Induced pluripotent stem cells can improve thrombolytic effect of low-dose rt-PA after acute carotid thrombosis in rat
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 ris...
| Hoofdauteurs: | , , , , , , |
|---|---|
| Formaat: | Artikel |
| Taal: | English |
| Gepubliceerd in: |
BMC
2021-10-01
|
| Reeks: | Stem Cell Research & Therapy |
| Onderwerpen: | |
| Online toegang: | https://doi.org/10.1186/s13287-021-02615-z |
| _version_ | 1830284163237806080 |
|---|---|
| author | Hsi-Lung Hsieh Ching-Chung Liang Cheng-You Lu Jen-Tsung Yang Chiu-Yen Chung Yu-Shien Ko Tsong-Hai Lee |
| author_facet | Hsi-Lung Hsieh Ching-Chung Liang Cheng-You Lu Jen-Tsung Yang Chiu-Yen Chung Yu-Shien Ko Tsong-Hai Lee |
| author_sort | Hsi-Lung Hsieh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T03:14:34Z |
| format | Article |
| id | doaj.art-7cc3d14182a44c89a0e98c48a0d6a439 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-19T03:14:34Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-7cc3d14182a44c89a0e98c48a0d6a4392022-12-21T20:37:56ZengBMCStem Cell Research & Therapy1757-65122021-10-0112111610.1186/s13287-021-02615-zInduced pluripotent stem cells can improve thrombolytic effect of low-dose rt-PA after acute carotid thrombosis in ratHsi-Lung Hsieh0Ching-Chung Liang1Cheng-You Lu2Jen-Tsung Yang3Chiu-Yen Chung4Yu-Shien Ko5Tsong-Hai Lee6Department of Nursing, Division of Basic Medical Sciences, Research Center for Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology, Chang Gung University of Science and TechnologyFemale Urology Section, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, and College of Medicine, Chang Gung UniversityCardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationDepartment of Neurosurgery, Chia-Yi Chang Gung Memorial Hospital, Chia-Yi, Taiwan, and College of Medicine, Chang Gung UniversityDepartment of Neurosurgery, Chia-Yi Chang Gung Memorial Hospital, Chia-Yi, Taiwan, and College of Medicine, Chang Gung UniversityThe First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, and College of Medicine, Chang Gung UniversityStroke Center and Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, and College of Medicine, Chang Gung UniversityAbstract 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.https://doi.org/10.1186/s13287-021-02615-zCarotid thrombosisEndotheliumStem cellThrombolysisTissue plasminogen activator |
| spellingShingle | Hsi-Lung Hsieh Ching-Chung Liang Cheng-You Lu Jen-Tsung Yang Chiu-Yen Chung Yu-Shien Ko Tsong-Hai Lee Induced pluripotent stem cells can improve thrombolytic effect of low-dose rt-PA after acute carotid thrombosis in rat Stem Cell Research & Therapy Carotid thrombosis Endothelium Stem cell Thrombolysis Tissue plasminogen activator |
| title | Induced pluripotent stem cells can improve thrombolytic effect of low-dose rt-PA after acute carotid thrombosis in rat |
| title_full | Induced pluripotent stem cells can improve thrombolytic effect of low-dose rt-PA after acute carotid thrombosis in rat |
| title_fullStr | Induced pluripotent stem cells can improve thrombolytic effect of low-dose rt-PA after acute carotid thrombosis in rat |
| title_full_unstemmed | Induced pluripotent stem cells can improve thrombolytic effect of low-dose rt-PA after acute carotid thrombosis in rat |
| title_short | Induced pluripotent stem cells can improve thrombolytic effect of low-dose rt-PA after acute carotid thrombosis in rat |
| title_sort | induced pluripotent stem cells can improve thrombolytic effect of low dose rt pa after acute carotid thrombosis in rat |
| topic | Carotid thrombosis Endothelium Stem cell Thrombolysis Tissue plasminogen activator |
| url | https://doi.org/10.1186/s13287-021-02615-z |
| work_keys_str_mv | AT hsilunghsieh inducedpluripotentstemcellscanimprovethrombolyticeffectoflowdosertpaafteracutecarotidthrombosisinrat AT chingchungliang inducedpluripotentstemcellscanimprovethrombolyticeffectoflowdosertpaafteracutecarotidthrombosisinrat AT chengyoulu inducedpluripotentstemcellscanimprovethrombolyticeffectoflowdosertpaafteracutecarotidthrombosisinrat AT jentsungyang inducedpluripotentstemcellscanimprovethrombolyticeffectoflowdosertpaafteracutecarotidthrombosisinrat AT chiuyenchung inducedpluripotentstemcellscanimprovethrombolyticeffectoflowdosertpaafteracutecarotidthrombosisinrat AT yushienko inducedpluripotentstemcellscanimprovethrombolyticeffectoflowdosertpaafteracutecarotidthrombosisinrat AT tsonghailee inducedpluripotentstemcellscanimprovethrombolyticeffectoflowdosertpaafteracutecarotidthrombosisinrat |