Zubler Rudolf H
Division of Hematology, Department of Internal Medicine, Hôpitaux Universitaires de Genève, Genève, Switzerland.
Swiss Med Wkly. 2006 Dec 23;136(49-50):795-9. doi: 10.4414/smw.2006.11424.
The results of a research project on ex vivo expansion of human haematopoietic stem cells (HSC) and development of gene therapy, funded by the Swiss National Research Program 46, are summarised and discussed in the context of current progresses and difficulties in these fields. A routine method for ex vivo expansion of human HSC is not yet available. However, stem cell biology has progressed importantly in recent years; ex vivo expansion of human HSC should become possible in the near future. Regarding gene therapy development, we obtained with HIV-1-derived bicistronic lentiviral vectors efficient delivery of genes into immature haematopoietic cells and also primary human B lymphocytes. However, clinical gene therapy still faces a variety of problems. For the (into chromosomes) integrating lentivectors, currently the most promising tools for HSC-based gene therapy, the risks of insertional mutagenesis need to be fully assessed before larger clinical trials can start.
由瑞士国家研究计划46资助的一项关于人类造血干细胞（HSC）体外扩增及基因治疗发展的研究项目结果，在这些领域当前的进展和困难背景下进行了总结和讨论。目前尚无用于人类HSC体外扩增的常规方法。然而，近年来干细胞生物学取得了重要进展；人类HSC的体外扩增在不久的将来应该成为可能。关于基因治疗的发展，我们使用源自HIV-1的双顺反子慢病毒载体实现了将基因有效递送至未成熟造血细胞以及原代人类B淋巴细胞。然而，临床基因治疗仍面临各种问题。对于（整合到染色体中）的整合慢病毒载体，目前是基于HSC的基因治疗最有前景的工具，在能够开展更大规模的临床试验之前，插入诱变的风险需要得到充分评估。
