Therapeutic efficacy of intra-arterial administration of induced pluripotent stem cells-derived neural progenitor cells in acute experimental ischemic stroke in rats
Aim. Neural progenitor cells (NPC) are used for the development of cell therapies of neurological diseases. Their stereotaxic transplantation in the middle cerebral artery occlusion (MCAO) model imitating ischemic stroke results in symptom aleviation. However, exploration of less invasive transplant...
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Language: | Russian |
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Federal Research Center of Transplantology and Artificial Organs named after V.I.Shumakov
2019-05-01
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Series: | Vestnik Transplantologii i Iskusstvennyh Organov |
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Online Access: | https://journal.transpl.ru/vtio/article/view/1001 |
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doaj-7c718b2681274f22840ceec0d1496570 |
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record_format |
Article |
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DOAJ |
language |
Russian |
format |
Article |
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DOAJ |
author |
D. D. Namestnikova I. L. Gubskiy D. I. Salikhova G. E. Leonov K. K. Sukhinich P. A. Melnikov D. A. Vishnevskiy E. A. Cherkashova A. N. Gabashvili T. B. Bukharova V. V. Burunova T. Kh. Fatkhudinov V. P. Chekhonin L. V. Gubsky S. L. Kiselev D. V. Goldstein K. N. Yarygin |
spellingShingle |
D. D. Namestnikova I. L. Gubskiy D. I. Salikhova G. E. Leonov K. K. Sukhinich P. A. Melnikov D. A. Vishnevskiy E. A. Cherkashova A. N. Gabashvili T. B. Bukharova V. V. Burunova T. Kh. Fatkhudinov V. P. Chekhonin L. V. Gubsky S. L. Kiselev D. V. Goldstein K. N. Yarygin Therapeutic efficacy of intra-arterial administration of induced pluripotent stem cells-derived neural progenitor cells in acute experimental ischemic stroke in rats Vestnik Transplantologii i Iskusstvennyh Organov neural progenitor cells induced pluripotent stem cells cell therapy ischemic stroke middle cerebral artery occlusion model |
author_facet |
D. D. Namestnikova I. L. Gubskiy D. I. Salikhova G. E. Leonov K. K. Sukhinich P. A. Melnikov D. A. Vishnevskiy E. A. Cherkashova A. N. Gabashvili T. B. Bukharova V. V. Burunova T. Kh. Fatkhudinov V. P. Chekhonin L. V. Gubsky S. L. Kiselev D. V. Goldstein K. N. Yarygin |
author_sort |
D. D. Namestnikova |
title |
Therapeutic efficacy of intra-arterial administration of induced pluripotent stem cells-derived neural progenitor cells in acute experimental ischemic stroke in rats |
title_short |
Therapeutic efficacy of intra-arterial administration of induced pluripotent stem cells-derived neural progenitor cells in acute experimental ischemic stroke in rats |
title_full |
Therapeutic efficacy of intra-arterial administration of induced pluripotent stem cells-derived neural progenitor cells in acute experimental ischemic stroke in rats |
title_fullStr |
Therapeutic efficacy of intra-arterial administration of induced pluripotent stem cells-derived neural progenitor cells in acute experimental ischemic stroke in rats |
title_full_unstemmed |
Therapeutic efficacy of intra-arterial administration of induced pluripotent stem cells-derived neural progenitor cells in acute experimental ischemic stroke in rats |
title_sort |
therapeutic efficacy of intra-arterial administration of induced pluripotent stem cells-derived neural progenitor cells in acute experimental ischemic stroke in rats |
publisher |
Federal Research Center of Transplantology and Artificial Organs named after V.I.Shumakov |
series |
Vestnik Transplantologii i Iskusstvennyh Organov |
issn |
1995-1191 |
publishDate |
2019-05-01 |
description |
Aim. Neural progenitor cells (NPC) are used for the development of cell therapies of neurological diseases. Their stereotaxic transplantation in the middle cerebral artery occlusion (MCAO) model imitating ischemic stroke results in symptom aleviation. However, exploration of less invasive transplantation options is essential, because stereotaxic transplantation is a complex procedure and can be applied to humans only by vital indications in a specialized neurological ward. The aim of the present study was to evaluate the efficacy of cell therapy of the experimental ischemic stroke by the intra-arterial transplantation of NPC.Materials and methods. NPC for transplantation (IPSC-NPC) were derived by two-stage differentiation of cells of a stable line of human induced pluripotent stem cells. Stroke modeling in rats was carried out by transitory 90 min endovascular MCAO by a silicon-tipped filament. NPC were transplanted 24 hours after MCAO. Repetitive magnetic resonance tomography of experimental animals was made with the Bruker BioSpin ClinScan tomograph with 7 Tl magnetic field induction. Animal survival rate and neurological deficit (using mNSS standard stroke severity scale) were evaluated at the 1st (before IPSC-NPC transplantation), 7th and 14th day after transplantation. Histological studies were carried out following standard protocols.Results. Intra-arterial transplantation of 7 × 105 IPSC-NPC in 1 ml at a constant 100 l/min rate in case of secured blood flow through the internal carotid artery did not cause brain capillary embolism, additional cytotoxic brain tissue edemas or other complications, while inducing increase of animal survival rate and enhanced revert of the neurological deficit. IPSC-NPC accumulation in brain after intra-arterial infusion was demonstrated. Some cells interacted with the capillary endothelium and probably penetrated through the blood-brain barrier.Conclusion. Therapeutic efficacy of the systemic, intra-arterial administration of NPC in ischemic stroke has been experimentally proven. A method of secure intra-arterial infusion of cell material into the internal carotid artery middle in rats has been developed and tested. |
