Human placenta mesenchymal stem cells expressing exogenous kringle1-5 protein by fiber-modified adenovirus suppress angiogenesis.
Anti-angiogenesis gene therapy is considered a promising treatment for excessive vascularization. Mesenchymal stem cell (MSC)-based gene therapy may enhance the effect of anti-angiogenesis by maintaining a long therapeutic period in vivo. However, transduction efficiencies and transgene expression in MSC-based gene therapy should be improved. Here we report human placenta-derived MSC (HPMSC)-based gene therapy using a fiber-modified adenoviral vector carrying the kringle1-5 gene to maintain long-term survival and effectively suppress angiogenesis both in vitro and in vivo. HPMSCs infected by the adenoviral vector were transduced at high efficiency with a low multiplicity of infection, and the infected HPMSCs expressed exogenous kringle1-5 protein in vitro and in vivo. Infected HPMSCs were detected at 2 weeks in vivo by fluorescence imaging and immunohistochemistry of reporter gene expression. Importantly, the microvessel growth of aortic rings in vitro was inhibited by administration of infected HPMSCs expressing kringle1-5 protein (K1-5-HPMSCs) at day 6. In Matrigel plugs combined with K1-5-HPMSCs, microvessel density was decreased as detected by immunohistochemistry and blood flow was decreased as detected by the power Doppler contrast enhanced at day 14. The fiber-modified adenovirus is an effective gene vector for HPMSC-based gene therapy, which may be a promising strategy for cancer anti-angiogenesis.
Department of Ultrasound, First Affiliated Hospital of Harbin Medical University, Harbin, China.
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Y
Chu
Department of Gynecological Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
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H
Liu
Department of Gynecological Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
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G
Lou
Department of Ultrasound, First Affiliated Hospital of Harbin Medical University, Harbin, China.
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Zhang
Department of Ultrasound, First Affiliated Hospital of Harbin Medical University, Harbin, China.
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Wu
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D018082:Kringles; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D009389:Neovascularization, Pathologic; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy