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首页> 外文期刊>Cell and Tissue Research >Human mesenchymal stem cell spheroids in fibrin hydrogels exhibit improved cell survival and potential for bone healing
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Human mesenchymal stem cell spheroids in fibrin hydrogels exhibit improved cell survival and potential for bone healing

机译：纤维蛋白水凝胶中的人间充质干细胞球体具有改善的细胞存活率和骨愈合潜力

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Mesenchymal stem cells (MSCs) have great therapeutic potential for the repair of nonhealing bone defects, because of their proliferative capacity, multilineage potential, trophic factor secretion and lack of immunogenicity. However, a major challenge to the translation of cell-based therapies into clinical practice is ensuring their survival and function upon implantation into the defect site. We hypothesize that forming MSCs into more physiologic three-dimensional spheroids, rather than employing dissociated cells from two-dimensional monolayer culture, will enhance their survival when exposed to a harsh microenvironment but maintain their osteogenic potential. MSC spheroids were formed by using the hanging drop method with increasing cell numbers. Compared with larger spheroids, the smallest spheroids, which contained 15,000 cells, exhibited increased metabolic activity, reduced apoptosis and the most uniform distribution of proliferating cells. Spheroids were then entrapped in fibrin gels and cultured in serum-free medium and 1 % oxygen. Compared with identical numbers of dissociated MSCs in fibrin gels, spheroids exhibited significantly reduced apoptosis and secreted up to 100-fold more vascular endothelial growth factor. Moreover, fibrin gels containing spheroids and those containing an equivalent number of dissociated cells exhibited similar expression levels of early and late markers of osteogenic differentiation. Thus, MSC spheroids exhibit greater resistance to apoptosis and enhanced proangiogenic potential while maintaining similar osteogenic potential to dissociated MSCs entrapped in a clinically relevant biomaterial, supporting the use of MSC spheroids in cell-based approaches to bone repair.
机译：间充质干细胞（MSCs）具有增殖能力，多谱系潜能，营养因子分泌和缺乏免疫原性等特点，具有修复骨不愈合的巨大治疗潜力。然而，将基于细胞的疗法转化为临床实践的主要挑战是确保其在植入缺损部位后的存活和功能。我们假设，将MSC形成更多的生理性三维球体，而不是使用二维单层培养的解离细胞，可以在暴露于恶劣的微环境时提高其存活率，但仍能保持其成骨潜力。 MSC球体通过使用悬滴法形成，细胞数增加。与较大的球体相比，包含15,000个细胞的最小的球体具有更高的代谢活性，减少的细胞凋亡和最均匀的增殖细胞分布。然后将球状体包裹在纤维蛋白凝胶中，并在无血清的培养基和1％的氧气中培养。与纤维蛋白凝胶中相同数量的解离的MSC相比，球体的细胞凋亡显着减少，并且分泌的血管内皮生长因子最多高100倍。此外，含有球状蛋白和含等量解离细胞的纤维蛋白凝胶在成骨分化的早期和晚期标记物上的表达水平相似。因此，MSC球体对细胞凋亡具有更大的抵抗力，并增强了促血管生成的潜力，同时保持了与临床相关生物材料中截留的解离MSC相似的成骨潜能，从而支持了MSC球体在基于细胞的骨修复方法中的使用。

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