Development of a peptide-targeted, myocardial ischemia-homing, mesenchymal stem cell.
Development of a peptide-targeted, myocardial ischemia-homing, mesenchymal stem cell.
复制标题
DOI：
10.3109/1061186x.2011.622398
复制
发表时间：
2012-01
影响因子：
4.5
通讯作者：
Dennis, James E.
中科院分区：
文献类型：
--
作者：
Kean, Thomas J.;Duesler, Lori;Young, Randell G.;Dadabayev, Alisher;Olenyik, Andrey;Penn, Marc;Wagner, Joseph;Fink, David J.;Caplan, Arnold I.;Dennis, James E.
关键词：
将干细胞定向到心脏对于产生有效的心肌梗死（MI）细胞疗法至关重要。间充质干细胞（MSC）提供了一个精致的药物输送平台，具有环境敏感的细胞因子释放和MSC已显示出治疗MI的潜力。基于肽的靶向提供了一种增加细胞归巢的新方法，其中通过噬菌体展示鉴定的MI特异性肽与棕榈酸尾合成以促进细胞膜整合。在小鼠MI模型中筛选噬菌体肽，并选择四种肽（CRPPR、CRKDKC、KSTRKS和CARSKNKDC）并合成为棕榈酸酯衍生物用于进一步研究。优化细胞包被，并评价包被持久性和细胞毒性。将MSC用肽包被，注射到患有MI的小鼠中，并定量心脏中的MSC。与未涂覆的对照相比，在用肽涂覆的MSC处理的动物的心脏中发现更多数量的MSC。在肽包被的细胞中，MSC数量与MI严重程度呈正相关，但在单独的MSC中呈负相关。已经开发了一种瞬时细胞包被（“涂敷”）方法，其有效地、无毒地标记细胞并增加MI心脏中的细胞定位。
Directing stem cells to the heart is critical in producing an effective cell therapy for myocardial infarction (MI). Mesenchymal stem cells (MSCs) offer an exquisite drug delivery platform with environment-sensing cytokine release and MSCs have shown therapeutic potential in MI. Peptide-based targeting offers a novel method to increase cell homing, wherein MI-specific peptides, identified by phage display, are synthesized with a palmitic acid tail to facilitate cell membrane integration. Phage-peptides were screened in a mouse MI model and four peptides (CRPPR, CRKDKC, KSTRKS, and CARSKNKDC) were selected and synthesized as palmitated derivatives for further investigation. Cell coating was optimized and coating persistence and cytotoxicity were evaluated. MSCs were coated with peptides, injected into mice with MI, and MSCs in the heart quantified. Greater numbers of MSCs were found in heart of animals treated with the peptide-coated MSCs compared to uncoated controls. MSC numbers had positive correlation with MI severity in peptide-coated cells but a negative correlation in MSCs alone. A transient cell coating (“painting”) method has been developed that labels cells efficiently, non-toxically and increases cell localization in MI hearts.