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Abstract：
Due to their unique properties, human mesenchymal stem/stromal cells (MSCs) possess tremendous potential in regenerative medicine, particularly in cell-based therapies where the multipotency and immunomodulatory characteristics of MSCs can be leveraged to address a variety of disease states. Although MSC-based cell therapeutics have emerged as one of the most promising medical treatments, the clinical translation is hampered by the variability of MSC-based cellular products caused by tissue source-specific differences and the lack of physiological cell culture approaches that closely mimic the human cellular microenvironment. In this study, a model for trilineage differentiation of primary adipose-, bone marrow-, and umbilical cord-derived MSCs into adipocytes, chondrocytes and osteoblasts was established and characterized. Differentiation was performed in spheroid culture, using hypoxic conditions and serum-free and antibiotics-free medium. This platform was characterized for spheroid diameter and trilineage differentiation capacity reflecting functionality of differentiated cells, as indicated by lineage-specific extracellular matrix (ECM) accumulation and expression of distinct secreted markers. The presented model shows spheroid growth during the course of differentiation and successfully supports trilineage differentiation for MSCs from almost all tissue sources except for osteogenesis of umbilical cord-derived MSCs. These findings indicate that this platform provides a suitable and favorable environment for trilineage differentiation of MSCs from various tissue sources. Therefore, it poses a promising model to generate highly relevant biological data urgently required for clinical translation and therefore might be used in the future to generate in vitro microtissues, building blocks for tissue engineering or as disease models.
摘要：
由于其独特的性质，人类间充质干细胞/基质细胞（MSCs）在再生医学中具有巨大的潜力，特别是在基于细胞的疗法中，其中可以利用MSC的多能性和免疫调节特征来解决多种疾病状态。尽管基于MSC的细胞疗法已成为最有前途的医学治疗方法之一，由组织来源特异性差异引起的基于MSC的细胞产物的变异性以及缺乏紧密模拟人类细胞微环境的生理细胞培养方法阻碍了临床翻译。在这项研究中,原发性脂肪的三系分化模型-，骨髓-,和脐带来源的MSCs进入脂肪细胞，软骨细胞和成骨细胞的建立和表征。在球状体培养中进行分化，使用低氧条件和无血清和无抗生素的培养基。该平台的特征在于球体直径和三系分化能力，反映了分化细胞的功能。如谱系特异性细胞外基质（ECM）的积累和不同分泌标志物的表达所示。所提供的模型显示了分化过程中的球体生长，并成功地支持了除脐带来源的MSC成骨以外的几乎所有组织来源的MSC的三系分化。这些发现表明该平台为来自各种组织来源的MSC的三系分化提供了合适且有利的环境。因此,它提出了一个有希望的模型，以生成临床翻译迫切需要的高度相关的生物学数据，因此可能在未来用于生成体外微组织，组织工程或疾病模型的构建块。
