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Titolo:
Ex vivo expansion of umbilical cord blood (UCB) CD34(+) cells alters the expression and function of alpha 4 beta 1 and alpha 5 beta 1 integrins
Autore:
Ramirez, M; Segovia, JC; Benet, I; Arbona, C; Guenechea, G; Blaya, C; Garcia-Conde, J; Bueren, JA; Prosper, F;
Indirizzi:
Univ Valencia, Hosp Clin Univ, Dept Hematol & Oncol Med, Valencia, Spain Univ Valencia Valencia Spain Dept Hematol & Oncol Med, Valencia, Spain CIEMAT, Unidad Biol Mol & Celular & Terapia Genica, E-28040 Madrid, Spain CIEMAT Madrid Spain E-28040 ular & Terapia Genica, E-28040 Madrid, Spain
Titolo Testata:
BRITISH JOURNAL OF HAEMATOLOGY
fascicolo: 1, volume: 115, anno: 2001,
pagine: 213 - 221
SICI:
0007-1048(200110)115:1<213:EVEOUC>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEMATOPOIETIC STEM-CELLS; CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW; PERIPHERAL-BLOOD; PROGENITOR CELLS; ACTIVATED ALPHA-4-BETA-1; REPOPULATING CELLS; SELF-RENEWAL; CYCLE STATUS; ADHESION;
Keywords:
homing; umbilical cord blood; ex vivo expansion; integrins; NOD/SCID;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Prosper, F Univ Navarra Clin, Dept Haematol & Cell Therapy, Pamplona 31080, Spain Univ Navarra Clin Pamplona Spain 31080 Pamplona 31080, Spain
Citazione:
M. Ramirez et al., "Ex vivo expansion of umbilical cord blood (UCB) CD34(+) cells alters the expression and function of alpha 4 beta 1 and alpha 5 beta 1 integrins", BR J HAEM, 115(1), 2001, pp. 213-221

Abstract

We have investigated the influence of ex vivo expansion of human CD34(+) cord blood cells on the expression and function of adhesion molecules involved in the homing and engraftment of haematopoietic progenitors. Ex vivo expansion of umbilical cord blood CD34(+) cells for 6 d in the presence of interleukin 3 (IL-3), IL-6 and stem cell factor (SCF) or IL-11, SCF and Flt-3L, resulted in increased expression of alpha4, alpha5, beta1, alphaM and beta2 integrins. However, a significant decrease in the adhesion of progenitorcells to fibronectin was observed after the ex vivo culture (adhesion of granulocyte-macrophage colony-forming units (CFU-GM) was 22 +/- 4% in fresh cells versus 5 +/- 2% and 2 +/- 2% in each combination of cytokines). Incubation with the PI integrin-activating antibody TS2/16 restored adhesion to fibronectin. Transplantation of ex vivo expanded umbilical cord blood CD34() cells was associated with an early delayed engraftment in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Incubation of cells with the monoclonal antibody TS2/16 before transplantation almost completelyabrogated NOD/SCID repopulating ability of both fresh and expanded CD34(+)cells. The seeding efficiency of fresh and expanded CD34(+) cells was similar, but markedly reduced after incubation with the TS2/16 monoclonal antibody. Our results show that functional activation of beta1 integrins could overcome the decreased very late antigen (VLA)-4- and VLA-5-mediated adhesion observed after ex vivo expansion of haematopoietic progenitors. However, in vivo, these effects induced an almost complete abrogation of the homing and repopulating ability of CD34(+) UCB cells.

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Documento generato il 02/04/20 alle ore 02:40:28