Abstract
Ex vivo expansion of primitive human haematopoietic stem cells (HSC) is clinically relevant for stem cell transplantation and gene therapy. Here, we demonstrate the selective expansion of CD34+CD38- cells from purified CD34+ cells upon stimulation with Flt3-ligand, stem cell factor and thrombopoietin. Over a 100-fold (range 80 to 128-fold) expansion of CD34+CD38- cells was observed with bone marrow and cord blood (CB). The expanded CD34+CD38- cells remained negative for lineage-specific markers and could be induced to differentiate into granulocytes, monocytes, megakaryocytes, erythrocytes, and T and B-lymphocytes in vitro. Lineage differentiation assays with single CD34+CD38- cells showed no loss of multilineage potential of expanded cells after ex vivo culture. We also demonstrated that the increase in frequency of CD34+CD38- cells was not as a result of the downregulation of CD38 expression during the culture. Quantitative analysis showed that the number of 6 week cobblestone area forming cells (CAFCwk6), a measure of proliferating HSC, in cytokine-stimulated CD34+ cells were increased by 20-fold. Expanded CD34+CD38- cells could be transduced efficiently with retroviruses encoding the low affinity nerve growth factor recepto...Continue Reading
References
Apr 1, 1992·Current Opinion in Immunology·G Keller
Jan 1, 1990·Annual Review of Immunology·K Dorshkind
Aug 1, 1990·Molecular and Cellular Biology·D G MillerA D Miller
Aug 1, 1995·International Immunology·F J StaalH Spits
Jan 1, 1994·Growth Factors·F M CicuttiniA W Boyd
May 1, 1993·The Journal of Experimental Medicine·W CraigP M Lansdorp
Oct 1, 1994·British Journal of Haematology·F BertoliniF Malavasi
Jun 1, 1996·The Journal of Experimental Medicine·A L PetzerC J Eaves
Jan 1, 1995·Annual Review of Cell and Developmental Biology·S J MorrisonI L Weissman
Dec 1, 1996·Nature Medicine·A LarochelleJ E Dick
Aug 18, 1997·The Journal of Experimental Medicine·M BhatiaJ E Dick
Oct 10, 1997·Human Gene Therapy·L RuggieriC Bordignon
Nov 14, 1997·Human Gene Therapy·B FehseM Stockschläder
Jan 1, 1997·Stem Cells·J E DickJ C Wang
Feb 12, 1998·European Journal of Radiology·C HoeffelJ C Hoeffel
Sep 12, 1998·Nature Medicine·M BhatiaJ E Dick
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·S S CaseG M Crooks
May 1, 1999·Human Gene Therapy·J DouglasJ V Garcia
May 26, 1999·Experimental Hematology·D S DonnellyD S Krause
Jun 23, 1999·Experimental Hematology·J C YoungB L Hill
Jun 23, 1999·Experimental Hematology·L J MurrayB L Hill
Jul 8, 1999·Human Gene Therapy·J T EvansJ V Garcia
May 16, 2000·Cancer Gene Therapy·Y Y NgF J Staal
Citations
Oct 21, 2006·Journal of Cancer Research and Clinical Oncology·Peter EbelingM Flasshove
Jan 23, 2003·Leukemia Research·Jane L Liesveld
May 25, 2005·Stem Cells and Development·Xianghui HeDavid T Harris
Apr 6, 2013·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Xin YuZong-jiang Gu
Apr 17, 2013·Cell Biology International·Xin YuHongwei Wang
Mar 30, 2006·Experimental Hematology·Kristin M HallEdward F Srour
May 20, 2016·Radiation Research·C VandevoordeH Thierens
Nov 27, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Francesca FicaraAlessandro Aiuti
Nov 25, 2003·Journal of Leukocyte Biology·Yuk Yin NgFrank J T Staal
Jul 16, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Maarten B RookmaakerVictor W M van Hinsbergh