Optimized lentiviral transduction of human amniotic mesenchymal stromal cells

被引:4
|
作者
Pisano, Federica [1 ,2 ,3 ]
Mura, Manuela [1 ,2 ]
Ciuffreda, Maria Chiara [1 ,2 ]
Calabro, Federica [1 ,2 ]
Lanzo, Nicola [3 ]
Gnecchi, Massimiliano [1 ,2 ,3 ,4 ]
机构
[1] Fdn IRCCS Policlin San Matteo, Dept Internal Med & Infect Dis, Coronary Care Unit, Pavia, Italy
[2] Fdn IRCCS Policlin San Matteo, Lab Expt Cardiol Cell & Mol Therapy, Pavia, Italy
[3] Univ Pavia, Unit Cardiol, Dept Mol Med, Pavia, Italy
[4] Univ Cape Town, Dept Med, Rondebosch, South Africa
关键词
Lentivirus; Mesenchymal stromal cells; Gene therapy; Stem cell therapy; Heart disease; HEPATOCYTE GROWTH-FACTOR; MARROW STEM-CELLS; BONE-MARROW; CARDIAC-FUNCTION; DIFFERENTIATION; PROTECTION; DELIVERY; THERAPY; CARDIOMYOCYTES; MYOCARDIUM;
D O I
10.1016/j.phrs.2017.11.014
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Mesenchymal stromal cells are excellent candidates for regenerative medicine since they are multipotent, easy to isolate, can be expanded to obtain clinically relevant numbers and are immunoprivileged. Stable genetic modification with viral vectors can improve mesenchymal stromal cell function and enhance their therapeutic potential. However, standard viral vectors achieve sub-optimal transduction efficiency with a single infection. On the other hand, multiple transduction cycles or antibiotic-based selection methods may alter the stem cell phenotype. We hypothesized that the use of lentiviral vectors containing specific regulatory sequences may result in improved transduction efficiency. Thus, we compared two types of third generation lentiviral vectors, one of which, the pLenti7.3 vector, contains the optimized sequences for Polypurine Tract and Woodchuck Post-transcriptional Regulatory Element. We demonstrated that with the pLenti7.3 it is possible to efficiently transduce human mesenchymal stromal cells with a single transduction cycle. Additionally, we successfully showed that by using the pLenti7.3 vector it is possible to efficiently over-express different growth factors, particularly relevant for cardiac protection and differentiation, in human mesenchymal stromal cells. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:49 / 57
页数:9
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