Huang Bing, Jiang Xin-Chi, Zhang Tian-Yuan, Hu Yu-Lan, Tabata Yasuhiko, Chen Zhong, Pluchino Stefano, Gao Jian-Qing
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, PR China.
Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Int J Pharm. 2017 Oct 5;531(1):90-100. doi: 10.1016/j.ijpharm.2017.08.073. Epub 2017 Aug 18.
Mesenchymal stem cells (MSCs) have been regarded as potential targeting vehicles and demonstrated to exert therapeutic benefits for brain diseases. Direct homing to diseased tissue is crucial for stem cell-based therapy. In this study, a peptide-based targeting approach was established to enhance cell homing to cerebral ischemic lesion. Palmitic acid-peptide painted onto the cell membrane was able to direct MSCs to ischemic tissues without any observed cell cytotoxicity and influence on differentiation, thus reducing accumulation of cells in peripheral organs and increasing engraftment of cells in the targeted tissues. With enhanced cell homing, MSCs were used to deliver miR-133b to increase the expression level of miR-133b in an ischemic lesion and further improve therapeutic effects. This study is the first to develop MSCs co-modified with targeting peptide and microRNAs as potential targeting therapeutic agents. This targeting delivery system is expected to be applicable to other cell types and other diseases aside from stroke.
间充质干细胞（MSCs）已被视为潜在的靶向载体，并已证明对脑部疾病具有治疗作用。直接归巢至患病组织对于基于干细胞的治疗至关重要。在本研究中，建立了一种基于肽的靶向方法，以增强细胞向脑缺血损伤部位的归巢。涂覆在细胞膜上的棕榈酸肽能够将间充质干细胞导向缺血组织，未观察到任何细胞毒性以及对分化的影响，从而减少了细胞在外周器官中的蓄积，并增加了细胞在靶向组织中的植入。随着细胞归巢能力的增强，间充质干细胞被用于递送miR-133b，以提高缺血损伤部位miR-133b的表达水平，并进一步改善治疗效果。本研究首次开发了用靶向肽和微小RNA共同修饰的间充质干细胞作为潜在的靶向治疗剂。这种靶向递送系统有望适用于除中风之外的其他细胞类型和其他疾病。
