Introduction of hIGF-1 Gene into Bone Marrow Stromal Cells and Its Effects on the Cell's Biological Behaviors

Cell Transplantation

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.