Scholarlink

<p>We examined whether combined exogenous mitochondria (Ex<sup>Mito</sup>) and cellular prion protein overexpression (Ove-PrP<sup>C</sup>) in adipose-derived mesenchymal stem cell (Ove-PrP<sup>C</sup> in ADMSCs) therapy is superior to a single therapy for protecting the brain against intracranial hemorrhage (ICH) in rats. In vitro, compared with the control group, Ex<sup>Mito</sup> transfusion into recipient cells (i.e., N2a cells) significantly increased under hypoxic conditions (<i>P</i> &lt; 0.001) and augmented ρ0 cell proliferation and cell-cycle activation (<i>P</i> &lt; 0.001). PrP<sup>C−OE</sup> in ADMSCs exhibited higher resistance to H<sub>2</sub>O<sub>2</sub>-induced cell senescence and mitochondrial and DNA damage compared to ADMSCs (<i>P</i> &lt; 0.001). Rats were categorized into group 1 (sham-control), 2 (ICH), 3 [ICH + Ex<sup>Mito</sup> (350&#xa0;μg) by intracranial injection at 3&#xa0;h after ICH], 4 [ICH + PrP<sup>C−OE</sup> in ADMSCs (6.0 × 10<sup>5</sup> cells) and intracranial injection and 1.2 × 10<sup>6</sup> cells by intravenous injection)], and 5 (ICH + combined Ex<sup>Mito</sup> + PrP<sup>C−OE</sup> in ADMSCs). By day 28, the brain infarct volume, brain infarct area, inflammatory cell infiltration, and biomarkers for DNA and mitochondrial damage were highest in group 2, lowest in group 1, and significantly lower in group 5 than in groups 3 and 4. NeuN cells exhibited the opposite pattern for brain infarct volume, and neurological function (corner test) significantly improved in groups 3 and 4, with further improvement in group 5 compared with that in group 2 (<i>P</i> &lt; 0.0001). Combined Ex<sup>Mito</sup> + PrP<sup>C−OE</sup> ADMSCs therapy was superior to either therapy alone in mitigating the ICH-induced brain damage.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Exogenous mitochondria added on benefits for cellular prion protein overexpression in adipose-derived mesenchymal stem cells treatment on intracranial hemorrhage rat

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月13日

查看全文
  • Kun-Chen Lin,
  • Jui-Ning Yeh,
  • Pei‐Hsun Sung,
  • Tsung-Cheng Yin,
  • John Y. Chiang,
  • Chi-Ruei Huang,
  • Yi-Ling Chen,
  • Yi-Ting Wang,
  • Kuan-Hung Chen,
  • Hon‐Kan Yip

摘要

We examined whether combined exogenous mitochondria (ExMito) and cellular prion protein overexpression (Ove-PrPC) in adipose-derived mesenchymal stem cell (Ove-PrPC in ADMSCs) therapy is superior to a single therapy for protecting the brain against intracranial hemorrhage (ICH) in rats. In vitro, compared with the control group, ExMito transfusion into recipient cells (i.e., N2a cells) significantly increased under hypoxic conditions (P < 0.001) and augmented ρ0 cell proliferation and cell-cycle activation (P < 0.001). PrPC−OE in ADMSCs exhibited higher resistance to H2O2-induced cell senescence and mitochondrial and DNA damage compared to ADMSCs (P < 0.001). Rats were categorized into group 1 (sham-control), 2 (ICH), 3 [ICH + ExMito (350 μg) by intracranial injection at 3 h after ICH], 4 [ICH + PrPC−OE in ADMSCs (6.0 × 105 cells) and intracranial injection and 1.2 × 106 cells by intravenous injection)], and 5 (ICH + combined ExMito + PrPC−OE in ADMSCs). By day 28, the brain infarct volume, brain infarct area, inflammatory cell infiltration, and biomarkers for DNA and mitochondrial damage were highest in group 2, lowest in group 1, and significantly lower in group 5 than in groups 3 and 4. NeuN cells exhibited the opposite pattern for brain infarct volume, and neurological function (corner test) significantly improved in groups 3 and 4, with further improvement in group 5 compared with that in group 2 (P < 0.0001). Combined ExMito + PrPC−OE ADMSCs therapy was superior to either therapy alone in mitigating the ICH-induced brain damage.