Cotransplantation of cord blood hematopoietic stem cells and culture-expanded and GM-CSF-/SCF-transfected mesenchymal stem cells in SCID mice.
Cotransplantation of cord blood hematopoietic stem cells and culture-expanded and GM-CSF-/SCF-transfected mesenchymal stem cells in SCID mice.
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DOI：
10.3346/jkms.2007.22.2.242
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发表时间：
2007-04
影响因子：
4.5
通讯作者：
Lee YH
中科院分区：
文献类型：
--
作者：
Han JY;Goh RY;Seo SY;Hwang TH;Kwon HC;Kim SH;Kim JS;Kim HJ;Lee YH
间充质干细胞(MSC)本质上是多能的，在动物实验中，甚至在人体试验中，当同时移植时，被认为有助于造血干细胞(HSC)的植入。本研究将粒细胞巨噬细胞集落刺激因子(GM-CSF)和干细胞因子(SCF)细胞因子基因导入体外扩增的MSC，并与单个核细胞(MNC)共移植，以进一步促进HSC的植入。从脐带血中获取MNC，在长期培养条件下进行MSC体外扩增。非肥胖型糖尿病/重度联合免疫缺陷小鼠尾静脉注射1×107单核细胞+骨髓间充质干细胞/微球L。6~8周后，用流式细胞仪和荧光原位杂交技术检测细胞的归巢和植入情况。联合移植组小鼠有核细胞总数、CD45+/CD34+细胞和XX、XY阳性细胞数均显著增加，且联合应用细胞因子基因修饰的MSC(GM-CSF和GT；SCF，p<；0.05)的移植效果明显高于单纯MNC移植。这些结果提示，骨髓间充质干细胞转导了造血生长因子基因，能够增强骨髓间充质干细胞的植入。携带与归巢和细胞黏附有关的基因，CXCR4或VLA，将进一步提高未来干细胞移植的效率。
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 (GM-CSF) 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 1×107 MNC plus MSC/µL 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.
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影响因子：
6.5
作者：
Erices, A;Conget, P;Minguell, JJ
通讯作者：
Minguell, JJ
影响因子：
--
作者：
Jones, EA;Kinsey, SE;McGonagle, D
通讯作者：
McGonagle, D
影响因子：
2.6
作者：
Wagner, W;Wein, F;Ho, AD
通讯作者：
Ho, AD
影响因子：
4.8
作者：
Maitra, B;Szekely, E;Koç, O
通讯作者：
Koç, O
DOI：
10.1089/152581600750062264
发表时间：
2000-12-01
期刊：
JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH
影响因子：
--
作者：
Majumdar, MK;Thiede, MA;Gerson, SL
通讯作者：
Gerson, SL