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.
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 beta-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.
Bensidhoum
Morad
M
Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle, Faculté de Médecine Saint Antoine et IRSN, EA 1638 et Inserm U76, Paris, France.
Chapel
Alain
A
Francois
Sabine
S
Demarquay
Christelle
C
Mazurier
Christelle
C
Fouillard
Loic
L
Bouchet
Sandrine
S
Bertho
Jean Marc
JM
Gourmelon
Patrick
P
Aigueperse
Jocelyne
J
Charbord
Pierre
P
Gorin
Norbert Claude
NC
Thierry
Dominique
D
Lopez
Manuel
M
D000818:Animals; D001854:Bone Marrow Cells; D002465:Cell Movement; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D006085:Graft Survival; D006410:Hematopoiesis; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D023421:Models, Animal; D009687:Nuclear Proteins; D009928:Organ Specificity; D013154:Spleen / Q000166:cytology; D014183:Transplantation, Heterologous
D009687:Nuclear Proteins; C108522:STAG1 protein, human