• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

诱导多能干细胞源性间充质干细胞中 miR-19a 和 miR-20a 的双重过表达可有效保护扩张型心肌病大鼠的左心室功能。

Double overexpression of miR-19a and miR-20a in induced pluripotent stem cell-derived mesenchymal stem cells effectively preserves the left ventricular function in dilated cardiomyopathic rat.

机构信息

Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan.

Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, 123, Dapi Road, Niaosung Dist, Kaohsiung, 83301, Taiwan.

出版信息

Stem Cell Res Ther. 2021 Jun 29;12(1):371. doi: 10.1186/s13287-021-02440-4.

DOI:10.1186/s13287-021-02440-4
PMID:34187571
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8243466/
Abstract

BACKGROUND

This study tested the hypothesis that double overexpression of miR-19a and miR-20a (dOex-mIRs) in human induced pluripotent stem cell (iPS)-derived mesenchymal stem cells (MSCs) effectively preserved left ventricular ejection fraction (LVEF) in dilated cardiomyopathy (DCM) (i.e., induced by doxorubicin) rat.

METHODS AND RESULTS

In vitro study was categorized into groups G1 (iPS-MSC), G2 (iPS-MSC), G3 (iPS-MSC + HO/100uM), and G4 (iPS-MSC + HO/100uM). The in vitro results showed the cell viability was significantly lower in G3 than in G1 and G2, and that was reversed in G4 but it showed no difference between G1/G2 at time points of 6 h/24 h/48 h, whereas the flow cytometry of intra-cellular/mitochondrial oxidative stress (DCFA/mitoSOX) and protein expressions of mitochondrial-damaged (cytosolic-cytochrome-C/DRP1/Cyclophilin-D), oxidative-stress (NOX-1/NOX2), apoptotic (cleaved-caspase-3/PARP), fibrotic (p-Smad3/TGF-ß), and autophagic (ratio of LC3B-II/LC3BI) biomarkers exhibited an opposite pattern of cell-proliferation rate (all p< 0.001). Adult-male SD rats (n=32) were equally divided into groups 1 (sham-operated control), 2 (DCM), 3 (DCM + iPS-MSCs/1.2 × 10 cells/administered by post-28 day's DCM induction), and 4 (DCM + iPS-MSC/1.2 × 10 cells/administered by post-28 day's DCM induction) and euthanized by day 60 after DCM induction. LV myocardium protein expressions of oxidative-stress signaling (p22-phox/NOX-1/NOX-2/ASK1/p-MMK4,7/p-JNK1,2/p-cJUN), upstream (TLR-4/MAL/MyD88/TRIF/TRAM/ TFRA6/IKK/NF-κB) and downstream (TNF-α/IL-1ß/MMP-9) inflammatory signalings, apoptotic (cleaved-PARP/mitochondrial-Bax), fibrotic (Smad3/TGF-ß), mitochondrial-damaged (cytosolic-cytochrome-C/DRP1/cyclophilin-D), and autophagic (beclin1/Atg5) biomarkers were highest in group 2, lowest in group 1 and significantly lower in group 4 than in group 3, whereas the LVEF exhibited an opposite pattern of oxidative stress (all p< 0.0001).

CONCLUSION

iPS-MSC therapy was superior to iPS-MSC therapy for preserving LV function in DCM rat.

摘要

背景

本研究旨在检验 miR-19a 和 miR-20a 双重过表达（dOex-mIRs）在人诱导多能干细胞（iPS）衍生的间充质干细胞（MSCs）中是否能有效保留阿霉素诱导的扩张型心肌病（DCM）大鼠的左心室射血分数（LVEF）。

方法和结果

体外研究分为 G1（iPS-MSC）、G2（iPS-MSC）、G3（iPS-MSC+HO/100μM）和 G4（iPS-MSC+HO/100μM）组。体外结果显示，G3 组细胞活力明显低于 G1 组和 G2 组，而 G4 组则逆转，但在 6 h/24 h/48 h 时，G1/G2 之间无差异，而细胞内/线粒体氧化应激（DCFA/mitoSOX）的流式细胞术和线粒体损伤（胞质细胞色素-C/DRP1/环胞素-D）、氧化应激（NOX-1/NOX2）、凋亡（cleaved-caspase-3/PARP）、纤维化（p-Smad3/TGF-β）和自噬（LC3B-II/LC3BI 比值）生物标志物的蛋白表达呈现出与细胞增殖率相反的模式（均 p<0.001）。成年雄性 SD 大鼠（n=32）等分为 4 组：1 组（假手术对照）、2 组（DCM）、3 组（DCM+iPS-MSCs/1.2×106 个细胞/在 DCM 诱导后 28 天给药）和 4 组（DCM+iPS-MSCs/1.2×106 个细胞/在 DCM 诱导后 28 天给药），并在 DCM 诱导后 60 天处死。LV 心肌氧化应激信号（p22-phox/NOX-1/NOX-2/ASK1/p-MMK4,7/p-JNK1,2/p-cJUN）、上游（TLR-4/MAL/MyD88/TRIF/TRAM/TFRA6/IKK/NF-κB）和下游（TNF-α/IL-1β/MMP-9）炎症信号、凋亡（cleaved-PARP/线粒体-Bax）、纤维化（Smad3/TGF-β）、线粒体损伤（胞质细胞色素-C/DRP1/环胞素-D）和自噬（beclin1/Atg5）生物标志物在 2 组中最高，在 1 组中最低，在 4 组中明显低于 3 组，而左心室射血分数（LVEF）则呈现出与氧化应激相反的模式（均 p<0.0001）。

结论

iPS-MSC 治疗优于 iPS-MSC 治疗，可保留 DCM 大鼠的 LV 功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/28636d36d791/13287_2021_2440_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/c0740c6c2ec4/13287_2021_2440_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/4b972cdfc978/13287_2021_2440_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/787072fa04ee/13287_2021_2440_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/2b74bf504b63/13287_2021_2440_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/eb8b2ccea917/13287_2021_2440_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/ebc53efc657e/13287_2021_2440_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/4eb5cad02b5d/13287_2021_2440_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/65523bfe44f8/13287_2021_2440_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/15c1a7acce78/13287_2021_2440_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/18b1e6afcc75/13287_2021_2440_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/28636d36d791/13287_2021_2440_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/c0740c6c2ec4/13287_2021_2440_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/4b972cdfc978/13287_2021_2440_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/787072fa04ee/13287_2021_2440_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/2b74bf504b63/13287_2021_2440_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/eb8b2ccea917/13287_2021_2440_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/ebc53efc657e/13287_2021_2440_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/4eb5cad02b5d/13287_2021_2440_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/65523bfe44f8/13287_2021_2440_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/15c1a7acce78/13287_2021_2440_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/18b1e6afcc75/13287_2021_2440_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ae/8243466/28636d36d791/13287_2021_2440_Fig11_HTML.jpg

相似文献

1
Double overexpression of miR-19a and miR-20a in induced pluripotent stem cell-derived mesenchymal stem cells effectively preserves the left ventricular function in dilated cardiomyopathic rat.诱导多能干细胞源性间充质干细胞中 miR-19a 和 miR-20a 的双重过表达可有效保护扩张型心肌病大鼠的左心室功能。
Stem Cell Res Ther. 2021 Jun 29;12(1):371. doi: 10.1186/s13287-021-02440-4.
2
Early treatment with combination of SS31 and entresto effectively preserved the heart function in doxorubicin-induced dilated cardiomyopathic rat.SS31 与恩格列净联合早期治疗可有效保护阿霉素诱导扩张型心肌病大鼠的心脏功能。
Biomed Pharmacother. 2021 Sep;141:111886. doi: 10.1016/j.biopha.2021.111886. Epub 2021 Aug 10.
3
Early and Dose-Dependent Xenogeneic Mesenchymal Stem Cell Therapy Improved Outcomes in Acute Respiratory Distress Syndrome Rodent Through Ameliorating Inflammation, Oxidative Stress, and Immune Reaction.早期和剂量依赖性异种间充质干细胞治疗通过改善炎症、氧化应激和免疫反应改善急性呼吸窘迫综合征大鼠的预后。
Cell Transplant. 2023 Jan-Dec;32:9636897231190178. doi: 10.1177/09636897231190178.
4
Overexpression of miR-19a and miR-20a in iPS-MSCs preserves renal function of chronic kidney disease with acute ischaemia-reperfusion injury in rat.miR-19a 和 miR-20a 在 iPS-MSCs 中的过表达可保护大鼠慢性肾脏病伴急性缺血再灌注损伤的肾功能。
J Cell Mol Med. 2021 Aug;25(16):7675-7689. doi: 10.1111/jcmm.16613. Epub 2021 Jun 23.
5
Prion Protein Overexpression in Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Effectively Protected Rodent Kidney Against Ischemia-Reperfusion Injury Via Enhancing ATP/Mitochondrial Biogenesis-Role of ADMSC Rejuvenation and Proliferation.脂肪间充质干细胞（ADMSCs）中朊病毒蛋白的过表达通过增强 ATP/线粒体生物发生有效地保护了啮齿动物肾脏免受缺血再灌注损伤-ADMSC 年轻化和增殖的作用。
Cell Transplant. 2023 Jan-Dec;32:9636897231211067. doi: 10.1177/09636897231211067.
6
Xenogeneic and Allogeneic Mesenchymal Stem Cells Effectively Protect the Lung Against Ischemia-reperfusion Injury Through Downregulating the Inflammatory, Oxidative Stress, and Autophagic Signaling Pathways in Rat.异种和同种异体间充质干细胞通过下调大鼠肺缺血再灌注损伤中的炎症、氧化应激和自噬信号通路而有效保护肺。
Cell Transplant. 2020 Jan-Dec;29:963689720954140. doi: 10.1177/0963689720954140.
7
Additional benefit of induced pluripotent stem cell-derived mesenchymal stem cell therapy on sepsis syndrome-associated acute kidney injury in rat treated with antibiotic. 抗生素治疗脓毒症综合征相关急性肾损伤大鼠中诱导多能干细胞衍生的间充质干细胞治疗的额外益处。
Stem Cell Res Ther. 2021 Oct 7;12(1):526. doi: 10.1186/s13287-021-02582-5.
8
Extracorporeal Shock Wave Enhanced Exogenous Mitochondria into Adipose-Derived Mesenchymal Stem Cells and Further Preserved Heart Function in Rat Dilated Cardiomyopathy.体外冲击波增强外源性线粒体进入脂肪来源间充质干细胞并进一步保护大鼠扩张型心肌病的心功能。
Biomedicines. 2021 Sep 30;9(10):1362. doi: 10.3390/biomedicines9101362.
9
Combined therapy with dapagliflozin and entresto offers an additional benefit on improving the heart function in rat after ischemia-reperfusion injury.达格列净联合恩格列净治疗可改善缺血再灌注损伤后大鼠心功能。
Biomed J. 2023 Jun;46(3):100546. doi: 10.1016/j.bj.2022.06.002. Epub 2022 Jun 16.
10
Entresto protected the cardiomyocytes and preserved heart function in cardiorenal syndrome rat fed with high-protein diet through regulating the oxidative stress and Mfn2-mediated mitochondrial functional integrity.恩格列净通过调节氧化应激和 Mfn2 介导的线粒体功能完整性，保护了高蛋白饮食喂养的心血肾综合征大鼠的心肌细胞并维持了心脏功能。
Biomed Pharmacother. 2021 Dec;144:112244. doi: 10.1016/j.biopha.2021.112244. Epub 2021 Oct 1.

引用本文的文献

1
Nanog overexpression enhances the therapeutic efficacy of ADMSCs in AMI rats via the upregulation of JAK/STAT3 signaling and cyclin-mitochondrial expression.Nanog过表达通过上调JAK/STAT3信号通路和细胞周期蛋白-线粒体表达增强了脂肪间充质干细胞对急性心肌梗死大鼠的治疗效果。
Int J Biol Sci. 2025 Jul 4;21(10):4450-4466. doi: 10.7150/ijbs.112824. eCollection 2025.
2
Human umbilical cord-derived mesenchymal stromal cells improve myocardial fibrosis and restore miRNA-133a expression in diabetic cardiomyopathy.人脐带间充质基质细胞可改善糖尿病心肌病中的心肌纤维化并恢复miRNA-133a表达。
Stem Cell Res Ther. 2024 Apr 24;15(1):120. doi: 10.1186/s13287-024-03715-2.
3

本文引用的文献

1
Overexpression of miR-19a and miR-20a in iPS-MSCs preserves renal function of chronic kidney disease with acute ischaemia-reperfusion injury in rat.miR-19a 和 miR-20a 在 iPS-MSCs 中的过表达可保护大鼠慢性肾脏病伴急性缺血再灌注损伤的肾功能。
J Cell Mol Med. 2021 Aug;25(16):7675-7689. doi: 10.1111/jcmm.16613. Epub 2021 Jun 23.
2
Early intramyocardial implantation of exogenous mitochondria effectively preserved left ventricular function in doxorubicin-induced dilated cardiomyopathy rat.早期心肌内植入外源性线粒体可有效保护阿霉素诱导的扩张型心肌病大鼠的左心室功能。
Am J Transl Res. 2020 Aug 15;12(8):4612-4627. eCollection 2020.
3
Toll-like receptors in cardiac hypertrophy.
心脏肥大中的Toll样受体
Front Cardiovasc Med. 2023 Apr 11;10:1143583. doi: 10.3389/fcvm.2023.1143583. eCollection 2023.
4
The Role of MicroRNAs in Dilated Cardiomyopathy: New Insights for an Old Entity.微小 RNA 在扩张型心肌病中的作用：旧实体的新见解。
Int J Mol Sci. 2022 Nov 5;23(21):13573. doi: 10.3390/ijms232113573.
5
Mesenchymal Stem Cell Immunomodulation: A Novel Intervention Mechanism in Cardiovascular Disease.间充质干细胞免疫调节：心血管疾病中的一种新型干预机制
Front Cell Dev Biol. 2022 Jan 12;9:742088. doi: 10.3389/fcell.2021.742088. eCollection 2021.
6
miR-20a Overexpression in Adipose-Derived Mesenchymal Stem Cells Promotes Therapeutic Efficacy in Murine Lupus Nephritis by Regulating Autophagy.脂肪来源间充质干细胞中miR-20a的过表达通过调节自噬促进小鼠狼疮性肾炎的治疗效果。
Stem Cells Int. 2021 Oct 21;2021:3746335. doi: 10.1155/2021/3746335. eCollection 2021.
Human Umbilical Cord-Derived Mesenchymal Stem Cells for Acute Respiratory Distress Syndrome.
人脐带间充质干细胞治疗急性呼吸窘迫综合征。
Crit Care Med. 2020 May;48(5):e391-e399. doi: 10.1097/CCM.0000000000004285.
4
Sacubitril/Valsartan in Asian Patients with Heart Failure with Reduced Ejection Fraction.沙库巴曲缬沙坦用于亚洲射血分数降低的心力衰竭患者
Korean Circ J. 2019 Jun;49(6):469-484. doi: 10.4070/kcj.2019.0136.
5
Outcomes and Effect of Treatment According to Etiology in HFrEF: An Analysis of PARADIGM-HF.射血分数降低心衰（HFrEF）患者按病因的治疗结局和效果：PARADIGM-HF 分析。
JACC Heart Fail. 2019 Jun;7(6):457-465. doi: 10.1016/j.jchf.2019.02.015. Epub 2019 May 8.
6
Inducible pluripotent stem cell-derived mesenchymal stem cell therapy effectively protected kidney from acute ischemia-reperfusion injury.诱导多能干细胞衍生的间充质干细胞疗法有效保护肾脏免受急性缺血再灌注损伤。
Am J Transl Res. 2018 Oct 15;10(10):3053-3067. eCollection 2018.
7
Early administration of empagliflozin preserved heart function in cardiorenal syndrome in rat.恩格列净早期给药可改善大鼠心肝综合征中心功能。
Biomed Pharmacother. 2019 Jan;109:658-670. doi: 10.1016/j.biopha.2018.10.095. Epub 2018 Nov 4.
8
Mesenchymal Stem Cells (MSC) Derived from Induced Pluripotent Stem Cells (iPSC) Equivalent to Adipose-Derived MSC in Promoting Intestinal Healing and Microbiome Normalization in Mouse Inflammatory Bowel Disease Model.诱导多能干细胞（iPSC）衍生的间充质干细胞（MSC）在促进小鼠炎症性肠病模型的肠道愈合和微生物组正常化方面与脂肪来源的 MSC 相当。
Stem Cells Transl Med. 2018 Jun;7(6):456-467. doi: 10.1002/sctm.17-0305. Epub 2018 Apr 10.
9
Immunosuppressive Mesenchymal Stromal Cells Derived from Human-Induced Pluripotent Stem Cells Induce Human Regulatory T Cells and .源自人诱导多能干细胞的免疫抑制性间充质基质细胞诱导人调节性T细胞以及……（原文此处不完整）
Front Immunol. 2018 Jan 25;8:1991. doi: 10.3389/fimmu.2017.01991. eCollection 2017.
10
Human induced pluripotent stem cell-derived mesenchymal stem cells prevent adriamycin nephropathy in mice.人诱导多能干细胞来源的间充质干细胞可预防小鼠阿霉素肾病。
Oncotarget. 2017 Oct 10;8(61):103640-103656. doi: 10.18632/oncotarget.21760. eCollection 2017 Nov 28.