Teixeira Fábio G, Panchalingam Krishna M, Anjo Sandra Isabel, Manadas Bruno, Pereira Ricardo, Sousa Nuno, Salgado António J, Behie Leo A
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Stem Cell Res Ther. 2015 Jul 24;6(1):133. doi: 10.1186/s13287-015-0124-z.
The use of human umbilical cord Wharton Jelly-derived mesenchymal stem cells (hWJ-MSCs) has been considered a new potential source for future safe applications in regenerative medicine. Indeed, the application of hWJ-MSCs into different animal models of disease, including those from the central nervous system, has shown remarkable therapeutic benefits mostly associated with their secretome. Conventionally, hWJ-MSCs are cultured and characterized under normoxic conditions (21 % oxygen tension), although the oxygen levels within tissues are typically much lower (hypoxic) than these standard culture conditions. Therefore, oxygen tension represents an important environmental factor that may affect the performance of mesenchymal stem cells in vivo. However, the impact of hypoxic conditions on distinct mesenchymal stem cell characteristics, such as the secretome, still remains unclear.
In the present study, we have examined the effects of normoxic (21 % O2) and hypoxic (5 % O2) conditions on the hWJ-MSC secretome. Subsequently, we address the impact of the distinct secretome in the neuronal cell survival and differentiation of human neural progenitor cells.
The present data indicate that the hWJ-MSC secretome collected from normoxic and hypoxic conditions displayed similar effects in supporting neuronal differentiation of human neural progenitor cells in vitro. However, proteomic analysis revealed that the use of hypoxic preconditioning led to the upregulation of several proteins within the hWJ-MSC secretome.
Our results suggest that the optimization of parameters such as hypoxia may lead to the development of strategies that enhance the therapeutic effects of the secretome for future regenerative medicine studies and applications.
人脐带华通氏胶间充质干细胞（hWJ-MSCs）的应用被认为是再生医学未来安全应用的一种新的潜在来源。事实上，将hWJ-MSCs应用于不同的疾病动物模型，包括中枢神经系统疾病模型，已显示出显著的治疗益处，这主要与其分泌组有关。传统上，hWJ-MSCs在常氧条件（21%氧张力）下进行培养和表征，尽管组织内的氧水平通常比这些标准培养条件低得多（低氧）。因此，氧张力是一个可能影响间充质干细胞体内性能的重要环境因素。然而，低氧条件对不同间充质干细胞特性（如分泌组）的影响仍不清楚。
在本研究中，我们研究了常氧（21% O₂）和低氧（5% O₂）条件对hWJ-MSC分泌组的影响。随后，我们探讨了不同分泌组对人神经祖细胞神经元细胞存活和分化的影响。
目前的数据表明，在常氧和低氧条件下收集的hWJ-MSC分泌组在体外支持人神经祖细胞神经元分化方面显示出相似的效果。然而，蛋白质组学分析显示，低氧预处理导致hWJ-MSC分泌组中几种蛋白质上调。
我们的结果表明，优化诸如低氧等参数可能会促成一些策略的开发，这些策略可增强分泌组在未来再生医学研究和应用中的治疗效果。
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