据物理学家组织网4月2日（北京时间）报道，美国维克森林浸礼会医学中心再生医学研究所科学家通过基因工程修改了一种干细胞，使其表达一种常见疱疹病毒的蛋白质，从而能躲避免疫系统攻击，大大提高了存活率。受伤或病变组织因此能争取更多时间发挥自身愈合能力，得以治愈。相关论文发表在最近出版的《公共科学图书馆·综合》上。
“基本上我们是帮干细胞‘隐身’，让体内天然‘杀手’T细胞和免疫系统对它们‘视而不见’，这样它们就能生存下来并促进身体康复。”论文高级作者、研究所再生医学教授格雷卡·阿尔梅达-普拉达解释说，“干细胞天生具有帮助调节免疫反应的能力。如果能增加它们的存活率，理论上就能作为一种治疗措施，降低炎症反应，帮助器官移植病人避免排斥反应等。”
研究使用的是间充质干细胞（MSCs），存在于骨髓、外周血与脐带血、胎儿肝脏和肺等组织中。这些细胞在免疫调节、营养等方面具有特殊性，能优先迁移到受伤的身体组织，促进创伤愈合。但MSCs也像其他细胞一样，容易被身体的免疫系统攻击杀死。
常见病毒是人类巨细胞病毒（HCMV），是疱疹病毒家族的成员之一，能在人体长期潜伏却不使人发病。“我们想利用这种病毒躲避免疫系统的能力。”阿尔梅达-普拉达说，“方法是修改细胞让它们产生和HCMV相同的蛋白质，这样它们就不会被杀死。”
研究人员从人类胎儿肝脏组织中提取了MSCs，通过基因工程让它们也能产生HMCV病毒表达的特殊蛋白质。在此过程中，他们识别出了能最有效地增加细胞存活率的蛋白质——US2蛋白，并首次证明，US2蛋白过度表达会降低免疫系统对细胞的识别能力，使其存活率提高大约59%。
“研究显示，基因修改后的细胞，其存活率大大提高。”阿尔梅达-普拉达说，“下一步，我们希望对它们在治疗肠道疾病、外伤性脑损伤和人类器官移植愈合方面的潜力进行评估。”（生物谷Bioon.com）
DOI： 10.1371/journal.pone.0060461
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Mesenchymal Stem Cells Engineered to Inhibit Complement-Mediated Damage
Melisa A. Soland, et al
Mesenchymal stem cells (MSC) preferentially migrate to damaged tissues and, due to their immunomodulatory and trophic properties, contribute to tissue repair. Although MSC express molecules, such as membrane cofactor protein (CD46), complement decay-accelerating factor (CD55), and protectin (CD59), which confer protection from complement-mediated lysis, MSC are recruited and activated by anaphylatoxins after transplantation, potentially causing MSC death and limiting therapeutic benefit. We have previously demonstrated that transduction of MSC with a retrovirus encoding HCMV-US proteins resulted in higher levels of MSC engraftment due to decreased HLA-I expression. Here, we investigate whether engineering MSC to express US2 (MSC-US2), US3 (MSC-US3), US6 (MSC-US6), or US11 (MSC-US11) HCMV proteins can alter complement recognition, thereby better protecting MSC from complement attack and lysis. HCMV-US proteins increased MSC CD59 expression at different levels as determined by flow cytometric evaluation of the median fluorescence intensity ratio (MFI). A significant increase in CD59 expression was seen in MSC-US2, MSC-US3, and MSC-US6, but not in MSC-US11. Only MSC-US2 displayed increased expression of CD46, while US2 and US3 proteins were both able to augment the percentage of MSC expressing this molecule. Regardless of the HCMV protein expressed, none changed CD55 MFI; however, expression of US6, US11, and US2 each increased the percentage of MSC that were positive for this molecule. Because US2 protein was the most efficient in up-regulating all three complement regulatory proteins, we used a functional complement-mediated cytotoxicity assay to investigate whether MSC-US2 were protected from complement-mediated lysis. We demonstrated that over-expression of the US2 protein reduced complement lysis by 59.10±12.89% when compared to untransduced MSC. This is the first report, to our knowledge, describing a role of HCMV-US proteins in complement evasion, and our data shows that over-expression of US2 protein on MSC could serve as a strategy to protect these cells from complement lysis.
