Generation and post-injury integration of human spinal cord neural stem cells
Spinal cord neural stem cells (NSCs) have great potential to reconstitute damaged spinal neural circuitry, but they have yet to be generated in vitro. We now report the derivation of spinal cord NSCs from human pluripotent stem cells (hPSCs). Our observations show that these spinal cord NSCs differe...
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| Veröffentlicht in: | Nature methods 2018-09, Vol.15 (9), p.723-731 |
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| creator | Kumamaru, Hiromi Kadoya, Ken Adler, Andrew F. Takashima, Yoshio Graham, Lori Coppola, Giovanni Tuszynski, Mark H. |
| description | Spinal cord neural stem cells (NSCs) have great potential to reconstitute damaged spinal neural circuitry, but they have yet to be generated in vitro. We now report the derivation of spinal cord NSCs from human pluripotent stem cells (hPSCs). Our observations show that these spinal cord NSCs differentiate into a diverse population of spinal cord neurons occupying multiple positions along the dorso-ventral axis, and can be maintained for prolonged time periods. Grafts into injured spinal cords were rich with excitatory neurons, extended large numbers of axons over long distances, innervated their target structures, and enabled robust corticospinal regeneration. The grafts synaptically integrated into multiple host intraspinal and supraspinal systems, including the corticospinal projection, and improved functional outcomes after injury. hPSC-derived spinal cord NSCs could enable a broad range of biomedical applications for in vitro disease modeling and constitute an improved clinically translatable cell source for ‘replacement’ strategies in several spinal cord disorders.
Spinal cord neural stem cells are generated from human pluripotent stem cells via a chemically defined, xeno-free method, and exhibit efficient and functional engraftment in rat spinal cord lesions. |
| doi_str_mv | 10.1038/s41592-018-0074-3 |
| format | Article |
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Spinal cord neural stem cells are generated from human pluripotent stem cells via a chemically defined, xeno-free method, and exhibit efficient and functional engraftment in rat spinal cord lesions.</description><identifier>ISSN: 1548-7091</identifier><identifier>EISSN: 1548-7105</identifier><identifier>DOI: 10.1038/s41592-018-0074-3</identifier><identifier>PMID: 30082899</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/378 ; 631/532/2182 ; Axon guidance ; Axons ; Bioinformatics ; Biological Microscopy ; Biological Techniques ; Biomedical and Life Sciences ; Biomedical engineering ; Biomedical Engineering/Biotechnology ; Biomedical materials ; Cell Lineage ; Circuits ; Grafts ; Humans ; Injuries ; Life Sciences ; Neural circuitry ; Neural networks ; Neural stem cells ; Neural Stem Cells - pathology ; Neurons ; Patient outcomes ; Pluripotency ; Pluripotent Stem Cells - pathology ; Proteomics ; Pyramidal tracts ; Regeneration ; Spinal cord ; Spinal Cord - pathology ; Spinal cord injuries ; Spinal Cord Injuries - pathology ; Stem cells</subject><ispartof>Nature methods, 2018-09, Vol.15 (9), p.723-731</ispartof><rights>The Author(s) 2018</rights><rights>COPYRIGHT 2018 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Sep 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c505t-c4bde1425dab9824254c5b86e216111632927cf72ab22d86fc52fa9ae7e44fa63</citedby><cites>FETCH-LOGICAL-c505t-c4bde1425dab9824254c5b86e216111632927cf72ab22d86fc52fa9ae7e44fa63</cites><orcidid>0000-0001-7135-5528 ; 0000-0003-4182-1481</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41592-018-0074-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41592-018-0074-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30082899$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kumamaru, Hiromi</creatorcontrib><creatorcontrib>Kadoya, Ken</creatorcontrib><creatorcontrib>Adler, Andrew F.</creatorcontrib><creatorcontrib>Takashima, Yoshio</creatorcontrib><creatorcontrib>Graham, Lori</creatorcontrib><creatorcontrib>Coppola, Giovanni</creatorcontrib><creatorcontrib>Tuszynski, Mark H.</creatorcontrib><title>Generation and post-injury integration of human spinal cord neural stem cells</title><title>Nature methods</title><addtitle>Nat Methods</addtitle><addtitle>Nat Methods</addtitle><description>Spinal cord neural stem cells (NSCs) have great potential to reconstitute damaged spinal neural circuitry, but they have yet to be generated in vitro. We now report the derivation of spinal cord NSCs from human pluripotent stem cells (hPSCs). Our observations show that these spinal cord NSCs differentiate into a diverse population of spinal cord neurons occupying multiple positions along the dorso-ventral axis, and can be maintained for prolonged time periods. Grafts into injured spinal cords were rich with excitatory neurons, extended large numbers of axons over long distances, innervated their target structures, and enabled robust corticospinal regeneration. The grafts synaptically integrated into multiple host intraspinal and supraspinal systems, including the corticospinal projection, and improved functional outcomes after injury. hPSC-derived spinal cord NSCs could enable a broad range of biomedical applications for in vitro disease modeling and constitute an improved clinically translatable cell source for ‘replacement’ strategies in several spinal cord disorders.
