Immune remodelling of stromal cell grafts in the central nervous system: therapeutic inflammation or (harmless) side‐effect?
Over the past two decades, several cell types with fibroblast‐like morphology, including mesenchymal stem/stromal cells, but also other adult, embryonic and extra‐embryonic fibroblast‐like cells, have been brought forward in the search for cellular therapies to treat severe brain injuries and/or dis...
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| Veröffentlicht in: | Journal of tissue engineering and regenerative medicine 2017-10, Vol.11 (10), p.2846-2852 |
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| container_title | Journal of tissue engineering and regenerative medicine |
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| creator | Le Blon, Debbie Hoornaert, Chloé Detrez, Jan R. Bevers, Sanne Daans, Jasmijn Goossens, Herman De Vos, Winnok H. Berneman, Zwi Ponsaerts, Peter |
| description | Over the past two decades, several cell types with fibroblast‐like morphology, including mesenchymal stem/stromal cells, but also other adult, embryonic and extra‐embryonic fibroblast‐like cells, have been brought forward in the search for cellular therapies to treat severe brain injuries and/or diseases. Although current views in regenerative medicine are highly focused on the immune modulating and regenerative properties of stromal cell transplantation in vivo, many open questions remain regarding their true mode of action. In this perspective, this study integrates insights gathered over the past 10 years to formulate a unifying model of the cellular events that accompany fibroblast‐like cell grafting in the rodent brain. Cellular interactions are discussed step‐by‐step, starting from the day of implantation up to 10 days after transplantation. During the short period that precedes stable settlement of autologous/syngeneic stromal cell grafts, there is a complex interplay between hypoxia‐mediated cell death of grafted cells, neutrophil invasion, microglia and macrophage recruitment, astrocyte activation and neo‐angiogenesis within the stromal cell graft site. Consequently, it is speculated that regenerative processes following cell therapeutic intervention in the CNS are not only modulated by soluble factors secreted by grafted stromal cells (bystander hypothesis), but also by in vivo inflammatory processes following stromal cell grafting. Copyright © 2016 John Wiley & Sons, Ltd. |
| doi_str_mv | 10.1002/term.2188 |
| format | Article |
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Although current views in regenerative medicine are highly focused on the immune modulating and regenerative properties of stromal cell transplantation in vivo, many open questions remain regarding their true mode of action. In this perspective, this study integrates insights gathered over the past 10 years to formulate a unifying model of the cellular events that accompany fibroblast‐like cell grafting in the rodent brain. Cellular interactions are discussed step‐by‐step, starting from the day of implantation up to 10 days after transplantation. During the short period that precedes stable settlement of autologous/syngeneic stromal cell grafts, there is a complex interplay between hypoxia‐mediated cell death of grafted cells, neutrophil invasion, microglia and macrophage recruitment, astrocyte activation and neo‐angiogenesis within the stromal cell graft site. Consequently, it is speculated that regenerative processes following cell therapeutic intervention in the CNS are not only modulated by soluble factors secreted by grafted stromal cells (bystander hypothesis), but also by in vivo inflammatory processes following stromal cell grafting. Copyright © 2016 John Wiley & Sons, Ltd.</description><identifier>ISSN: 1932-6254</identifier><identifier>EISSN: 1932-7005</identifier><identifier>DOI: 10.1002/term.2188</identifier><identifier>PMID: 27320821</identifier><language>eng</language><publisher>England: Hindawi Limited</publisher><subject>Angiogenesis ; Animals ; Autografts ; Brain ; Brain injury ; Cell activation ; Cell death ; Central nervous system ; Central Nervous System - immunology ; Central Nervous System - pathology ; Cytology ; Embryo fibroblasts ; Fibroblasts ; Grafting ; Grafts ; graft‐remodelling ; Head injuries ; Humans ; Hypoxia ; Implantation ; Inflammation ; Inflammation - pathology ; Macrophages ; Mesenchyme ; Microglia ; Mode of action ; Models, Biological ; neuroinflammation ; neuroprotection ; Recruitment ; Regenerative medicine ; Stromal cells ; Stromal Cells - cytology ; Stromal Cells - immunology ; Stromal Cells - transplantation ; Surgical implants ; Tissue engineering ; Transplantation</subject><ispartof>Journal of tissue engineering and regenerative medicine, 2017-10, Vol.11 (10), p.2846-2852</ispartof><rights>Copyright © 2016 John Wiley & Sons, Ltd.</rights><rights>Copyright © 2017 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3548-6ce1a76843c682b2c59eb9a8f98be35df930e7ee37ace51ec4d688525ee802d83</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fterm.2188$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fterm.2188$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27320821$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Le Blon, Debbie</creatorcontrib><creatorcontrib>Hoornaert, Chloé</creatorcontrib><creatorcontrib>Detrez, Jan R.</creatorcontrib><creatorcontrib>Bevers, Sanne</creatorcontrib><creatorcontrib>Daans, Jasmijn</creatorcontrib><creatorcontrib>Goossens, Herman</creatorcontrib><creatorcontrib>De Vos, Winnok H.</creatorcontrib><creatorcontrib>Berneman, Zwi</creatorcontrib><creatorcontrib>Ponsaerts, Peter</creatorcontrib><title>Immune remodelling of stromal cell grafts in the central nervous system: therapeutic inflammation or (harmless) side‐effect?