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Marrow mesenchymal stem cells transduced with TPO/FL genes as support for ex vivo expansion of hematopoietic stem/progenitor cells
Authors:C.-g. Xie  J.-f. Wang  Y. Xiang  B.-b. Jia  L.-y. Qiu  L.-j. Wang  G.-z. Wang  G.-p. Huang
Affiliation:(1) Institute of Stem Cell Biology, College of Life Sciences, Zhejiang University, 232 Wen San Road, Hangzhou, 310012, P. R. China;(2) Institute of Life Science, Jiangsu University, Zhenjiang, 212013, P. R. China
Abstract:
A new marrow-derived mesenchymal stem cell (hMSC) line that could support expansion of hematopoietic stem/progenitor cells (HSPCs) was developed. Primary hMSCs were infected with retrovirus containing Flt-3 ligand and thrombopoietin genes. CD34+ cells from cord blood were expanded with primary hMSCs or transduced hMSCs. The expansion of total nucleated cells, CD34+ cells and mixed colonies containing erythroid and myeloid cells and megakaryocytes for 2 weeks coculture with transduced hMSCs was remarkably increased. The outputs of long-term culture-initiating cells for 2 and 4 weeks coculture with transduced hMSCs were also largely increased. The expansion rates of HSPCs with transduced hMSCs were unchanged for 6 weeks. In contrast, the expansion rates of HSPCs with primary hMSCs declined drastically through 6 weeks. SCID-repopulating cell expansion with transduced hMSCs for 4 weeks was significantly higher than that of uncultured CD34+ cells and HSPCs expanded with primary hMSCs. Received 21 June 2005; received after revision 30 July 2005; accepted 24 August 2005
Keywords:Mesenchymal stem cell  transduction  thrombopoietin  Flt-3 ligand  hematopoietic stem/progenitor cell  expansion
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