Reseach center of Spine Surgery, Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Department of Spine Surgery, Yijishan Hospital, The First Affliated Hospital of Wannan Medical College, Wuhu, Anhui, 241001, China.
Reseach center of Spine Surgery, Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Department of Spine Surgery, Yijishan Hospital, The First Affliated Hospital of Wannan Medical College, Wuhu, Anhui, 241001, China.
Life Sci. 2021 Feb 15;267:118929. doi: 10.1016/j.lfs.2020.118929. Epub 2021 Jan 11.
To investigate if the modification of human adipose-derived mesenchymal stem cells (hADSCs) by the antioxidants superoxide dismutase 2 (Sod2) and catalase (Cat) can attenuate the pathological conditions of intervertebral disc degeneration (IVD).
In vitro, MTT assay and qRT-PCR was used to detect cell proliferation and gene expressions in hADSCs transduced with Ad-null (an adenovirus vector containing no transgene expression cassette), Ad-Sod2 (recombinant adenovirus Sod2) and Ad-Cat. IVD mouse models were generated by needle puncture and treated with hADSCs with/without Ad-null/Ad-Sod2/Ad-Cat. X-ray evaluation, magnetic resonance imaging (MRI) analysis, histological analysis, immunohistochemistry, Western blots, ELISAs and qRT-PCR were performed.
hADSCs transduced with Ad-Sod2 and Ad-Cat showed enhanced cell proliferation with the upregulation of SOX9, ACAN, and COL2. In vivo, IVD mice injected with hADSCs showed increased disc height index, MRI index and mean T2 intensities, as well as the attenuated histologic grading of the annulus fibrosus (AF) and NP accompanied by the upregulation of GAG and COL2, which were further improved in the Ad-Sod2 hADSC + IVD and Ad-Cat hADSC + IVD groups. Furthermore, the increased expression of IL-1β, IL-6 and TNF-α was reduced in IVD mice injected with hADSCs. Compared with the hADSC + IVD group, the Ad-Sod2 hADSC/Ad-Cat hADSC + IVD groups had lower expression of pro-inflammatory factors.
Modification of hADSCs by the antioxidants Sod2 and Cat improved the pathological condition of intervertebral disc tissues with increased GAG and COL2 expression, as well as reduced inflammation, thereby demonstrating a therapeutic effect in IVD.
研究抗氧化酶超氧化物歧化酶 2（Sod2）和过氧化氢酶（Cat）修饰人脂肪间充质干细胞（hADSCs）是否可以减轻椎间盘退变（IVD）的病理状态。
体外采用 MTT 检测和 qRT-PCR 检测转染 Ad-null（不含转基因表达盒的腺病毒载体）、Ad-Sod2（重组腺病毒 Sod2）和 Ad-Cat 的 hADSCs 的细胞增殖和基因表达。通过针刺建立 IVD 小鼠模型，并分别用 hADSCs 联合/不联合 Ad-null/Ad-Sod2/Ad-Cat 进行处理。进行 X 射线评估、磁共振成像（MRI）分析、组织学分析、免疫组织化学、Western blot、ELISA 和 qRT-PCR。
转染 Ad-Sod2 和 Ad-Cat 的 hADSCs 表现出增强的细胞增殖，同时 Sox9、ACAN 和 COL2 的表达上调。在体内，注射 hADSCs 的 IVD 小鼠显示出椎间盘高度指数、MRI 指数和平均 T2 强度增加，以及纤维环（AF）和 NP 的组织学分级降低，伴随着 GAG 和 COL2 的上调，在 Ad-Sod2 hADSC+IVD 和 Ad-Cat hADSC+IVD 组中进一步改善。此外，注射 hADSCs 的 IVD 小鼠中 IL-1β、IL-6 和 TNF-α 的表达增加得到减少。与 hADSC+IVD 组相比，Ad-Sod2 hADSC/Ad-Cat hADSC+IVD 组的促炎因子表达水平较低。
抗氧化酶 Sod2 和 Cat 修饰 hADSCs 可改善椎间盘组织的病理状态，增加 GAG 和 COL2 的表达，同时减少炎症，从而在 IVD 中显示出治疗效果。
