Cell Migration and Bone Formation from Mesenchymal Stem Cell Spheroids in Alginate Hydrogels Are Regulated by Adhesive Ligand Density,Biomacromolecules

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Cell Migration and Bone Formation from Mesenchymal Stem Cell Spheroids in Alginate Hydrogels Are Regulated by Adhesive Ligand Density
Biomacromolecules ( IF 5.5 ) Pub Date : 2017-11-30 00:00:00 , DOI: 10.1021/acs.biomac.7b01366
Steve S Ho ₁ , Andrew T Keown ₁ , Bennett Addison ₁ , J Kent Leach _{1,

2}

Affiliation

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.

中文翻译：

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粘附配体密度的调节

工程材料中捕获的细胞的粘附和迁移受到可用的粘附配体的调节。尽管注射到受损组织中的间充质干细胞（MSC）球体可以促进修复，但将其移植到调节细胞从聚集体迁移的生物材料中可能会进一步增强其治疗潜力。用浓度不断增加的精氨酸-甘氨酸-天冬氨酸 (RGD) 修饰藻酸盐水凝胶，并捕获成骨诱导的人 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的 MSC 球体的细胞迁移更大，而体外未修饰或高 RGD 密度凝胶中捕获的球体的成骨潜力更高。异位植入后，显微 CT 和免疫组织化学显示，与低 RGD 密度凝胶相比，未修饰的高 RGD 密度凝胶具有广泛的成骨作用。这些数据表明，MSC 从球体迁移的限制与球体成骨潜力的增强相关，代表了骨组织工程的一种新工具。

更新日期：2017-11-30

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