Effects of mesenchymal stem cell therapy, in association with pharmacologically active microcarriers releasing VEGF, in an ischaemic stroke model in the rat
[Display omitted] Few effective therapeutic interventions are available to limit brain damage and functional deficits after ischaemic stroke. Within this context, mesenchymal stem cell (MSC) therapy carries minimal risks while remaining efficacious through the secretion of trophic, protective, neuro...
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| Veröffentlicht in: | Acta biomaterialia 2015-03, Vol.15 (15), p.77-88 |
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| creator | Quittet, Marie-Sophie Touzani, Omar Sindji, Laurence Cayon, Jérôme Fillesoye, Fabien Toutain, Jérôme Divoux, Didier Marteau, Léna Lecocq, Myriam Roussel, Simon Montero-Menei, Claudia N. Bernaudin, Myriam |
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Few effective therapeutic interventions are available to limit brain damage and functional deficits after ischaemic stroke. Within this context, mesenchymal stem cell (MSC) therapy carries minimal risks while remaining efficacious through the secretion of trophic, protective, neurogenic and angiogenic factors. The limited survival rate of MSCs restricts their beneficial effects. The usefulness of a three-dimensional support, such as a pharmacologically active microcarrier (PAM), on the survival of MSCs during hypoxia has been shown in vitro, especially when the PAMs were loaded with vascular endothelial growth factor (VEGF). In the present study, the effect of MSCs attached to laminin-PAMs (LM-PAMs), releasing VEGF or not, was evaluated in vivo in a model of transient stroke. The parameters assessed were infarct volume, functional recovery and endogenous cellular reactions. LM-PAMs induced the expression of neuronal markers by MSCs both in vitro and in vivo. Moreover, the prolonged release of VEGF increased angiogenesis around the site of implantation of the LM-PAMs and facilitated the migration of immature neurons towards the ischaemic tissue. Nonetheless, MSCs/LM-PAMs–VEGF failed to improve sensorimotor functions. The use of LM-PAMs to convey MSCs and to deliver growth factors could be an effective strategy to repair the brain damage caused by a stroke. |
| doi_str_mv | 10.1016/j.actbio.2014.12.017 |
| format | Article |
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Few effective therapeutic interventions are available to limit brain damage and functional deficits after ischaemic stroke. Within this context, mesenchymal stem cell (MSC) therapy carries minimal risks while remaining efficacious through the secretion of trophic, protective, neurogenic and angiogenic factors. The limited survival rate of MSCs restricts their beneficial effects. The usefulness of a three-dimensional support, such as a pharmacologically active microcarrier (PAM), on the survival of MSCs during hypoxia has been shown in vitro, especially when the PAMs were loaded with vascular endothelial growth factor (VEGF). In the present study, the effect of MSCs attached to laminin-PAMs (LM-PAMs), releasing VEGF or not, was evaluated in vivo in a model of transient stroke. The parameters assessed were infarct volume, functional recovery and endogenous cellular reactions. LM-PAMs induced the expression of neuronal markers by MSCs both in vitro and in vivo. Moreover, the prolonged release of VEGF increased angiogenesis around the site of implantation of the LM-PAMs and facilitated the migration of immature neurons towards the ischaemic tissue. Nonetheless, MSCs/LM-PAMs–VEGF failed to improve sensorimotor functions. The use of LM-PAMs to convey MSCs and to deliver growth factors could be an effective strategy to repair the brain damage caused by a stroke.