Homing of in vitro expanded Stro-1- or Stro-1+ human mesenchymal stem cells into the NOD/SCID mouse and their role in supporting human CD34 cell engraftment
Bensidhoum M, Chapel A, François S, Demarquay C, Mazurier C, Fouillard L, Bouchet S, Bertho JM, Gourmelon P, Aigueperse J, Charbord P, Gorin NC, Thierry D, Lopez M.
Blood - Volume 103, Issue 9, 1 May 2004, Pages 3313-3319
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 engraftment of human CD34+ cord blood cells in the nonobese diabetic/severe combined immunodeficiency (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 with 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 ß-globin with quantitative polymerase chain reaction [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 enhanced green fluorescent protein (eGFP) gene did not modify their cytokine release and their homing in NOD/ SCID mouse tissues. The difference between the hematopoietic 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. © 2004 by The American Society of Hematology.