Clinic for Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, Germany.
Division of Plastic, Reconstructive and Aesthetic Surgery, Department of Surgery, University Hospital Bonn, 53127 Bonn, Germany.
Int J Mol Sci. 2020 Mar 27;21(7):2310. doi: 10.3390/ijms21072310.
Currently, there is an increasing focus on mesenchymal stromal cells (MSC) as therapeutic option in bone pathologies as well as in general regenerative medicine. Although human MSCs have been extensively characterized and standardized, ovine MSCs are poorly understood. This limitation hampers clinical progress, as sheep are an excellent large animal model for orthopedic studies. Our report describes a direct comparison of human and ovine MSCs from three corresponding sources under the same conditions. All MSCs presented solid growth behavior and potent immunomodulatory capacities. Additionally, we were able to identify common positive (CD29, CD44, CD73, CD90, CD105, CD166) and negative (CD14, CD34, CD45, HLA-DR) surface markers. Although both human and ovine MSCs showed strong osteogenic potential, direct comparison revealed a slower mineralization process in ovine MSCs. Regarding gene expression level, both human and ovine MSCs presented a comparable up-regulation of Runx2 and a trend toward down-regulation of Col1A during osteogenic differentiation. In summary, this side by side comparison defined phenotypic similarities and differences of human and ovine MSCs from three different sources, thereby contributing to a better characterization and standardization of ovine MSCs. The key findings shown in this report demonstrate the utility of ovine MSCs in preclinical studies for MSC-based therapies.
目前，间充质基质细胞（MSC）作为治疗骨病理学以及一般再生医学的选择越来越受到关注。尽管人类 MSCs 已经得到了广泛的描述和标准化，但绵羊 MSCs 却知之甚少。这种局限性阻碍了临床进展，因为绵羊是骨科研究的优秀大型动物模型。我们的报告描述了在相同条件下，来自三个相应来源的人类和绵羊 MSCs 的直接比较。所有 MSCs 均表现出稳定的生长行为和强大的免疫调节能力。此外，我们能够鉴定常见的阳性（CD29、CD44、CD73、CD90、CD105、CD166）和阴性（CD14、CD34、CD45、HLA-DR）表面标志物。尽管人类和绵羊 MSCs 均具有很强的成骨潜能，但直接比较显示绵羊 MSCs 的矿化过程较慢。关于基因表达水平，在成骨分化过程中，人类和绵羊 MSCs 均表现出 Runx2 的上调和 Col1A 的下调趋势。总之，这种并排比较定义了来自三个不同来源的人类和绵羊 MSCs 的表型相似性和差异，从而有助于更好地描述和标准化绵羊 MSCs。本报告中的关键发现表明绵羊 MSCs 在基于 MSC 的治疗的临床前研究中的实用性。
