Intravenous Injection of Clinical Grade Human MSCs after Experimental Stroke: Functional Benefit and Microvascular Effect
Stroke is the leading cause of disability in adults. Many current clinical trials use intravenous (IV) administration of human bone marrow-derived mesenchymal stem cells (BM-MSCs). This autologous graft requires a delay for ex vivo expansion of cells. We followed microvascular effects and mechanisms...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2016-12-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368916X691132 |
| _version_ | 1831693514165977088 |
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| author | Anaïck Moisan Isabelle Favre Claire Rome Florence De Fraipont Emmanuelle Grillon Nicolas Coquery Hervé Mathieu Virginie Mayan Bernadette Naegele Marc Hommel Marie-Jeanne Richard Emmanuel Luc Barbier Chantal Remy Olivier Detante |
| author_facet | Anaïck Moisan Isabelle Favre Claire Rome Florence De Fraipont Emmanuelle Grillon Nicolas Coquery Hervé Mathieu Virginie Mayan Bernadette Naegele Marc Hommel Marie-Jeanne Richard Emmanuel Luc Barbier Chantal Remy Olivier Detante |
| author_sort | Anaïck Moisan |
| collection | DOAJ |
| description | Stroke is the leading cause of disability in adults. Many current clinical trials use intravenous (IV) administration of human bone marrow-derived mesenchymal stem cells (BM-MSCs). This autologous graft requires a delay for ex vivo expansion of cells. We followed microvascular effects and mechanisms of action involved after an IV injection of human BM-MSCs (hBM-MSCs) at a subacute phase of stroke. Rats underwent a transient middle cerebral artery occlusion (MCAo) or a surgery without occlusion (sham) at day 0 (D0). At D8, rats received an IV injection of 3 million hBM-MSCs or PBS-glutamine. In a longitudinal behavioral follow-up, we showed delayed somatosensory and cognitive benefits 4 to 7 weeks after hBM-MSC injection. In a separate longitudinal in vivo magnetic resonance imaging (MRI) study, we observed an enhanced vascular density in the ischemic area 2 and 3 weeks after hBM-MSC injection. Histology and quantitative polymerase chain reaction (qPCR) revealed an overexpression of angiogenic factors such as Ang1 and transforming growth factor-β1 (TGF-β1) at D16 in hBM-MSC-treated MCAo rats compared to PBS-treated MCAo rats. Altogether, delayed IV injection of hBM-MSCs provides functional benefits and increases cerebral angiogenesis in the stroke lesion via a release of endogenous angiogenic factors enhancing the stabilization of newborn vessels. Enhanced angiogenesis could therefore be a means of improving functional recovery after stroke. |
| first_indexed | 2024-12-20T12:14:59Z |
| format | Article |
| id | doaj.art-6e270f63311e41ed9dacf79afbc76e9b |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-20T12:14:59Z |
| publishDate | 2016-12-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-6e270f63311e41ed9dacf79afbc76e9b2022-12-21T19:41:09ZengSAGE PublishingCell Transplantation0963-68971555-38922016-12-012510.3727/096368916X691132Intravenous Injection of Clinical Grade Human MSCs after Experimental Stroke: Functional Benefit and Microvascular EffectAnaïck Moisan0Isabelle Favre1Claire Rome2Florence De Fraipont3Emmanuelle Grillon4Nicolas Coquery5Hervé Mathieu6Virginie Mayan7Bernadette Naegele8Marc Hommel9Marie-Jeanne Richard10Emmanuel Luc Barbier11Chantal Remy12Olivier Detante13French Blood Company/CHU de Grenoble, Hôpital Michallon, Unité de Thérapie et d'Ingénierie Cellulaire, Saint Ismier, FranceUnité Neurovasculaire, Département de Neurologie, Hôpital Michallon, CHU Grenoble Alpes, Grenoble, FranceUniversité Grenoble Alpes, Grenoble, FranceInstitut Albert Bonniot, Inserm, Université Grenoble Alpes, Grenoble, FranceUniversité Grenoble Alpes, Grenoble, FranceUniversité Grenoble Alpes, Grenoble, FranceUniversité Grenoble Alpes, Grenoble, FranceUniversité Grenoble Alpes, Grenoble, FranceUnité Neurovasculaire, Département de Neurologie, Hôpital Michallon, CHU Grenoble Alpes, Grenoble, FranceDépartement de Recherche Clinique, Hôpital Michallon, CHU de Grenoble, Grenoble, FranceInstitut Albert Bonniot, Inserm, Université Grenoble Alpes, Grenoble, FranceUniversité Grenoble Alpes, Grenoble, FranceUniversité Grenoble Alpes, Grenoble, FranceUnité Neurovasculaire, Département de Neurologie, Hôpital Michallon, CHU Grenoble Alpes, Grenoble, FranceStroke is the leading cause of disability in adults. Many current clinical trials use intravenous (IV) administration of human bone marrow-derived mesenchymal stem cells (BM-MSCs). This autologous graft requires a delay for ex vivo expansion of cells. We followed microvascular effects and mechanisms of action involved after an IV injection of human BM-MSCs (hBM-MSCs) at a subacute phase of stroke. Rats underwent a transient middle cerebral artery occlusion (MCAo) or a surgery without occlusion (sham) at day 0 (D0). At D8, rats received an IV injection of 3 million hBM-MSCs or PBS-glutamine. In a longitudinal behavioral follow-up, we showed delayed somatosensory and cognitive benefits 4 to 7 weeks after hBM-MSC injection. In a separate longitudinal in vivo magnetic resonance imaging (MRI) study, we observed an enhanced vascular density in the ischemic area 2 and 3 weeks after hBM-MSC injection. Histology and quantitative polymerase chain reaction (qPCR) revealed an overexpression of angiogenic factors such as Ang1 and transforming growth factor-β1 (TGF-β1) at D16 in hBM-MSC-treated MCAo rats compared to PBS-treated MCAo rats. Altogether, delayed IV injection of hBM-MSCs provides functional benefits and increases cerebral angiogenesis in the stroke lesion via a release of endogenous angiogenic factors enhancing the stabilization of newborn vessels. Enhanced angiogenesis could therefore be a means of improving functional recovery after stroke.https://doi.org/10.3727/096368916X691132 |
| spellingShingle | Anaïck Moisan Isabelle Favre Claire Rome Florence De Fraipont Emmanuelle Grillon Nicolas Coquery Hervé Mathieu Virginie Mayan Bernadette Naegele Marc Hommel Marie-Jeanne Richard Emmanuel Luc Barbier Chantal Remy Olivier Detante Intravenous Injection of Clinical Grade Human MSCs after Experimental Stroke: Functional Benefit and Microvascular Effect Cell Transplantation |
| title | Intravenous Injection of Clinical Grade Human MSCs after Experimental Stroke: Functional Benefit and Microvascular Effect |
| title_full | Intravenous Injection of Clinical Grade Human MSCs after Experimental Stroke: Functional Benefit and Microvascular Effect |
| title_fullStr | Intravenous Injection of Clinical Grade Human MSCs after Experimental Stroke: Functional Benefit and Microvascular Effect |
| title_full_unstemmed | Intravenous Injection of Clinical Grade Human MSCs after Experimental Stroke: Functional Benefit and Microvascular Effect |
| title_short | Intravenous Injection of Clinical Grade Human MSCs after Experimental Stroke: Functional Benefit and Microvascular Effect |
| title_sort | intravenous injection of clinical grade human mscs after experimental stroke functional benefit and microvascular effect |
| url | https://doi.org/10.3727/096368916X691132 |
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