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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3313-3319.
Prepublished online as a Blood First Edition Paper on January 8, 2004; DOI 10.1182/blood-2003-04-1121.
Submitted April 18, 2003
Accepted December 6, 2003
Homing of in vitro expanded Stro-1- or Stro-1+ human mesenchymal stem cells into the nod/scid mouse. Their role in supporting human CD34 cell engraftment
Morad BENSIDHOUM, Alain CHAPEL, Sabine FRANCOIS, Christelle DEMARQUAY, Christelle MAZURIER, Loic FOUILLARD, Sandrine BOUCHET, Jean Marc BERTHO, Patrick GOURMELON, Jocelyne AIGUEPERSE, Pierre CHARBORD, Norbert Claude GORIN, Dominique THIERRY, and Manuel LOPEZ*
Hematologie, Laboratoire de Therapie Cellulaire et de Radioprotection Accidentelle, Faculte de Medecine Saint Antoine et IRSN, EA 1638 et INSERM U76, Paris, France; Institut de Radioprotection et de Surete Nucleaire, Fontenay Aux Roses, France
Institut de Radioprotection et de Surete Nucleaire, Fontenay Aux Roses, France
Hematologie, Laboratoire de Therapie Cellulaire et de Radioprotection Accidentelle, Faculte de Medecine Saint Antoine et IRSN, EA 1638 et INSERM U76, Paris, France
Laboratoire d'Hematopoiese, Faculte de Medecine, Tours, France
* Corresponding author; email: manuel.lopez{at}chusa.jussieu.fr.
The Stro-1 antigen potentially defines a mesenchymal stem cell (MSC) progenitor subset. We here report on the role of human ex vivo expanded selected-Stro-1+ or -Stro-1- MSC subsets on the engrafment of human CD34+ cord blood cells in the NOD/SCID mouse model. The data show that cotransplantation of expanded Stro-1- cells with CD34+ cells resulted in a significant increase of human CD45, CD34, CD19 and CD11b cells detected in blood or in bone marrow (BM) and spleen as compared to the infusion of CD34+ cells alone. Infusion into mice of expanded Stro-1+ and Stro-1- cells (without CD34+ cells) showed that the numbers of Stro-1+-derived (as assessed by DNA analysis of human  GLOBIN with quantitative PCR) were higher than Stro-1--derived cells in spleen, muscles, BM and kidneys, while more Stro-1--derived than Stro-1+-derived cells were found in lungs. The transduction of expanded Stro-1+ cells with an eGFP gene did not modify their cytokine release and their homing in NOD/SCID mouse tissues. The difference between the hemopoeitic support and the homing capabilities of expanded Stro-1+ and Stro-1- cells may be of importance for clinical therapeutic applications: Stro-1+ cells may rather be used for gene delivery in tissues while Stro-1- cells may rather be used to support hematopoietic engraftment.
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