Laboratory for Stem Cells, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
Omnion Research International, Zagreb, Croatia.
Cell Mol Neurobiol. 2023 Jul;43(5):1975-1988. doi: 10.1007/s10571-022-01276-7. Epub 2022 Sep 9.
The success rate of regenerative medicine largely depends on the type of stem cells applied in such procedures. Consequently, to achieve the needed level for clinical standardization, we need to investigate the viability of accessible sources with sufficient quantity of cells. Since the oral region partly originates from the neural crest, which naturally develops in niche with decreased levels of oxygen, the main goal of this work was to test if human oral mucosa stem cells (hOMSC) might be used to treat neurons damaged by anoxia. Here we show that hOMSC are more resistant to anoxia than human induced pluripotent stem cells and that they secrete BDNF, GDNF, VEGF and NGF. When hOMSC were added to human neurons damaged by anoxia, they significantly improved their survival. This regenerative capability was at least partly achieved through miR-514A-3p and SHP-2 and it decreased in hOMSC exposed to neural cells for 14 or 28 days. In addition, the beneficial effect of hOMSC were also confirmed in mice affected by stroke. Hence, in this work we have confirmed that hOMSC, in a time-limited manner, improve the survival of anoxia-damaged neurons and significantly contribute to the recovery of experimental animals following stroke.
再生医学的成功率在很大程度上取决于应用于此类程序的干细胞类型。因此，为了达到临床标准化所需的水平，我们需要研究具有足够数量细胞的可及来源的可行性。由于口腔区域部分来源于神经嵴，而神经嵴在低氧水平的龛位中自然发育，因此这项工作的主要目标是测试人口腔黏膜干细胞（hOMSC）是否可用于治疗因缺氧而受损的神经元。在这里，我们发现 hOMSC 比人诱导多能干细胞对缺氧更具抗性，并且它们分泌 BDNF、GDNF、VEGF 和 NGF。当将 hOMSC 添加到因缺氧而受损的人神经元中时，它们显著提高了神经元的存活率。这种再生能力至少部分是通过 miR-514A-3p 和 SHP-2 实现的，并且在暴露于神经细胞 14 或 28 天的 hOMSC 中降低了。此外，hOMSC 的有益作用在患有中风的小鼠中也得到了证实。因此，在这项工作中，我们已经证实 hOMSC 可以在有限的时间内提高缺氧损伤神经元的存活率，并显著促进中风后实验动物的恢复。
