Human Cerebral Organoid Implantation Alleviated the Neurological Deficits of Traumatic Brain Injury in Mice
Traumatic brain injury (TBI) causes a high rate of mortality and disability, and its treatment is still limited. Loss of neurons in damaged area is hardly rescued by relative molecular therapies. Based on its disease characteristics, we transplanted human embryonic stem cell- (hESC-) derived cerebra...
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| Veröffentlicht in: | Oxidative medicine and cellular longevity 2021, Vol.2021 (1), p.6338722 |
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| container_title | Oxidative medicine and cellular longevity |
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| creator | Bao, Zhongyuan Fang, Kaiheng Miao, Zong Li, Chong Yang, Chaojuan Yu, Qiang Zhang, Chen Miao, Zengli Liu, Yan Ji, Jing |
| description | Traumatic brain injury (TBI) causes a high rate of mortality and disability, and its treatment is still limited. Loss of neurons in damaged area is hardly rescued by relative molecular therapies. Based on its disease characteristics, we transplanted human embryonic stem cell- (hESC-) derived cerebral organoids in the brain lesions of controlled cortical impact- (CCI-) modeled severe combined immunodeficient (SCID) mice. Grafted organoids survived and differentiated in CCI-induced lesion pools in mouse cortical tissue. Implanted cerebral organoids differentiated into various types of neuronal cells, extended long projections, and showed spontaneous action, as indicated by electromyographic activity in the grafts. Induced vascularization and reduced glial scar were also found after organoid implantation, suggesting grafting could improve local situation and promote neural repair. More importantly, the CCI mice’s spatial learning and memory improved after organoid grafting. These findings suggest that cerebral organoid implanted in lesion sites differentiates into cortical neurons, forms long projections, and reverses deficits in spatial learning and memory, a potential therapeutic avenue for TBI. |
| doi_str_mv | 10.1155/2021/6338722 |
| format | Article |
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Loss of neurons in damaged area is hardly rescued by relative molecular therapies. Based on its disease characteristics, we transplanted human embryonic stem cell- (hESC-) derived cerebral organoids in the brain lesions of controlled cortical impact- (CCI-) modeled severe combined immunodeficient (SCID) mice. Grafted organoids survived and differentiated in CCI-induced lesion pools in mouse cortical tissue. Implanted cerebral organoids differentiated into various types of neuronal cells, extended long projections, and showed spontaneous action, as indicated by electromyographic activity in the grafts. Induced vascularization and reduced glial scar were also found after organoid implantation, suggesting grafting could improve local situation and promote neural repair. More importantly, the CCI mice’s spatial learning and memory improved after organoid grafting. These findings suggest that cerebral organoid implanted in lesion sites differentiates into cortical neurons, forms long projections, and reverses deficits in spatial learning and memory, a potential therapeutic avenue for TBI.</description><identifier>ISSN: 1942-0900</identifier><identifier>EISSN: 1942-0994</identifier><identifier>DOI: 10.1155/2021/6338722</identifier><identifier>PMID: 34853630</identifier><language>eng</language><publisher>United States: Hindawi</publisher><subject>Animals ; Cerebral Cortex - pathology ; Disease Models, Animal ; Experiments ; Humans ; Laboratory animals ; Male ; Medical research ; Mice ; Mice, SCID ; Organoids - transplantation ; Stem cells ; Transfection ; Traumatic brain injury</subject><ispartof>Oxidative medicine and cellular longevity, 2021, Vol.2021 (1), p.6338722</ispartof><rights>Copyright © 2021 Zhongyuan Bao et al.</rights><rights>Copyright © 2021 Zhongyuan Bao et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2021 Zhongyuan Bao et al. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3302-f94cbdc07b6bd6613c0539ebeece3891116531b9b27895fbdeefb673cd9d2f513</citedby><cites>FETCH-LOGICAL-c3302-f94cbdc07b6bd6613c0539ebeece3891116531b9b27895fbdeefb673cd9d2f513</cites><orcidid>0000-0003-2918-5398 ; 0000-0002-7372-024X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629662/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629662/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,4009,27902,27903,27904,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34853630$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tang, Hailiang</contributor><contributor>Hailiang Tang</contributor><creatorcontrib>Bao, Zhongyuan</creatorcontrib><creatorcontrib>Fang, Kaiheng</creatorcontrib><creatorcontrib>Miao, Zong</creatorcontrib><creatorcontrib>Li, Chong</creatorcontrib><creatorcontrib>Yang, Chaojuan</creatorcontrib><creatorcontrib>Yu, Qiang</creatorcontrib><creatorcontrib>Zhang, Chen</creatorcontrib><creatorcontrib>Miao, Zengli</creatorcontrib><creatorcontrib>Liu, Yan</creatorcontrib><creatorcontrib>Ji, Jing</creatorcontrib><title>Human Cerebral Organoid Implantation Alleviated the Neurological Deficits of Traumatic Brain Injury in Mice</title><title>Oxidative medicine and cellular longevity</title><addtitle>Oxid Med Cell Longev</addtitle><description>Traumatic brain injury (TBI) causes a high rate of mortality and disability, and its treatment is still limited. 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These findings suggest that cerebral organoid implanted in lesion sites differentiates into cortical neurons, forms long projections, and reverses deficits in spatial learning and memory, a potential therapeutic avenue for TBI.</description><subject>Animals</subject><subject>Cerebral Cortex - pathology</subject><subject>Disease Models, Animal</subject><subject>Experiments</subject><subject>Humans</subject><subject>Laboratory animals</subject><subject>Male</subject><subject>Medical research</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Organoids - transplantation</subject><subject>Stem cells</subject><subject>Transfection</subject><subject>Traumatic brain injury</subject><issn>1942-0900</issn><issn>1942-0994</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kctPGzEQhy1ExSNw44wscSwpfuw66wsSBCiRAlzgbPkxmzhs7ODdpeK_xyghai89eSR_882MfgidUPKL0rK8YITRC8F5NWJsBx1QWbAhkbLY3daE7KPDtl0QIjgr6B7a50VVcsHJAXq975c64DEkMEk3-CnNdIje4cly1ejQ6c7HgK-aBt697sDhbg74EfoUmzjzNnfcQO2t71oca_ycdNZ13uLrpH3Ak7Do0wfO1YO3cIR-1Lpp4XjzDtDL3e3z-H44ffo9GV9Nh5Zzwoa1LKxxloyMME4Iyi0puQQDYIFXklIqSk6NNGxUybI2DqA2YsStk47VJeUDdLn2rnqzBGchdPk0tUp-qdOHitqrf3-Cn6tZfFeVYFIIlgVnG0GKbz20nVrEPoW8s2KCCCEIYTJT52vKpti2CertBErUVzTqKxq1iSbjp39vtYW_s8jAzzUw98HpP_7_uk_DgZfY</recordid><startdate>2021</startdate><enddate>2021</enddate><creator>Bao, Zhongyuan</creator><creator>Fang, Kaiheng</creator><creator>Miao, Zong</creator><creator>Li, Chong</creator><creator>Yang, Chaojuan</creator><creator>Yu, Qiang</creator><creator>Zhang, Chen</creator><creator>Miao, Zengli</creator><creator>Liu, Yan</creator><creator>Ji, Jing</creator><general>Hindawi</general><general>Hindawi Limited</general><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2918-5398</orcidid><orcidid>https://orcid.org/0000-0002-7372-024X</orcidid></search><sort><creationdate>2021</creationdate><title>Human Cerebral Organoid Implantation Alleviated the Neurological Deficits of Traumatic Brain Injury in Mice</title><author>Bao, Zhongyuan ; 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Loss of neurons in damaged area is hardly rescued by relative molecular therapies. Based on its disease characteristics, we transplanted human embryonic stem cell- (hESC-) derived cerebral organoids in the brain lesions of controlled cortical impact- (CCI-) modeled severe combined immunodeficient (SCID) mice. Grafted organoids survived and differentiated in CCI-induced lesion pools in mouse cortical tissue. Implanted cerebral organoids differentiated into various types of neuronal cells, extended long projections, and showed spontaneous action, as indicated by electromyographic activity in the grafts. Induced vascularization and reduced glial scar were also found after organoid implantation, suggesting grafting could improve local situation and promote neural repair. More importantly, the CCI mice’s spatial learning and memory improved after organoid grafting. These findings suggest that cerebral organoid implanted in lesion sites differentiates into cortical neurons, forms long projections, and reverses deficits in spatial learning and memory, a potential therapeutic avenue for TBI.</abstract><cop>United States</cop><pub>Hindawi</pub><pmid>34853630</pmid><doi>10.1155/2021/6338722</doi><orcidid>https://orcid.org/0000-0003-2918-5398</orcidid><orcidid>https://orcid.org/0000-0002-7372-024X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Cerebral Cortex - pathology Disease Models, Animal Experiments Humans Laboratory animals Male Medical research Mice Mice, SCID Organoids - transplantation Stem cells Transfection Traumatic brain injury |
| title | Human Cerebral Organoid Implantation Alleviated the Neurological Deficits of Traumatic Brain Injury in Mice |
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