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2014.12.017</identifier><identifier>PMID: 25556361</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Angiogenesis ; Animals ; Behavior, Animal ; Biomedical materials ; Blood Vessels - drug effects ; Brain damage ; Brain Ischemia - complications ; Brain Ischemia - physiopathology ; Disease Models, Animal ; Drug Carriers - chemistry ; In vitro testing ; In vivo tests ; Infarction, Middle Cerebral Artery - complications ; Infarction, Middle Cerebral Artery - pathology ; Laminin - pharmacology ; Life Sciences ; Magnetic Resonance Imaging ; Male ; Mathematical models ; Mesenchymal Stem Cell Transplantation ; Mesenchymal stem cells ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - drug effects ; Microtubule-Associated Proteins - metabolism ; Neuropeptides - metabolism ; Pharmacologically active microcarriers ; Rats, Sprague-Dawley ; Recovery of Function - drug effects ; Releasing ; Stroke ; Stroke - drug therapy ; Stroke - etiology ; Stroke - physiopathology ; Strokes ; Surgical implants ; Therapy ; Treatment Outcome ; Vascular Endothelial Growth Factor A - pharmacology ; Vascular Endothelial Growth Factor A - therapeutic use ; VEGF</subject><ispartof>Acta biomaterialia, 2015-03, Vol.15 (15), p.77-88</ispartof><rights>2014 Acta Materialia Inc.</rights><rights>Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-2af34c5f98313a3ae7bcb0a41777a99f616406d747897992c9fbd24b32a4d65e3</citedby><cites>FETCH-LOGICAL-c532t-2af34c5f98313a3ae7bcb0a41777a99f616406d747897992c9fbd24b32a4d65e3</cites><orcidid>0000-0002-1373-6987 ; 0000-0003-0778-3397 ; 0000-0001-5449-4817 ; 0000-0001-9031-0907</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1742706114005819$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25556361$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01577870$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Quittet, Marie-Sophie</creatorcontrib><creatorcontrib>Touzani, Omar</creatorcontrib><creatorcontrib>Sindji, Laurence</creatorcontrib><creatorcontrib>Cayon, Jérôme</creatorcontrib><creatorcontrib>Fillesoye, Fabien</creatorcontrib><creatorcontrib>Toutain, Jérôme</creatorcontrib><creatorcontrib>Divoux, Didier</creatorcontrib><creatorcontrib>Marteau, Léna</creatorcontrib><creatorcontrib>Lecocq, Myriam</creatorcontrib><creatorcontrib>Roussel, Simon</creatorcontrib><creatorcontrib>Montero-Menei, Claudia N.</creatorcontrib><creatorcontrib>Bernaudin, Myriam</creatorcontrib><title>Effects of mesenchymal stem cell therapy, in association with pharmacologically active microcarriers releasing VEGF, in an ischaemic stroke model in the rat</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>[Display omitted]
Few effective therapeutic interventions are available to limit brain damage and functional deficits after ischaemic stroke. Within this context, mesenchymal stem cell (MSC) therapy carries minimal risks while remaining efficacious through the secretion of trophic, protective, neurogenic and angiogenic factors. The limited survival rate of MSCs restricts their beneficial effects. The usefulness of a three-dimensional support, such as a pharmacologically active microcarrier (PAM), on the survival of MSCs during hypoxia has been shown in vitro, especially when the PAMs were loaded with vascular endothelial growth factor (VEGF). In the present study, the effect of MSCs attached to laminin-PAMs (LM-PAMs), releasing VEGF or not, was evaluated in vivo in a model of transient stroke. The parameters assessed were infarct volume, functional recovery and endogenous cellular reactions. LM-PAMs induced the expression of neuronal markers by MSCs both in vitro and in vivo. Moreover, the prolonged release of VEGF increased angiogenesis around the site of implantation of the LM-PAMs and facilitated the migration of immature neurons towards the ischaemic tissue. Nonetheless, MSCs/LM-PAMs–VEGF failed to improve sensorimotor functions. The use of LM-PAMs to convey MSCs and to deliver growth factors could be an effective strategy to repair the brain damage caused by a stroke.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Behavior, Animal</subject><subject>Biomedical materials</subject><subject>Blood Vessels - drug effects</subject><subject>Brain damage</subject><subject>Brain Ischemia - complications</subject><subject>Brain Ischemia - physiopathology</subject><subject>Disease Models, Animal</subject><subject>Drug Carriers - chemistry</subject><subject>In vitro testing</subject><subject>In vivo tests</subject><subject>Infarction, Middle Cerebral Artery - complications</subject><subject>Infarction, Middle Cerebral Artery - pathology</subject><subject>Laminin - pharmacology</subject><subject>Life Sciences</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Mathematical models</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - drug effects</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Neuropeptides - metabolism</subject><subject>Pharmacologically active microcarriers</subject><subject>Rats, Sprague-Dawley</subject><subject>Recovery of Function - drug effects</subject><subject>Releasing</subject><subject>Stroke</subject><subject>Stroke - drug therapy</subject><subject>Stroke - etiology</subject><subject>Stroke - physiopathology</subject><subject>Strokes</subject><subject>Surgical implants</subject><subject>Therapy</subject><subject>Treatment Outcome</subject><subject>Vascular Endothelial Growth Factor A - pharmacology</subject><subject>Vascular Endothelial Growth Factor A - therapeutic use</subject><subject>VEGF</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks1u1DAUhSMEoqXwBgh5CRIz-N_xBqmqpi1SJTbA1rpxbhoPSTzYmUHzLjwsHqV0ibqyZX_3nuPrU1VvGV0zyvSn7Rr83IS45pTJNeNrysyz6pzVpl4ZpevnZW8kXxmq2Vn1KuctpaJmvH5ZnXGllBaanVd_Nl2Hfs4kdmTEjJPvjyMMJM84Eo_DQOYeE-yOH0mYCOQcfYA5xIn8DnNPdj2kEXwc4n3wMAxHUkyFA5Ix-BQ9pBQwZZJwQMhhuic_NjfXS6uJhOx7wEIWtRR_lqLY4nC6LJokwfy6etHBkPHNw3pRfb_efLu6Xd19vflydXm38krwecWhE9KrztaCCRCApvENBcmMMWBtp5mWVLdGmtoaa7m3XdNy2QgOstUKxUX1Yenbw-B2KYyQji5CcLeXd-50Rpkypjb0wAr7fmF3Kf7aY57dWN5RBgUTxn12TJuiYblUT0GFqC2z5gmo0lQqZm1B5YKWAeecsHt0zKg7JcNt3ZIMd0qGY7zYPym8e1DYNyO2j0X_olCAzwuAZdKH8m0u-1DygG1IJSGujeH_Cn8BVYnMLg</recordid><startdate>201503</startdate><enddate>201503</enddate><creator>Quittet, Marie-Sophie</creator><creator>Touzani, Omar</creator><creator>Sindji, Laurence</creator><creator>Cayon, Jérôme</creator><creator>Fillesoye, Fabien</creator><creator>Toutain, Jérôme</creator><creator>Divoux, Didier</creator><creator>Marteau, Léna</creator><creator>Lecocq, Myriam</creator><creator>Roussel, Simon</creator><creator>Montero-Menei, Claudia N.</creator><creator>Bernaudin, Myriam</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>L7M</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-1373-6987</orcidid><orcidid>https://orcid.org/0000-0003-0778-3397</orcidid><orcidid>https://orcid.org/0000-0001-5449-4817</orcidid><orcidid>https://orcid.org/0000-0001-9031-0907</orcidid></search><sort><creationdate>201503</creationdate><title>Effects of mesenchymal stem cell therapy, in association with pharmacologically active microcarriers releasing VEGF, in an ischaemic stroke model in the rat</title><author>Quittet, Marie-Sophie ; Touzani, Omar ; Sindji, Laurence ; Cayon, Jérôme ; Fillesoye, Fabien ; Toutain, Jérôme ; Divoux, Didier ; Marteau, Léna ; Lecocq, Myriam ; Roussel, Simon ; Montero-Menei, Claudia N. ; Bernaudin, Myriam</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-2af34c5f98313a3ae7bcb0a41777a99f616406d747897992c9fbd24b32a4d65e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Angiogenesis</topic><topic>Animals</topic><topic>Behavior, Animal</topic><topic>Biomedical materials</topic><topic>Blood Vessels - drug effects</topic><topic>Brain damage</topic><topic>Brain Ischemia - complications</topic><topic>Brain Ischemia - physiopathology</topic><topic>Disease Models, Animal</topic><topic>Drug Carriers - chemistry</topic><topic>In vitro testing</topic><topic>In vivo tests</topic><topic>Infarction, Middle Cerebral Artery - complications</topic><topic>Infarction, Middle Cerebral Artery - pathology</topic><topic>Laminin - pharmacology</topic><topic>Life Sciences</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Mathematical models</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchymal Stromal Cells - drug effects</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Neuropeptides - metabolism</topic><topic>Pharmacologically active microcarriers</topic><topic>Rats, Sprague-Dawley</topic><topic>Recovery of Function - drug effects</topic><topic>Releasing</topic><topic>Stroke</topic><topic>Stroke - drug therapy</topic><topic>Stroke - etiology</topic><topic>Stroke - physiopathology</topic><topic>Strokes</topic><topic>Surgical implants</topic><topic>Therapy</topic><topic>Treatment Outcome</topic><topic>Vascular Endothelial Growth Factor A - pharmacology</topic><topic>Vascular Endothelial Growth Factor A - therapeutic use</topic><topic>VEGF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Quittet, Marie-Sophie</creatorcontrib><creatorcontrib>Touzani, Omar</creatorcontrib><creatorcontrib>Sindji, Laurence</creatorcontrib><creatorcontrib>Cayon, Jérôme</creatorcontrib><creatorcontrib>Fillesoye, Fabien</creatorcontrib><creatorcontrib>Toutain, Jérôme</creatorcontrib><creatorcontrib>Divoux, Didier</creatorcontrib><creatorcontrib>Marteau, Léna</creatorcontrib><creatorcontrib>Lecocq, Myriam</creatorcontrib><creatorcontrib>Roussel, Simon</creatorcontrib><creatorcontrib>Montero-Menei, Claudia N.