Ex vivo expansion of haematopoietic stem cells and gene therapy development

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.