topic |
neural progenitor cells induced pluripotent stem cells cell therapy ischemic stroke middle cerebral artery occlusion model |
url |
https://journal.transpl.ru/vtio/article/view/1001 |
work_keys_str_mv |
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doaj-7c718b2681274f22840ceec0d14965702021-07-29T09:08:34ZrusFederal Research Center of Transplantology and Artificial Organs named after V.I.Shumakov Vestnik Transplantologii i Iskusstvennyh Organov1995-11912019-05-0121115316410.15825/1995-1191-2019-1-153-164771Therapeutic efficacy of intra-arterial administration of induced pluripotent stem cells-derived neural progenitor cells in acute experimental ischemic stroke in ratsD. D. Namestnikova0I. L. Gubskiy1D. I. Salikhova2G. E. Leonov3K. K. Sukhinich4P. A. Melnikov5D. A. Vishnevskiy6E. A. Cherkashova7A. N. Gabashvili8T. B. Bukharova9V. V. Burunova10T. Kh. Fatkhudinov11V. P. Chekhonin12L. V. Gubsky13S. L. Kiselev14D. V. Goldstein15K. N. Yarygin16Pirogov Russian National Research Medical University; Federal center of cerebrovascular pathology and stroke, Ministry of Health care of Russian FederationFederal center of cerebrovascular pathology and stroke, Ministry of Health care of Russian FederationResearch Centre of Medical GeneticsResearch Centre of Medical GeneticsKoltzov Institute of Developmental BiologySerbsky Federal Medical Research Centre of Psychiatry and NarcologyPirogov Russian National Research Medical UniversityFederal center of cerebrovascular pathology and stroke, Ministry of Health care of Russian FederationInstitute of Biomedical Chemistry; Vavilov Institute of General GeneticsResearch Centre of Medical GeneticsInstitute of Biomedical ChemistryResearch Centre of Medical GeneticsPirogov Russian National Research Medical University; Serbsky Federal Medical Research Centre of Psychiatry and NarcologyPirogov Russian National Research Medical University; Federal center of cerebrovascular pathology and stroke, Ministry of Health care of Russian FederationVavilov Institute of General Genetics; Research Centre of Medical GeneticsResearch Centre of Medical GeneticsInstitute of Biomedical ChemistryAim. Neural progenitor cells (NPC) are used for the development of cell therapies of neurological diseases. Their stereotaxic transplantation in the middle cerebral artery occlusion (MCAO) model imitating ischemic stroke results in symptom aleviation. However, exploration of less invasive transplantation options is essential, because stereotaxic transplantation is a complex procedure and can be applied to humans only by vital indications in a specialized neurological ward. The aim of the present study was to evaluate the efficacy of cell therapy of the experimental ischemic stroke by the intra-arterial transplantation of NPC.Materials and methods. NPC for transplantation (IPSC-NPC) were derived by two-stage differentiation of cells of a stable line of human induced pluripotent stem cells. Stroke modeling in rats was carried out by transitory 90 min endovascular MCAO by a silicon-tipped filament. NPC were transplanted 24 hours after MCAO. Repetitive magnetic resonance tomography of experimental animals was made with the Bruker BioSpin ClinScan tomograph with 7 Tl magnetic field induction. Animal survival rate and neurological deficit (using mNSS standard stroke severity scale) were evaluated at the 1st (before IPSC-NPC transplantation), 7th and 14th day after transplantation. Histological studies were carried out following standard protocols.Results. Intra-arterial transplantation of 7 × 105 IPSC-NPC in 1 ml at a constant 100 l/min rate in case of secured blood flow through the internal carotid artery did not cause brain capillary embolism, additional cytotoxic brain tissue edemas or other complications, while inducing increase of animal survival rate and enhanced revert of the neurological deficit. IPSC-NPC accumulation in brain after intra-arterial infusion was demonstrated. Some cells interacted with the capillary endothelium and probably penetrated through the blood-brain barrier.Conclusion. Therapeutic efficacy of the systemic, intra-arterial administration of NPC in ischemic stroke has been experimentally proven. A method of secure intra-arterial infusion of cell material into the internal carotid artery middle in rats has been developed and tested.https://journal.transpl.ru/vtio/article/view/1001neural progenitor cellsinduced pluripotent stem cellscell therapyischemic strokemiddle cerebral artery occlusion model |