Cell Transplantation | |
Introduction of hIGF-1 Gene into Bone Marrow Stromal Cells and Its Effects on the Cell's Biological Behaviors | |
Article | |
Yan Wu1  Chengjun Hu1  Qiao Wang1  Jian Song2  Yu Wan3  | |
[1] Department of Anatomy and Embryology, Wuhan University School of Medicine, Wuhan, P.R. China;Department of Anatomy and Embryology, Wuhan University School of Medicine, Wuhan, P.R. China; Key Laboratory of Allergy and Immune-Related Diseases, and Center for Medical Research, Wuhan University, Wuhan, P.R. China;Key Laboratory of Allergy and Immune-Related Diseases, and Center for Medical Research, Wuhan University, Wuhan, P.R. China; | |
关键词: Bone marrow stromal cell; hIGF-1; Proliferation; Self-renewal; Multipotency; | |
DOI : 10.3727/096368908786991506 | |
received in 2007-10-27, accepted in 2008-04-14, 发布年份 2008 | |
来源: Sage Journals | |
【 摘 要 】
Autologous and gene-modified bone marrow stromal cells (MSCs) have shown a bright future in clinical applications. However, does a gene-modified MSC still maintain its stem cell-like properties? To answer this question, human IGF-1 was introduced into rat MSCs using a recombinant retroviral vector and the effects of the gene manipulation on the cells' behaviors were investigated. The MSCs transfected with hIGF-1 could secrete 6.7-fold higher IGF-1 than the native cells. These MSCs had an elevated baseline activity of ERK signaling, an enhanced proliferation, increased accumulative numbers of cell doublings, and a reduced apoptosis; they showed upregulated expressions of OCT-4, CYP51, and SM22α, and a downregulated expression of nestin. This indicates that the overexpressed IGF-1 enhances the MSCs' self-renewal, endodermal and mesodermal differentiation, but weakens their neuronal potential. Although a puromycin selection after hIGF-1 gene transfection could produce a purer transfected MSC population with stronger ability to express functional hIGF-1, it induced premature senescence of the selected cells by activating oncogene Ras, leading to a shortened replicative life span and a weakened multipotency.
【 授权许可】
Unknown
© 2008 Cognizant Comm. Corp.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO202212206539151ZK.pdf | 1077KB | download |
【 参考文献 】
- [1]
- [2]
- [3]
- [4]
- [5]
- [6]
- [7]
- [8]
- [9]
- [10]
- [11]
- [12]
- [13]
- [14]
- [15]
- [16]
- [17]
- [18]
- [19]
- [20]
- [21]
- [22]
- [23]
- [24]
- [25]
- [26]
- [27]
- [28]
- [29]
- [30]
- [31]
- [32]
- [33]
- [34]
- [35]
- [36]
- [37]
- [38]