Serial transplantations in nonobese diabetic/severe combined immunodeficiency mice of transduced human CD34+ cord blood cells:: Efficient oncoretroviral gene transfer and ex vivo expansion under serum-free conditions

被引:7
作者
Gammaitoni, Loretta
Lucchi, Simona
Bruno, Stefania
Tesio, Melania
Gunetti, Monica
Pignochino, Ymera
Migliardi, Giorgia
Lazzari, Lorenza
Aglietta, Massimo
Rebulla, Paolo
Piacibello, Wanda
机构
[1] Inst Canc Res & Treatment, Lab Med Oncol, Candiolo, Italy
[2] Osped Maggiore, Ctr Trasfus & Immunol Trapianti, Fdn Ist Ricovero & Cura Carattere Sci, Policlin Mangiagalli & Regina Elena, Milan, Italy
[3] Ist Auxol Italiano, Milan, Italy
关键词
cord blood; xenotransplantations; gene marking; oncoretroviral vectors; nonobese diabetic/severe combined immunodeficiency mice; hematopoietic stem cells; expansion; ex vivo gene transfer;
D O I
10.1634/stemcells.2005-0408
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Stable oncoretroviral gene transfer into hematopoietic stem cells (HSCs) provides permanent genetic disease correction. It is crucial to transplant enough transduced HSCs to compete with and replace the defective host hemopoiesis. To increase the number of transduced cells, the role of ex vivo expansion was investigated. For a possible clinical application, all experiments were carried out in serum-free media. A low-affinity nerve growth factor receptor (LNGFR) pseudotyped murine retroviral vector was used to transduce cord blood CD34(+) cells, which were then expanded ex vivo. These cells engrafted up to three generations of serially transplanted nonobese diabetic/severe combined immunodeficiency mice: 54.26% +/- 5.59%, 19.05% +/- 2.01%, and 6.15% +/- 5.16% CD45(+) cells from primary, secondary, and tertiary recipient bone marrow, respectively, were LNGFR(+). Repopulation in secondary and tertiary recipients indicates stability of transgene expression and long-term self-renewal potential of transduced HSCs, suggesting that retroviral gene transfer into HSCs, followed by ex vivo expansion, could facilitate long-term engraftment of genetically modified HSCs.
引用
收藏
页码:1201 / 1212
页数:12
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