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TRANSLATIONAL AND CLINICAL RESEARCH |
aLaboratoire dHématologie, Unité de Formation et de Recherche EA1638, Université Pierre et Marie Curie, CHU Saint Antoine, Paris, France;
bUMR 7151 CNRS - Université Paris 7 and Laboratoire dImmunologie Cellulaire et Immunopathologie de lEcole Pratique des Hautes Etudes, Institut Universitaire dHématologie, Hôpital Saint-Louis, Paris, France;
cService dHématologie Biologique, Hôpital Armand Trousseau, Assistance Publique Hôpitaux de Paris, France;
dUMR 7087 CNRS - Université Pierre et Marie Curie, Hôpital de la Pitié-Salpêtrière, Paris, France
Key Words. Ex vivo expansion • Cord blood • Hematopoietic progenitor cells • Lymphopoiesis • T-cell repertoire • Dendritic cell differentiation • Immune competence
Correspondence: Luc Douay, M.D., Ph.D., Service dHématologie Biologique, Hôpital Armand Trousseau, 26 avenue du Docteur Arnold Netter, 75012 Paris, France. Telephone: +33-1-44-73-62-22; Fax: +33-1-44-73-63-33; e-mail: luc.douay{at}trs.aphp.fr
Received February 21, 2006;
accepted for publication May 23, 2006.
We examined whether ex vivo expansion of umbilical cord blood progenitor cells affected their capacity to generate immune cells such as T lymphocytes (TLs) and dendritic cells (DCs). The capacity to generate TLs from cord blood CD34+ cells expanded for 14 days (d14) was compared with that of nonexpanded CD34+ cells (d0) using fetal thymus organ cultures or transfer into nonobese diabetic/severe combined immunodeficient mice. The cell preparations yielded comparable percentages of immature (CD4+CD8, CD4+CD8+) TLs and functional mature (CD3+CD4+, CD3+CD8+) TLs with an analogous TCR (T-cell receptor)-Vß repertoire pattern. As regards DCs, d0 and d14 CD34+ cells also yielded similar percentages of CD1a+ DCs with the same expression levels of HLA-DR, costimulatory and adhesion molecules, and chemokine receptors. DCs derived from either d14 or d0 CD34+ stimulated allogeneic TLs to the same extent, and the cytokine pattern production of these allogeneic TLs was similar with no shift toward a predominant Th1 or Th2 response. Even though the intrinsic capacity of d14 CD34+ cells to generate DCs was 13-fold lower than that of d0 CD34+ cells, this reduction was offset by the prior amplification of the CD34+ cells, resulting in the overall production of 15-fold more DCs. These data indicate that ex vivo expansion of CD34+ cells does not impair T lymphopoiesis nor DC differentiation capacity.
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