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Induced pluripotent stem cells can improve thrombolytic effect of low-dose rt-PA after acute carotid thrombosis in rat
- Source :
- Stem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-16 (2021), Stem Cell Research & Therapy
- Publication Year :
- 2021
- Publisher :
- BMC, 2021.
-
Abstract
- Background Intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) is the standard treatment for acute ischemic stroke. Standard-dose rt-PA (0.9 mg/kg) is known to achieve good recanalization but carries a high bleeding risk. Lower dose of rt-PA has less bleeding risk but carries a high re-occlusion rate. We investigate if induced pluripotent stem cells (iPSCs) can improve the thrombolytic effect of low-dose rt-PA (0.45 mg/kg). Methods Single irradiation with 6 mW/cm2 light-emitting diode (LED) for 4 h at rat common carotid artery was used as thrombosis model according to our previous report. Endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1), and interleukin 1 beta (IL-1 beta) were used as the inflammatory markers for artery endothelial injury. Angiopoietin-2 (AP-2), brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were examined in artery wall and iPSCs culture. Animal ultrasound was used to evaluate the stenosis degree of common carotid artery before and at 2 h, 24 h, 4 days and 7 days after LED irradiation. Results After LED irradiation alone, there was a persistent occlusion from 2 h to 7 days. Standard-dose rt-PA alone could recanalize the occluded artery from 24 h to 7 days to stenotic degree ≤ 50%. Low-dose rt-PA or 1 × 106 mouse iPSCs alone could not recanalize the occluded arteries from 2 h to 7 days. Combination use of low-dose rt-PA plus 1 × 106 mouse iPSCs caused better recanalization from 24 h to 7 days. ET-1, ICAM-1 and IL-1 beta were strongly expressed after LED irradiation but reduced after iPSCs treatment. AP-2, BDNF and VEGF were rarely induced after LED irradiation but strongly expressed after iPSCs treatment. In vitro study showed iPSCs could express AP-2, BDNF and VEGF. Conclusion The adjuvant use of iPSCs may help improving the thrombolytic effect of low-dose rt-PA by suppressing inflammatory factors and inducing angiogenic trophic factors. Stem cells could be a potential regimen in acute thrombolytic therapy to improve recanalization and reduce complications.
- Subjects :
- Vascular Endothelial Growth Factor A
Medicine (General)
Endothelium
medicine.medical_treatment
Induced Pluripotent Stem Cells
Medicine (miscellaneous)
QD415-436
Pharmacology
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Tissue plasminogen activator
Biochemistry
Brain Ischemia
chemistry.chemical_compound
Mice
R5-920
Carotid thrombosis
medicine.artery
medicine
Animals
Common carotid artery
Carotid Artery Thrombosis
Stem cell
business.industry
Research
Cell Biology
Thrombolysis
medicine.disease
Thrombosis
Rats
Vascular endothelial growth factor
Stroke
medicine.anatomical_structure
chemistry
Molecular Medicine
business
Artery
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 17576512
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Stem Cell Research & Therapy
- Accession number :
- edsair.doi.dedup.....1e4433a420df593853ed94ff5d50f885