</title><title>Journal of tissue engineering and regenerative medicine</title><addtitle>J Tissue Eng Regen Med</addtitle><description>Over the past two decades, several cell types with fibroblast‐like morphology, including mesenchymal stem/stromal cells, but also other adult, embryonic and extra‐embryonic fibroblast‐like cells, have been brought forward in the search for cellular therapies to treat severe brain injuries and/or diseases. Although current views in regenerative medicine are highly focused on the immune modulating and regenerative properties of stromal cell transplantation in vivo, many open questions remain regarding their true mode of action. In this perspective, this study integrates insights gathered over the past 10 years to formulate a unifying model of the cellular events that accompany fibroblast‐like cell grafting in the rodent brain. Cellular interactions are discussed step‐by‐step, starting from the day of implantation up to 10 days after transplantation. During the short period that precedes stable settlement of autologous/syngeneic stromal cell grafts, there is a complex interplay between hypoxia‐mediated cell death of grafted cells, neutrophil invasion, microglia and macrophage recruitment, astrocyte activation and neo‐angiogenesis within the stromal cell graft site. Consequently, it is speculated that regenerative processes following cell therapeutic intervention in the CNS are not only modulated by soluble factors secreted by grafted stromal cells (bystander hypothesis), but also by in vivo inflammatory processes following stromal cell grafting. Copyright © 2016 John Wiley & Sons, Ltd.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Autografts</subject><subject>Brain</subject><subject>Brain injury</subject><subject>Cell activation</subject><subject>Cell death</subject><subject>Central nervous system</subject><subject>Central Nervous System - immunology</subject><subject>Central Nervous System - pathology</subject><subject>Cytology</subject><subject>Embryo fibroblasts</subject><subject>Fibroblasts</subject><subject>Grafting</subject><subject>Grafts</subject><subject>graft‐remodelling</subject><subject>Head injuries</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Implantation</subject><subject>Inflammation</subject><subject>Inflammation - pathology</subject><subject>Macrophages</subject><subject>Mesenchyme</subject><subject>Microglia</subject><subject>Mode of action</subject><subject>Models, Biological</subject><subject>neuroinflammation</subject><subject>neuroprotection</subject><subject>Recruitment</subject><subject>Regenerative medicine</subject><subject>Stromal cells</subject><subject>Stromal Cells - cytology</subject><subject>Stromal Cells - immunology</subject><subject>Stromal Cells - transplantation</subject><subject>Surgical implants</subject><subject>Tissue engineering</subject><subject>Transplantation</subject><issn>1932-6254</issn><issn>1932-7005</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc9KxDAQxoMouq4efAEJeFkPu-ZP06ZeRJb1D6wIoueQTadaado1SZW9iI_gM_okprh68DTD9_0YZuZD6ICSCSWEnQRwdsKolBtoQHPOxhkhYnPdp0wkO2jX--coilTwbbTDMs6IZHSA3q-t7RrADmxbQF1XzSNuS-yDa62usYkSfnS6DB5XDQ5PEKUmuGg14F7bzmO_8gHsae85vYQuVCaiZa2t1aFqG9w6PHrSztbg_TH2VQFfH59QlmDC2R7aKnXtYX9dh-jhYnY_vRrPby-vp-fzseEikePUANVZKhNuUskWzIgcFrmWZS4XwEVR5pxABsAzbUBQMEmRSimYAJCEFZIP0ehn7tK1Lx34oGzl--N0A_EIRSVLM0JZziN69A99bjvXxO0UzYWQjJEkidThmuoWFgq1dJXVbqV-PxuBkx_graph9edTovrIVB-Z6iNT97O7m77h3w94i4I</recordid><startdate>201710</startdate><enddate>201710</enddate><creator>Le Blon, Debbie</creator><creator>Hoornaert, Chloé</creator><creator>Detrez, Jan R.</creator><creator>Bevers, Sanne</creator><creator>Daans, Jasmijn</creator><creator>Goossens, Herman</creator><creator>De Vos, Winnok H.</creator><creator>Berneman, Zwi</creator><creator>Ponsaerts, Peter</creator><general>Hindawi Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201710</creationdate><title>Immune remodelling of stromal cell grafts in the central nervous system: therapeutic inflammation or (harmless) side‐effect?</title><author>Le Blon, Debbie ; 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Although current views in regenerative medicine are highly focused on the immune modulating and regenerative properties of stromal cell transplantation in vivo, many open questions remain regarding their true mode of action. In this perspective, this study integrates insights gathered over the past 10 years to formulate a unifying model of the cellular events that accompany fibroblast‐like cell grafting in the rodent brain. Cellular interactions are discussed step‐by‐step, starting from the day of implantation up to 10 days after transplantation. During the short period that precedes stable settlement of autologous/syngeneic stromal cell grafts, there is a complex interplay between hypoxia‐mediated cell death of grafted cells, neutrophil invasion, microglia and macrophage recruitment, astrocyte activation and neo‐angiogenesis within the stromal cell graft site. 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| ispartof | Journal of tissue engineering and regenerative medicine, 2017-10, Vol.11 (10), p.2846-2852 |
| issn | 1932-6254 1932-7005 |
| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Angiogenesis Animals Autografts Brain Brain injury Cell activation Cell death Central nervous system Central Nervous System - immunology Central Nervous System - pathology Cytology Embryo fibroblasts Fibroblasts Grafting Grafts graft‐remodelling Head injuries Humans Hypoxia Implantation Inflammation Inflammation - pathology Macrophages Mesenchyme Microglia Mode of action Models, Biological neuroinflammation neuroprotection Recruitment Regenerative medicine Stromal cells Stromal Cells - cytology Stromal Cells - immunology Stromal Cells - transplantation Surgical implants Tissue engineering Transplantation |
| title | Immune remodelling of stromal cell grafts in the central nervous system: therapeutic inflammation or (harmless) side‐effect? |
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