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Ex vivo expansion of umbilical cord blood (UCB) CD34 + cells alters the expression and function of α4β1 and α5β1 integrins
Author(s) -
Ramírez Manuel,
Segovia José Carlos,
Benet Isana,
Arbona Cristina,
Güenechea Guillermo,
Blaya Carolina,
GarcíaConde Javier,
Bueren Juan A.,
Prosper Felipe
Publication year - 2001
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2001.03084.x
Subject(s) - haematopoiesis , progenitor cell , homing (biology) , ex vivo , transplantation , cord blood , stem cell , cd34 , biology , immunology , integrin , cell adhesion molecule , microbiology and biotechnology , in vivo , medicine , cell , ecology , genetics
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 α4, α5, β1, αΜM and β2 integrins. However, a significant decrease in the adhesion of progenitor cells 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 β1 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 completely abrogated 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 β1 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.