贫血症和β地中海贫血症如今可以通过干细胞移植治愈。然而，干细胞移植固有的缺点强调了对更好疗法的需求。最近一项具有潜在重大意义的发现是，完全根除宿主造血并不是地中海贫血和镰状细胞贫血取得治疗效果的绝对要求。未来的干细胞移植方案将使用毒性较小的预处理方案，以努力实现供体和宿主造血成分之间稳定的混合嵌合状态。对珠蛋白基因调控和干细胞生物学的进一步了解将使镰状细胞贫血症和β地中海贫血症的第一次基因治疗试验在相对不久的将来成为可能。最初的基因治疗方案将强调安全性，可能靶向祖细胞，并将涉及反复循环的动员，转导和再输注，很少或没有条件。这些第一代基因治疗试验不太可能带来重大的治疗益处，但将为后续更有效的方案提供基础。
Sickle cell anaemia and beta-thalassaemia are today curable through the use of stem cell transplantation. Nevertheless, the disadvantages inherent in stem cell transplantation underscore the need for better therapies. A recent finding of potentially major importance is that complete eradication of host haematopoiesis is not an absolute requirement for achieving therapeutic effects in thalassaemia and sickle cell anaemia. Future stem cell transplantation protocols will use less toxic conditioning regimens in an effort to achieve a state of stable mixed chimerism between donor and host haematopoietic elements. An improved understanding of globin gene regulation and stem cell biology will allow for the first gene therapy trials for sickle cell anaemia and beta-thalassaemia in the relatively near future. Initial gene therapy protocols will emphasize safety, are likely to target progenitor cells, and will involve repeated cycles of mobilization, transduction and reinfusion, with little or no conditioning. These first generation gene therapy trials are unlikely to confer major therapeutic benefits, but will provide the foundation upon which subsequent, more effective protocols will be based.