Characterization and Comparison of Human and Ovine Mesenchymal Stromal Cells from Three Corresponding Sources

Characterization and Comparison of Human and Ovine Mesenchymal Stromal Cells from Three Corresponding Sources
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DOI:
10.3390/ijms21072310
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发表时间:
2020-04-01
影响因子:
5.6
通讯作者:
Schildberg, Frank A.
Schildberg, Frank A.
中科院分区:
生物学2区
文献类型:
--
作者:
Haddouti, El-Mustapha;Randau, Thomas M.;Schildberg, Frank A.

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目前,人们越来越关注间充质间质细胞(MSC)作为骨病理和一般再生医学的治疗选择。虽然人类间充质干细胞已经被广泛地表征和标准化,但绵羊间充质干细胞却知之甚少。这一限制阻碍了临床进展,因为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和羊间充质干细胞的直接比较。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,我们能够识别常见的阳性(CD29, CD44, CD73, CD90, CD105, CD166)和阴性(CD14, CD34, CD45, HLA-DR)表面标记物。虽然人和羊间充质干细胞都显示出强大的成骨潜能,但直接比较显示,羊间充质干细胞的矿化过程较慢。在基因表达水平上,人和羊间充质干细胞在成骨分化过程中均表现出Runx2上调和Col1A下调的趋势。总之,这种并排比较确定了来自三种不同来源的人和羊间充质干细胞的表型相似性和差异性,从而有助于更好地表征和标准化羊间充质干细胞。本报告中显示的主要发现证明了羊间充质干细胞在基于间充质干细胞的治疗的临床前研究中的实用性。
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.