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通过阿仑膦酸盐功能化纳米粒子向骨靶向递送 SDF-1 以引导干细胞迁移。

Bone Targeted Delivery of SDF-1 via Alendronate Functionalized Nanoparticles in Guiding Stem Cell Migration.

机构信息

Research Center for Human Tissues and Organs Degeneration, Institute of Biomedicine and Biotechnology , Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen , 518055 , PR China.

School of Pharmaceutical Science , Guangzhou Medical University , Guangzhou , Guangdong , 511436 , PR China.

出版信息

ACS Appl Mater Interfaces. 2018 Jul 18;10(28):23700-23710. doi: 10.1021/acsami.8b08606. Epub 2018 Jul 6.

DOI:10.1021/acsami.8b08606
PMID:29939711
Abstract

Stem cells are well-known for their great capacity for tissue regeneration. This provides a promising source for cell-based therapies in treating various bone degenerative disorders. However, the major hurdles for their application in transplantation are the poor bone marrow homing and engraftment efficiencies. Stromal cell-derived factor 1 (SDF-1) has been identified as a major stem cell homing factor. With the aims of bone targeted SDF-1 delivery and regulating MSCs migration, alendronate modified liposomal nanoparticles (Aln-Lipo) carrying SDF-1 gene were developed in this study. Alendronate modification significantly increased the mineral binding affinity of liposomes, and facilitated the gene delivery to osteoblastic cells. Up-regulated SDF-1 expression in osteoblasts triggered MSCs migration. Systemic infusion of Aln-Lipo-SDF-1 with fluorescence labeling in mice showed the accumulation in osseous tissue by biophotonic imaging. Corresponding to the delivered SDF-1, the transplanted GFP MSCs were attracted to bone marrow and contributed to bone regeneration. This study may provide a useful technique in regulating stem cell migration.

摘要

干细胞以其强大的组织再生能力而闻名。这为基于细胞的疗法治疗各种骨退行性疾病提供了有希望的来源。然而,它们在移植应用中的主要障碍是骨髓归巢和植入效率差。基质细胞衍生因子 1(SDF-1)已被确定为主要的干细胞归巢因子。本研究旨在通过骨靶向 SDF-1 递送来调节间充质干细胞的迁移,开发了携带 SDF-1 基因的阿仑膦酸钠修饰的脂质体纳米颗粒(Aln-Lipo)。阿仑膦酸钠修饰显著增加了脂质体的矿化结合亲和力,并促进了基因向成骨细胞的传递。成骨细胞中 SDF-1 的上调表达触发了间充质干细胞的迁移。通过生物光子成像在携带荧光标记的小鼠中进行的 Aln-Lipo-SDF-1 全身输注显示了在骨组织中的积累。与递送的 SDF-1 相对应,移植的 GFP 间充质干细胞被吸引到骨髓中,并有助于骨再生。这项研究可能为调节干细胞迁移提供了一种有用的技术。

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