Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang, Liaoning 110013, P.R. China.
Shenyang Amnion Biological Engineering Technology Research and Development Center Limited Company, Shenyang, Liaoning 110629, P.R. China.
Int J Mol Med. 2019 Nov;44(5):1629-1640. doi: 10.3892/ijmm.2019.4346. Epub 2019 Sep 20.
Stem cells derived from human amniotic membrane (hAM) are promising targets in regenerative medicine. A previous study focused on human amniotic stem cells in skin wound and scar‑free healing. The present study aimed to investigate whether hydrogen peroxide (H2O2)‑induced senescence of human dermal fibroblasts (hDFs) was influenced by the anti‑aging effect of conditioned medium (CdM) derived from human amniotic stem cells. First, the biological function of two types of amniotic stem cells, namely human amniotic epithelial cells (hAECs) and human amniotic mesenchymal stem cells (hAMSCs), on hDFs was compared. The results of cell proliferation and wound healing assays showed that CdM promoted cell proliferation and migration. In addition, CdM from hAECs and hAMSCs significantly promoted proliferation of senescent hDFs induced by H2O2. These results indicated that CdM protects cells from damage caused by H2O2. Treatment with CdM decreased senescence‑associated β‑galactosidase activity and improved the entry of proliferating cells into the S phase. Simultaneously, it was found that CdM increased the activity of superoxide dismutase and catalase and decreased malondialdehyde by reducing H2O2‑induced intracellular reactive oxygen species production. It was found that CdM downregulated H2O2‑stimulated 8‑hydroxydeoxyguanosine and γ‑H2AX levels and decreased the expression of the senescence‑associated proteins p21 and p16. In conclusion, the findings indicated that the paracrine effects derived from human amniotic stem cells aided delaying oxidative stress‑induced premature senescence.
人羊膜来源的干细胞(hAM)是再生医学中有前途的靶标。先前的研究集中在人羊膜干细胞在皮肤伤口和无疤痕愈合中的作用。本研究旨在探讨过氧化氢(H2O2)诱导的人真皮成纤维细胞(hDFs)衰老是否受人羊膜干细胞条件培养基(CdM)的抗老化作用影响。首先,比较了两种类型的羊膜干细胞,即人羊膜上皮细胞(hAECs)和人羊膜间充质干细胞(hAMSCs)对hDFs的生物学功能。细胞增殖和划痕愈合实验的结果表明,CdM促进了细胞的增殖和迁移。此外,hAECs 和 hAMSCs 的 CdM 显著促进了 H2O2诱导的衰老 hDFs 的增殖。这些结果表明 CdM 保护细胞免受 H2O2 损伤。用 CdM 处理可降低衰老相关的β-半乳糖苷酶活性,并可促进增殖细胞进入 S 期。同时,发现 CdM 通过减少 H2O2 诱导的细胞内活性氧的产生,增加了超氧化物歧化酶和过氧化氢酶的活性,降低了丙二醛的含量。发现 CdM 下调了 H2O2 刺激的 8-羟基脱氧鸟苷和γ-H2AX 水平,并降低了衰老相关蛋白 p21 和 p16 的表达。综上所述,这些发现表明人羊膜干细胞的旁分泌作用有助于延缓氧化应激诱导的过早衰老。