Jo Jun-Ichiro, Nagaya Noritoshi, Miyahara Yoshinori, Kataoka Masaharu, Harada-Shiba Mariko, Kangawa Kenji, Tabata Yasuhiko
Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Tissue Eng. 2007 Feb;13(2):313-22. doi: 10.1089/ten.2006.0133.
It is expected that mesenchymal stem cells (MSCs) will be a cell source for cardiac reconstruction because of their differentiation potential and ability to supply growth factors. However, poor viability at the transplanted site often hinders the therapeutic potential of MSCs. Here, in a trial designed to address this problem, a non-viral carrier of cationized polysaccharide is introduced for genetic engineering of MSCs. Spermine-introduced dextran of cationized polysaccharide (spermine-dextran) was internalized into MSCs by way of a sugar-recognizable receptor to enhance the expression level of plasmid deoxyribonucleic acid (DNA). When genetically engineered by the spermine-dextran complex with plasmid DNA of adrenomedullin (AM), MSCs secreted a large amount of AM, an anti-apoptotic and angiogenic peptide. Transplantation of AM gene-engineered MSCs improved cardiac function after myocardial infarction significantly more than MSCs alone. Thus, this genetic engineering technology using the non-viral spermine-dextran is a promising strategy to improve MSC therapy for ischemic heart disease.
由于间充质干细胞（MSCs）具有分化潜能和提供生长因子的能力，有望成为心脏重建的细胞来源。然而，移植部位的低存活率常常阻碍了MSCs的治疗潜力。在此，在一项旨在解决这一问题的试验中，引入了一种阳离子化多糖的非病毒载体用于MSCs的基因工程。通过糖识别受体将引入精胺的阳离子化多糖葡聚糖（精胺-葡聚糖）内化到MSCs中，以提高质粒脱氧核糖核酸（DNA）的表达水平。当用精胺-葡聚糖复合物与肾上腺髓质素（AM）的质粒DNA对MSCs进行基因工程改造时，MSCs分泌大量的AM，一种抗凋亡和促血管生成的肽。与单独移植MSCs相比，移植AM基因工程化的MSCs能更显著地改善心肌梗死后的心脏功能。因此，这种使用非病毒精胺-葡聚糖的基因工程技术是改善缺血性心脏病MSCs治疗的一种有前景的策略。
