Cotransplantation of cord blood hematopoietic stem cells and culture-expanded and GM-CSF-/SCF-transfected mesenchymal stem cells in SCID mice.
Mesenchymal stem cells (MSC) are multipotent in nature and believed to facilitate the engraftment of hematopoietic stem cells (HSC) when transplanted simultaneously in animal studies and even in human trials. In this study, we transfected culture-expanded MSC with granulocyte macrophage-colony stimulating factor (GMCSF) and stem cell factor (SCF) cytokine genes and then cotransplanted with mononuclear cells (MNC) to further promote HSC engraftment. MNC were harvested from cord blood and seeded in long-term culture for ex vivo MSC expansion. A total of 1 x 10(7) MNC plus MSC/microL were introduced to the tail vein of nonobese diabetic/severe combined immunodeficiency mice. After 6-8 weeks later, homing and engraftment of human cells were determined by flow cytometry and fluorescence in situ hybridization studies. The total nucleated cell count and the engraftment of CD45+/CD34+ cells and XX or XY positive human cells were significantly increased in cotransplanted mice and even higher with the cytokine gene-transfected MSC (GM-CSF>SCF, p<0.05) than in transplantation of MNC alone. These results suggest that MSC transfected with hematopoietic growth factor genes are capable of enhancing the hematopoietic engraftment. Delivering genes involved in homing and cell adhesions, CXCR4 or VLA, would further increase the efficiency of stem cell transplantation in the future.
Han
Jin-Yeong
JY
Department of Laboratory Medicine, Dong-A University College of Medicine, 1 3-ga, Dongdaesin-dong, Seo-gu, Busan, Korea. jyhan@dau.ac.kr
Goh
Rhee Young
RY
Seo
Su Yeong
SY
Hwang
Tae Ho
TH
Kwon
Hyuk Chan
HC
Kim
Sung Hyun
SH
Kim
Jae Seok
JS
Kim
Hyo Jin
HJ
Lee
Young Ho
YH
D000818:Animals; D024861:Genetic Enhancement / Q000379:methods; D006085:Graft Survival / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D011994:Recombinant Proteins; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods*
D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor