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药物对经静脉移植犬脂肪组织来源间充质干细胞的小鼠肺血栓栓塞症的影响。

Medication effects on pulmonary thromboembolism in mice intravenously transplanted with canine adipose tissue-derived mesenchymal stem cells.

机构信息

Department of Veterinary Surgery, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.

Department of Veterinary Obstetrics and Theriogenology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.

出版信息

J Vet Sci. 2024 Nov;25(6):e80. doi: 10.4142/jvs.24163.

DOI:10.4142/jvs.24163
PMID:39608774
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11611486/
Abstract

IMPORTANCE

The intravenous administration of adipose tissue-derived mesenchymal stem cells (AdMSCs) in veterinary medicine is a promising regenerative therapy, but it can lead to severe complications, including pulmonary thromboembolism (PTE).

OBJECTIVE

As part of an ongoing study, this study examined the impact of medications, such as heparin, aspirin, and sodium nitroprusside (SNP), on the factors linked to PTE after an intravenous injection of canine mesenchymal stem cell into experimental animals.

METHODS

Fluorescently labeled canine AdMSCs were administered intravenously into the tail veins of five-week-old male BALB/c hairless mice. This study compared the survival rates, biodistribution, platelet counts, D-dimer levels, and histological examination results among the drug treatment experimental and the control groups.

RESULTS

The final survival rates in the SNP, control aspirin, and heparin groups were 25%, 33%, 50%, and 100%, respectively. imaging confirmed fluorescence exclusively in the lungs of all subjects who died during the injection, with no fluorescence detected in the other organs. On the other hand, in the heparin experimental group, the surviving individuals exhibited fluorescence in the lungs and the liver on day one. Histological biopsies revealed PTE in all deceased individuals within the medication experimental groups ( = 0.029).

CONCLUSIONS AND RELEVANCE

Heparin was highly effective, with no PTE-related deaths observed when used alongside cell injections. Aspirin revealed moderate effectiveness, surpassing the control group. On the other hand, the efficacy of SNP was inferior to that of the other two drugs.

摘要

重要性

在兽医医学中,静脉内给予脂肪组织源性间充质干细胞(AdMSCs)是一种很有前途的再生治疗方法,但它会导致严重的并发症,包括肺血栓栓塞症(PTE)。

目的

作为正在进行的研究的一部分,本研究检查了肝素、阿司匹林和硝普钠(SNP)等药物对静脉内注射犬间充质干细胞后与 PTE 相关的因素的影响。

方法

将荧光标记的犬 AdMSCs 静脉内注射到 5 周龄雄性 BALB/c 无毛小鼠的尾静脉中。本研究比较了药物治疗实验组和对照组的存活率、生物分布、血小板计数、D-二聚体水平和组织学检查结果。

结果

SNP、对照阿司匹林和肝素组的最终存活率分别为 25%、33%、50%和 100%。成像确认了所有在注射过程中死亡的动物的肺部仅存在荧光,而其他器官均未检测到荧光。另一方面,在肝素实验组中,存活的个体在注射后第一天肺部和肝脏均显示荧光。组织学活检显示在药物实验组的所有死亡个体中均存在 PTE( = 0.029)。

结论和相关性

肝素与细胞注射一起使用时非常有效,没有观察到与 PTE 相关的死亡。阿司匹林显示出中等疗效,超过了对照组。另一方面,SNP 的疗效不如其他两种药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/038f/11611486/12d5ead0422c/jvs-25-e80-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/038f/11611486/b46a49426f40/jvs-25-e80-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/038f/11611486/e9b360db16d7/jvs-25-e80-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/038f/11611486/62f934095bd2/jvs-25-e80-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/038f/11611486/708887d67010/jvs-25-e80-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/038f/11611486/12d5ead0422c/jvs-25-e80-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/038f/11611486/b46a49426f40/jvs-25-e80-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/038f/11611486/e9b360db16d7/jvs-25-e80-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/038f/11611486/62f934095bd2/jvs-25-e80-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/038f/11611486/708887d67010/jvs-25-e80-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/038f/11611486/12d5ead0422c/jvs-25-e80-g005.jpg

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本文引用的文献

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2
Improved MSC Minimal Criteria to Maximize Patient Safety: A Call to Embrace Tissue Factor and Hemocompatibility Assessment of MSC Products.改良 MSC 最小标准以最大化患者安全:呼吁采用组织因子和 MSC 产品血液相容性评估。
Stem Cells Transl Med. 2022 Mar 3;11(1):2-13. doi: 10.1093/stcltm/szab005.
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Thrombogenic Risk Induced by Intravascular Mesenchymal Stem Cell Therapy: Current Status and Future Perspectives.
血管内间充质干细胞治疗引起的血栓形成风险:现状与未来展望。
Cells. 2019 Sep 27;8(10):1160. doi: 10.3390/cells8101160.
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Aspirin blocks formation of metastatic intravascular niches by inhibiting platelet-derived COX-1/thromboxane A2.阿司匹林通过抑制血小板衍生的 COX-1/血栓素 A2 来阻断转移性血管内龛的形成。
J Clin Invest. 2019 Mar 25;129(5):1845-1862. doi: 10.1172/JCI121985.
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A Systematic Review on the Use of Aspirin in the Prevention of Deep Vein Thrombosis in Major Elective Lower Limb Orthopedic Surgery: An Update from the Past 3 Years.阿司匹林在择期下肢大关节骨科手术中预防深静脉血栓形成应用的系统评价:过去3年的最新进展
Surg J (N Y). 2017 Dec 29;3(4):e191-e196. doi: 10.1055/s-0037-1615817. eCollection 2017 Oct.
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