CXCR4-transgene expression significantly improves marrow engraftment of cultured hematopoietic stem cells

被引：98

作者：

Brenner, S

Whiting-Theobald, N

Kawai, T

Linton, GF

Rudikoff, AG

Choi, U

Ryser, MF

Murphy, PM

Sechler, JMG

Malech, HL

机构：

[1] Univ Clin Carl Gustav Carus, Dept Pediat, D-01307 Dresden, Germany

[2] NIAID, Host Def Lab, NIH, Bethesda, MD USA

[3] Jikei Univ, Sch Med, Dept Pediat, Tokyo, Japan

来源：

STEM CELLS | 2004年 / 22卷 / 07期

关键词：

engraftment; CXCR4; ex vivo gene transfer; hematopoietic stem cells (HSCs);

D O I：

10.1634/stemcells.2003-0196

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Hematopoietic stem cells (HSCs) lose marrow reconstitution potential during ex vivo culture. HSC migration to stromal cell-derived factor (SDF)-1 (CXCL12) correlates with CXC chemokine receptor 4 (CXCR4) expression and marrow engraftment. We demonstrate that mobilized human CD34(+) peripheral blood stem cells (CD34(+) PBSCs) lose CXCR4 expression during prolonged culture. We transduced CD34(+) PBSCs with retrovirus vector encoding human CXCR4 and achieved 18-fold more CXCR4 expression in over 87% of CD34(+) cells. CXCR4-transduced cells yielded increased calcium flux and up to a 10-fold increase in migration to SDF-1. Six-day cultured CXCR4-transduced cells demonstrated significant engraftment in nonobese diabetic/severe combined immunodeficient mice under conditions in which control transduced cells resulted in low or no engraftment. We conclude that transduction-mediated overexpression of CXCR4 significantly improves marrow engraftment of cultured PBSCs.

引用

收藏

页码：1128 / 1133

页数：6

相关论文

共 13 条

[1] Mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure [J].

Abkowitz, JL ;

Robinson, AE ;

Kale, S ;

Long, MW ;

Chen, J .

BLOOD, 2003, 102 (04) :1249-1253

[2] Concentrated RD114-pseudotyped MFGS-gp91phox vector achieves high levels of functional correction of the chronic granulomatous disease oxidase defect in NOD/SCID/β2-microglobulin-/- repopulating mobilized human peripheral blood CD34+ cells [J].

Brenner, S ;

Whiting-Theobald, NL ;

Linton, GF ;

Holmes, KL ;

Anderson-Cohen, M ;

Kelly, PF ;

Vanin, EF ;

Pilon, AM ;

Bodine, DM ;

Horwitz, ME ;

Malech, HL .

BLOOD, 2003, 102 (08) :2789-2797

[3] Transgenic expression of stromal cell-derived factor-1/CXC chemokine ligand 12 enhances myeloid progenitor cell survival/antiapoptosis in vitro in response to growth factor withdrawal and enhances myelopoiesis in vivo [J].

Broxmeyer, HE ;

Cooper, S ;

Kohli, L ;

Hangoc, G ;

Lee, Y ;

Mantel, C ;

Clapp, DW ;

Kim, CH .

JOURNAL OF IMMUNOLOGY, 2003, 170 (01) :421-429

[4] Cytokine expansion culture of cord blood CD34+ cells induces marked and sustained changes in adhesion receptor and CXCR4 expressions [J].

Denning-Kendall, P ;

Singha, S ;

Bradley, B ;

Hows, J .

STEM CELLS, 2003, 21 (01) :61-70

[5] Ex vivo treatment of proliferating human cord blood stem cells with stroma-derived factor-1 enhances their ability to engraft NOD/SCID mice [J].

Glimm, H ;

Tang, P ;

Clark-Lewis, I ;

von Kalle, C ;

Eaves, C .

BLOOD, 2002, 99 (09) :3454-3457

[6] Overexpression of CXCR4 on human CD34+ progenitors increases their proliferation, migration, and NOD/SCID repopulation [J].

Kahn, J ;

Byk, T ;

Jansson-Sjostrand, L ;

Petit, I ;

Shivtiel, S ;

Nagler, A ;

Hardan, I ;

Deutsch, V ;

Gazit, Z ;

Gazit, D ;

Karlsson, S ;

Lapidot, T .

BLOOD, 2004, 103 (08) :2942-2949

[7] Chemokine SDF-1 enhances circulating CD34+ cell proliferation in synergy with cytokines:: possible role in progenitor survival [J].

Lataillade, JJ ;

Clay, D ;

Dupuy, C ;

Rigal, S ;

Jasmin, C ;

Bourin, P ;

Le Bousse-Kerdilès, MC .

BLOOD, 2000, 95 (03) :756-768

[8] Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide [J].

Lévesque, JP ;

Hendy, J ;

Takamatsu, Y ;

Simmons, PJ ;

Bendall, LJ .

JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (02) :187-196

[9] Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist [J].

Liles, WC ;

Broxmeyer, HE ;

Rodger, E ;

Wood, B ;

Hübel, K ;

Cooper, S ;

Hangoc, G ;

Bridger, GJ ;

Henson, GW ;

Calandra, G ;

Dale, DC .

BLOOD, 2003, 102 (08) :2728-2730

[10] The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34+ cells:: role in transendothelial/stromal migration and engraftment of NOD/SCID mice [J].

Peled, A ;

Kollet, O ;

Ponomaryov, T ;

Petit, I ;

Franitza, S ;

Grabovsky, V ;

Slav, MM ;

Nagler, A ;

Lider, O ;

Alon, R ;

Zipori, D ;

Lapidot, T .

BLOOD, 2000, 95 (11) :3289-3296