Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Donaueschingenstraße 13, 1200 Vienna, Austria.
Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria.
Cells. 2019 Dec 15;8(12):1641. doi: 10.3390/cells8121641.
Amniotic cells show exciting stem cell features, which has led to the idea of using living cells of human amniotic membranes (hAMs) in toto for clinical applications. However, under common cell culture conditions, viability of amniotic cells decreases rapidly, whereby reasons for this decrease are unknown so far. Recently, it has been suggested that loss of tissue tension in vivo leads to apoptosis. Therefore, the aim of this study was to investigate the effect of tissue distention on the viability of amniotic cells in vitro. Thereby, particular focus was put on vital mitochondria-linked parameters, such as respiration and ATP synthesis. Biopsies of hAMs were incubated for 7-21 days either non-distended or distended. We observed increased B-cell lymphoma 2-associated X protein (BAX)/B-cell lymphoma (BCL)-2 ratios in non-distended hAMs at day seven, followed by increased caspase 3 expression at day 14, and, consequently, loss of viability at day 21. In contrast, under distention, caspase 3 expression increased only slightly, and mitochondrial function and cellular viability were largely maintained. Our data suggest that a mechano-sensing pathway may control viability of hAM cells by triggering mitochondria-mediated apoptosis upon loss of tension in vitro. Further studies are required to elucidate the underlying molecular mechanisms between tissue distention and viability of hAM cells.
羊膜细胞表现出令人兴奋的干细胞特征,这使得人们产生了将完整的人羊膜(hAMs)活细胞用于临床应用的想法。然而,在常见的细胞培养条件下,羊膜细胞的存活率会迅速下降,目前尚不清楚导致这种下降的原因。最近有人提出,体内组织张力的丧失会导致细胞凋亡。因此,本研究旨在探讨组织扩张对体外羊膜细胞活力的影响。因此,特别关注了与线粒体相关的重要参数,如呼吸和 ATP 合成。将 hAMs 活检标本在未扩张或扩张的情况下孵育 7-21 天。我们观察到,在未扩张的 hAMs 中,第 7 天 B 细胞淋巴瘤 2 相关 X 蛋白(BAX)/B 细胞淋巴瘤(BCL)-2 比值增加,随后第 14 天 caspase 3 表达增加,最终第 21 天活力丧失。相比之下,在扩张条件下,caspase 3 的表达仅略有增加,线粒体功能和细胞活力基本保持不变。我们的数据表明,机械感应途径可能通过在体外失去张力时触发线粒体介导的细胞凋亡来控制 hAM 细胞的活力。需要进一步的研究来阐明组织扩张与 hAM 细胞活力之间的潜在分子机制。