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

IF 2.9 4区生物学 Q3 CELL BIOLOGY

Journal of Molecular Histology Pub Date : 2025-03-13 DOI:10.1007/s10735-025-10382-x

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

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引用次数: 0

Abstract

We examined whether combined exogenous mitochondria (Ex^Mito) and cellular prion protein overexpression (Ove-PrP^C) in adipose-derived mesenchymal stem cell (Ove-PrP^C 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^Mito 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). PrP^C−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 + Ex^Mito (350 μg) by intracranial injection at 3 h after ICH], 4 [ICH + PrP^C−OE in ADMSCs (6.0 × 10⁵ cells) and intracranial injection and 1.2 × 10⁶ cells by intravenous injection)], and 5 (ICH + combined Ex^Mito + PrP^C−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 Ex^Mito + PrP^C−OE ADMSCs therapy was superior to either therapy alone in mitigating the ICH-induced brain damage.

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外源性线粒体增加了脂肪源性间充质干细胞治疗颅内出血大鼠细胞朊蛋白过表达的益处

我们研究了外源性线粒体（ExMito）和细胞朊蛋白过表达（Ove-PrPC）在脂肪源性间充质干细胞（Ove-PrPC in ADMSCs）中的联合治疗是否优于单一治疗，以保护大鼠免受颅内出血（ICH）。在体外，与对照组相比，缺氧条件下ExMito输注受体细胞（即N2a细胞）显著增加（P < 0.001）， ρ0细胞增殖和细胞周期激活增强（P < 0.001）。与ADMSCs相比，ADMSCs中的PrPC−OE对h2o2诱导的细胞衰老、线粒体和DNA损伤具有更高的抵抗力（P < 0.001）。将大鼠分为1组（假对照）、2组（ICH）、3组(ICH + ExMito （350 μg，颅内注射）、4组（ICH + ADMSCs中PrPC−OE （6.0 × 105个细胞）、颅内注射和静脉注射1.2 × 106个细胞）、5组（ICH + ADMSCs中ExMito + PrPC−OE联合）。第28天，脑梗死体积、脑梗死面积、炎症细胞浸润、DNA和线粒体损伤生物标志物以2组最高，1组最低，5组显著低于3组和4组。NeuN细胞在脑梗死体积上表现出相反的模式，神经功能（角点测试）在3组和4组显著改善，5组比2组进一步改善（P < 0.0001）。ExMito + PrPC−OE ADMSCs联合治疗在减轻ich诱导的脑损伤方面优于单独治疗。

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来源期刊

Journal of Molecular Histology 生物-细胞生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.