Cytokine-pretreatment of CD34(+) cord blood stem cells in vitro reduces long-term cell engraftment in NOD/SCID mice.
Stem cell homing, engraftment and organ regeneration are controlled by cytokines, chemokines and cell-cell interactions. In this paper, cytokine effects on homing- and engraftment-related characteristics of CD34(+) cord blood cells were examined. Untreated CD34(+) cells were mainly in the G(0)/G(1) cell cycle phase, expressed adhesion receptors on a low level, were positive for vimentin, and negative for the epithelial marker cytokeratin 8/18. Treatment with stem cell factor (SCF) stimulated cell proliferation, increased the number of cells in S and G(2)/M cell cycle phase as well as the expression of adhesion receptors. The expression of cytokeratin 8/18 was increased and that of vimentin remained unchanged. Hepatocyte growth factor (HGF) did not stimulate cell proliferation and expression of adhesion receptors, but increased expression of cytokeratin 8/18. In NOD/SCID mice, kinetics of stem cell distribution revealed a fast elimination of human cells from blood. An increase in the number of engrafted cells was observed in different mouse organs in a time-dependent manner, preferentially in bone marrow, spleen and liver. Pretreatment with SCF resulted in reduction of long-term engraftment in bone marrow. HGF pretreatment of cord blood cells showed no significant effects on long-term engraftment capacity in mouse organs compared to untreated cells. Our data provide in vivo evidence that pretreatment of CD34(+) cells with SCF reduces long-term cell engraftment in NOD/SCID mice.
Wulf-Goldenberg
Annika
A
Max-Delbrück-Center for Molecular Medicine, Berlin-Buch, Germany.
Eckert
Klaus
K
Fichtner
Iduna
I
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation; D005312:Fetal Blood / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D007633:Keratins / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D019089:Stem Cell Factor / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D014746:Vimentin / Q000378:metabolism
D015703:Antigens, CD; D018952:Antigens, CD34; D019089:Stem Cell Factor; D014746:Vimentin; D017228:Hepatocyte Growth Factor; D007633:Keratins