藻酸盐水凝胶中间充质干细胞球体的细胞迁移和骨形成受黏附配体密度的调节。
Cell Migration and Bone Formation from Mesenchymal Stem Cell Spheroids in Alginate Hydrogels Are Regulated by Adhesive Ligand Density.
机构信息
Department of Biomedical Engineering, University of California, Davis , Davis California 95616, United States.
Department of Orthopaedic Surgery, UC Davis Health , Sacramento California 95817, United States.
出版信息
Biomacromolecules. 2017 Dec 11;18(12):4331-4340. doi: 10.1021/acs.biomac.7b01366. Epub 2017 Nov 30.
Abstract
The adhesion and migration of cells entrapped in engineered materials is regulated by available adhesive ligands. Although mesenchymal stem cell (MSC) spheroids injected into damaged tissues promote repair, their transplantation in biomaterials which regulate cell migration from the aggregate may further enhance their therapeutic potential. Alginate hydrogels were modified with Arginine-Glycine-Aspartic acid (RGD) at increasing concentrations, and osteogenically induced human MSC spheroids were entrapped to assess cell migration, survival, and differentiation. Cell migration was greater from MSC spheroids in alginate modified with low RGD levels, while the osteogenic potential was higher for spheroids entrapped in unmodified or high RGD density gels in vitro. Upon ectopic implantation, microCT and immunohistochemistry revealed extensive osteogenesis in unmodified and high RGD density gels compared to low RGD density gels. These data suggest that restriction of MSC migration from spheroids correlates with enhanced spheroid osteogenic potential, representing a novel tool for bone tissue engineering.
摘要
细胞外基质中黏附分子的表达水平调节细胞的黏附和迁移。间充质干细胞（MSC）球体注射到受损组织中可促进修复，但将其移植到可调节细胞从聚集物中迁移的生物材料中可能会进一步增强其治疗潜力。用不同浓度的精氨酸-甘氨酸-天冬氨酸（RGD）修饰藻酸盐水凝胶，并包埋成骨诱导的人 MSC 球体，以评估细胞迁移、存活和分化。低 RGD 水平修饰的藻酸盐中 MSC 球体的迁移能力更强，而在未修饰或高 RGD 密度凝胶中包埋的球体的成骨潜力更高。异位植入后，microCT 和免疫组织化学显示，与低 RGD 密度凝胶相比，未修饰和高 RGD 密度凝胶中存在广泛的成骨。这些数据表明，从球体中限制 MSC 迁移与增强球体的成骨潜力相关，为骨组织工程提供了一种新工具。
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