Evaluation of a novel poly(amidoamine) with pendant aminobutyl group on the cellular properties of transfected bone marrow mesenchymal stem cells
Evaluation of a novel poly(amidoamine) with pendant aminobutyl group on the cellular properties of transfected bone marrow mesenchymal stem cells
复制标题
具有氨基丁基侧基的新型聚酰胺基胺对转染骨髓间充质干细胞细胞特性的评价
DOI：
10.1002/jbm.a.36264
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发表时间：
2018-03-01
影响因子：
4.9
通讯作者：
Peng, Lin
中科院分区：
文献类型：
--
作者：
Chen, Lili;Long, Dan;Peng, Lin
基于干细胞的基因治疗已被认为是许多退行性疾病的治疗。基因修饰的干细胞应保持其生殖活性而不丧失干细胞特性，包括遗传表型和分化潜能。本研究采用本课题组设计的新型氨基丁基侧链聚酰胺胺（PAA-BA）转染骨髓间充质干细胞（BMSCs），观察转染后BMSCs的DNA含量、集落形成能力、遗传表型和多向分化能力。还使用了两种经典的非病毒基因递送载体，聚乙烯亚胺（PEI）和Lipofectamine 2000（LP 2000）。与未转染组相比，PAA-BA显示出轻微的DNA含量降低，但保持了BMSCs的表型、繁殖活性和多向分化潜能（成骨、软骨、脂肪和神经分化）。PAA-BA和PEI转染的BMSCs在体外均表现出较好的成骨分化能力，但成脂分化和成熟神经分化受到抑制。转染LP 2000和PEI的BMSCs的DNA含量和增殖活性均显著降低。结果表明，PAA-BA是一种安全的基因转染载体，在骨髓间充质干细胞的成骨分化和神经分化中发挥作用。本研究为PAA-BA在骨髓基质细胞基因治疗中的应用提供了新的思路，尤其是在骨和神经相关疾病的基因治疗中。(c)2017 Wiley Periodicals，Inc. J Biomed Mater Res Part A：106A：686-697，2018.
Stem cell-based gene therapy has been considered in the treatment of many degenerative diseases. Gene-modified stem cells should maintain its reproductive activity without losing stem cell properties, including genetic phenotype and differentiation potential. In the study, a novel poly (amidoamine) with pendant aminobutyl group (PAA-BA) designed by our group was used in the transfection of bone marrow mesenchymal stromal cells (BMSCs) and the cellular properties post-transfection were evaluated, including DNA content, colony forming capacity, genetic phenotype, and multi-directional differentiation. Two classical non-viral gene delivery vectors, polyethylenimine (PEI) and Lipofectamine 2000 (LP2000) were also used. Compared to non-transfected group, PAA-BA showed minor decreased DNA content but maintained BMSCs' phenotype, reproductive activity and multi-differentiation potential (osteogenic, chondrogenic, adipogenic, and neurogenic differentiation). Both PAA-BA and PEI transfected BMSCs demonstrated improved osteogenic differentiation ability at late stage but suppressed adipogenic as well as mature neural differentiation in vitro. LP2000 and PEI transfected BMSCs displayed significantly lower DNA content and reproductive activity. These findings suggest that PAA-BA is one of safe gene delivery vectors in BMSCs transfection and plays a role in stem cell's osteogenic and neurogenic differentiation. This study proposes the potential application of PAA-BA in BMSCs based gene therapy, in particular bone and nerve relative diseases. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 686-697, 2018.