</creatorcontrib><creatorcontrib>Bernaudin, Myriam</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Acta biomaterialia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Quittet, Marie-Sophie</au><au>Touzani, Omar</au><au>Sindji, Laurence</au><au>Cayon, Jérôme</au><au>Fillesoye, Fabien</au><au>Toutain, Jérôme</au><au>Divoux, Didier</au><au>Marteau, Léna</au><au>Lecocq, Myriam</au><au>Roussel, Simon</au><au>Montero-Menei, Claudia N.</au><au>Bernaudin, Myriam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of mesenchymal stem cell therapy, in association with pharmacologically active microcarriers releasing VEGF, in an ischaemic stroke model in the rat</atitle><jtitle>Acta biomaterialia</jtitle><addtitle>Acta Biomater</addtitle><date>2015-03</date><risdate>2015</risdate><volume>15</volume><issue>15</issue><spage>77</spage><epage>88</epage><pages>77-88</pages><issn>1742-7061</issn><eissn>1878-7568</eissn><abstract>[Display omitted]
Few effective therapeutic interventions are available to limit brain damage and functional deficits after ischaemic stroke. Within this context, mesenchymal stem cell (MSC) therapy carries minimal risks while remaining efficacious through the secretion of trophic, protective, neurogenic and angiogenic factors. The limited survival rate of MSCs restricts their beneficial effects. The usefulness of a three-dimensional support, such as a pharmacologically active microcarrier (PAM), on the survival of MSCs during hypoxia has been shown in vitro, especially when the PAMs were loaded with vascular endothelial growth factor (VEGF). In the present study, the effect of MSCs attached to laminin-PAMs (LM-PAMs), releasing VEGF or not, was evaluated in vivo in a model of transient stroke. The parameters assessed were infarct volume, functional recovery and endogenous cellular reactions. LM-PAMs induced the expression of neuronal markers by MSCs both in vitro and in vivo. Moreover, the prolonged release of VEGF increased angiogenesis around the site of implantation of the LM-PAMs and facilitated the migration of immature neurons towards the ischaemic tissue. Nonetheless, MSCs/LM-PAMs–VEGF failed to improve sensorimotor functions. The use of LM-PAMs to convey MSCs and to deliver growth factors could be an effective strategy to repair the brain damage caused by a stroke.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>25556361</pmid><doi>10.1016/j.actbio.2014.12.017</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-1373-6987</orcidid><orcidid>https://orcid.org/0000-0003-0778-3397</orcidid><orcidid>https://orcid.org/0000-0001-5449-4817</orcidid><orcidid>https://orcid.org/0000-0001-9031-0907</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1742-7061 |
| ispartof | Acta biomaterialia, 2015-03, Vol.15 (15), p.77-88 |
| issn | 1742-7061 1878-7568 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_01577870v1 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Angiogenesis Animals Behavior, Animal Biomedical materials Blood Vessels - drug effects Brain damage Brain Ischemia - complications Brain Ischemia - physiopathology Disease Models, Animal Drug Carriers - chemistry In vitro testing In vivo tests Infarction, Middle Cerebral Artery - complications Infarction, Middle Cerebral Artery - pathology Laminin - pharmacology Life Sciences Magnetic Resonance Imaging Male Mathematical models Mesenchymal Stem Cell Transplantation Mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - drug effects Microtubule-Associated Proteins - metabolism Neuropeptides - metabolism Pharmacologically active microcarriers Rats, Sprague-Dawley Recovery of Function - drug effects Releasing Stroke Stroke - drug therapy Stroke - etiology Stroke - physiopathology Strokes Surgical implants Therapy Treatment Outcome Vascular Endothelial Growth Factor A - pharmacology Vascular Endothelial Growth Factor A - therapeutic use VEGF |
| title | Effects of mesenchymal stem cell therapy, in association with pharmacologically active microcarriers releasing VEGF, in an ischaemic stroke model in the rat |
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