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Comparison of intraspinal and intrathecal implantation of induced pluripotent stem cell-derived neural precursors for the treatment of spinal cord injury in rats
T. Amemori, J. Ruzicka, N. Romanyuk, M. Jhanwar-Uniyal, E. Sykova, P. Jendelova,
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem
NLK
BioMedCentral
od 2010-03-01
BioMedCentral Open Access
od 2010
Directory of Open Access Journals
od 2010
Free Medical Journals
od 2010 do Před 1 rokem
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od 2010
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od 2010
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od 2015-01-01
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od 2010-01-01
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od 2010-01-01
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- MeSH
- buněčná diferenciace MeSH
- indukované pluripotentní kmenové buňky cytologie transplantace MeSH
- krysa rodu rattus MeSH
- lokomoce MeSH
- nervové kmenové buňky cytologie transplantace MeSH
- parakrinní signalizace MeSH
- poranění míchy patologie patofyziologie terapie MeSH
- potkani Wistar MeSH
- proteiny nervové tkáně genetika metabolismus MeSH
- regenerace nervu MeSH
- spinální injekce metody MeSH
- viabilita buněk MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
BACKGROUND: Stem cell treatment provides a promising therapy for patients with spinal cord injury (SCI). However, the applied stem cells exert their effects in different manners that are dependent on the route used for administration. METHODS: In the present study, we administered neural precursors derived from induced pluripotent stem cells (iPS-NPs) either intraspinally into the lesion center or intrathecally into the subarachnoid space of rats with a balloon-induced spinal cord compression lesion. Functional locomotor performance, cell survival, astrogliosis, axonal sprouting and the expression of endogenous neurotrophic growth factors were evaluated using behavioral tests (BBB, flat beam test, rotarod, plantar test), morphometric analysis, immunohistochemistry and qPCR. RESULTS: Both treatments facilitated the functional locomotor recovery of rats with SCI. iPS-NPs injected intraspinally survived well for 2 months and were positive for MAP2, while cells grafted intrathecally were undetectable at the site of administration or in the spinal cord tissue. Intraspinal implantation increased gray and white matter sparing and axonal sprouting and reduced astrogliosis, while intrathecal application resulted only in an improvement of white matter sparing and an increase in axonal sprouting, in parallel with no positive effect on the expression of endogenous neurotrophic growth factor genes or glial scar reduction. CONCLUSIONS: Intrathecally grafted iPS-NPs had a moderate therapeutic benefit on SCI through a paracrine mechanism that does not require the cells to be present in the tissue; however, the extended survival of i.s. grafted cells in the spinal cord may promote long-term spinal cord tissue regeneration.
Citace poskytuje Crossref.org
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- $a Amemori, Takashi $u Department of Neuroscience, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20, Prague 4, Czech Republic. amemori@biomed.cas.cz. $7 gn_A_00005511
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- $a BACKGROUND: Stem cell treatment provides a promising therapy for patients with spinal cord injury (SCI). However, the applied stem cells exert their effects in different manners that are dependent on the route used for administration. METHODS: In the present study, we administered neural precursors derived from induced pluripotent stem cells (iPS-NPs) either intraspinally into the lesion center or intrathecally into the subarachnoid space of rats with a balloon-induced spinal cord compression lesion. Functional locomotor performance, cell survival, astrogliosis, axonal sprouting and the expression of endogenous neurotrophic growth factors were evaluated using behavioral tests (BBB, flat beam test, rotarod, plantar test), morphometric analysis, immunohistochemistry and qPCR. RESULTS: Both treatments facilitated the functional locomotor recovery of rats with SCI. iPS-NPs injected intraspinally survived well for 2 months and were positive for MAP2, while cells grafted intrathecally were undetectable at the site of administration or in the spinal cord tissue. Intraspinal implantation increased gray and white matter sparing and axonal sprouting and reduced astrogliosis, while intrathecal application resulted only in an improvement of white matter sparing and an increase in axonal sprouting, in parallel with no positive effect on the expression of endogenous neurotrophic growth factor genes or glial scar reduction. CONCLUSIONS: Intrathecally grafted iPS-NPs had a moderate therapeutic benefit on SCI through a paracrine mechanism that does not require the cells to be present in the tissue; however, the extended survival of i.s. grafted cells in the spinal cord may promote long-term spinal cord tissue regeneration.
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- $a Ruzicka, Jiri $u Department of Neuroscience, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20, Prague 4, Czech Republic. j.ruzicka@biomed.cas.cz. Department of Neuroscience, 2nd Faculty of Medicine, Charles University, Plzenska 130/221, 150 00, Prague 5, Czech Republic. j.ruzicka@biomed.cas.cz.
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