Spinal cord neural stem cells are generated from human pluripotent stem cells via a chemically defined, xeno-free method, and exhibit efficient and functional engraftment in rat spinal cord lesions.</description><subject>631/378</subject><subject>631/532/2182</subject><subject>Axon guidance</subject><subject>Axons</subject><subject>Bioinformatics</subject><subject>Biological Microscopy</subject><subject>Biological Techniques</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical engineering</subject><subject>Biomedical Engineering/Biotechnology</subject><subject>Biomedical materials</subject><subject>Cell Lineage</subject><subject>Circuits</subject><subject>Grafts</subject><subject>Humans</subject><subject>Injuries</subject><subject>Life Sciences</subject><subject>Neural circuitry</subject><subject>Neural networks</subject><subject>Neural stem cells</subject><subject>Neural Stem Cells - pathology</subject><subject>Neurons</subject><subject>Patient outcomes</subject><subject>Pluripotency</subject><subject>Pluripotent Stem Cells - 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Academic</collection><jtitle>Nature methods</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kumamaru, Hiromi</au><au>Kadoya, Ken</au><au>Adler, Andrew F.</au><au>Takashima, Yoshio</au><au>Graham, Lori</au><au>Coppola, Giovanni</au><au>Tuszynski, Mark H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Generation and post-injury integration of human spinal cord neural stem cells</atitle><jtitle>Nature methods</jtitle><stitle>Nat Methods</stitle><addtitle>Nat Methods</addtitle><date>2018-09-01</date><risdate>2018</risdate><volume>15</volume><issue>9</issue><spage>723</spage><epage>731</epage><pages>723-731</pages><issn>1548-7091</issn><eissn>1548-7105</eissn><abstract>Spinal cord neural stem cells (NSCs) have great potential to reconstitute damaged spinal neural circuitry, but they have yet to be generated in vitro. We now report the derivation of spinal cord NSCs from human pluripotent stem cells (hPSCs). Our observations show that these spinal cord NSCs differentiate into a diverse population of spinal cord neurons occupying multiple positions along the dorso-ventral axis, and can be maintained for prolonged time periods. Grafts into injured spinal cords were rich with excitatory neurons, extended large numbers of axons over long distances, innervated their target structures, and enabled robust corticospinal regeneration. The grafts synaptically integrated into multiple host intraspinal and supraspinal systems, including the corticospinal projection, and improved functional outcomes after injury. hPSC-derived spinal cord NSCs could enable a broad range of biomedical applications for in vitro disease modeling and constitute an improved clinically translatable cell source for ‘replacement’ strategies in several spinal cord disorders.
Spinal cord neural stem cells are generated from human pluripotent stem cells via a chemically defined, xeno-free method, and exhibit efficient and functional engraftment in rat spinal cord lesions.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>30082899</pmid><doi>10.1038/s41592-018-0074-3</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-7135-5528</orcidid><orcidid>https://orcid.org/0000-0003-4182-1481</orcidid></addata></record> |
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| subjects | 631/378 631/532/2182 Axon guidance Axons Bioinformatics Biological Microscopy Biological Techniques Biomedical and Life Sciences Biomedical engineering Biomedical Engineering/Biotechnology Biomedical materials Cell Lineage Circuits Grafts Humans Injuries Life Sciences Neural circuitry Neural networks Neural stem cells Neural Stem Cells - pathology Neurons Patient outcomes Pluripotency Pluripotent Stem Cells - pathology Proteomics Pyramidal tracts Regeneration Spinal cord Spinal Cord - pathology Spinal cord injuries Spinal Cord Injuries - pathology Stem cells |
| title | Generation and post-injury integration of human spinal cord neural stem cells |
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