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Article: Implantation of adult bone marrow-derived mesenchymal stem cells transfected with the neurotrophin-3 gene and pretreated with retinoic acid in completely transected spinal cord

TitleImplantation of adult bone marrow-derived mesenchymal stem cells transfected with the neurotrophin-3 gene and pretreated with retinoic acid in completely transected spinal cord
Authors
Issue Date2010
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/brainres
Citation
Brain Research, 2010, v. 1359, p. 256-271 How to Cite?
AbstractImplantation of marrow-derived mesenchymal stem cells (MSCs) is the most promising therapeutic strategy for the treatment of spinal cord injury (SCI), especially because of their potential for clinical application, such as the avoidance of immunologic rejection, their strong secretory properties, and their plasticity for developing into neural cells. However, the recovery from SCI after MSC implantation is minimal due to their limited capacity for the reduction of cystic cavitation, for the axonal regeneration and their uncertain neural plasticity in the spinal cord. We previously pretreated MSCs with all-trans retinoic acid (RA) in vitro. Then we genetically modified them to overexpress neurotrophin-3 (NT-3) via a recombinant adenoviral vector (Adv). This combined treatment not only permitted more neuronal differentiation of MSCs, but stimulated more NT-3 secretion prior to grafting, according to our previous and present results. When these cells were implanted into the transected spinal cord of rats, the animals had some improvement (both functionally and structurally), including the recovery of hindlimb locomotor function, shown by the highest Basso, Beattie, and Bresnahan (BBB) scores, as well as dramatically reduced cavity volume, clear axonal regeneration and more neuronal survival. In contrast, simple MSC implantation is not a very effective therapy for spinal transection. However, the neuronal differentiation of MSCs after treatment with a combination of Adv-mediated NT-3 gene transfer and RA was only mildly improved in vivo. © 2010 Elsevier B.V.
Persistent Identifierhttp://hdl.handle.net/10722/149749
ISSN
2015 Impact Factor: 2.561
2015 SCImago Journal Rankings: 1.351
ISI Accession Number ID
Funding AgencyGrant Number
Foundation of the Education Ministry of China2004558068
National Natural Science Foundation of China30771143
Guangdong Province Natural Science Foundation07117373
University of Hong Kong
National Key Basic Research Program of China2003CB515303
Funding Information:

This research was supported by grants from the Foundation of the Education Ministry of China (2004558068), the National Natural Science Foundation of China (30771143) and the Guangdong Province Natural Science Foundation (07117373) to Y.S. Zeng. The support of the University of Hong Kong and the National Key Basic Research Program of China (2003CB515303) to W. Wu is also gratefully acknowledged.

References

 

DC FieldValueLanguage
dc.contributor.authorZhang, Wen_US
dc.contributor.authorYan, Qen_US
dc.contributor.authorZeng, YSen_US
dc.contributor.authorZhang, XBen_US
dc.contributor.authorXiong, Yen_US
dc.contributor.authorWang, JMen_US
dc.contributor.authorChen, SJen_US
dc.contributor.authorLi, Yen_US
dc.contributor.authorBruce, ICen_US
dc.contributor.authorWu, Wen_US
dc.date.accessioned2012-06-26T05:57:59Z-
dc.date.available2012-06-26T05:57:59Z-
dc.date.issued2010en_US
dc.identifier.citationBrain Research, 2010, v. 1359, p. 256-271en_US
dc.identifier.issn0006-8993en_US
dc.identifier.urihttp://hdl.handle.net/10722/149749-
dc.description.abstractImplantation of marrow-derived mesenchymal stem cells (MSCs) is the most promising therapeutic strategy for the treatment of spinal cord injury (SCI), especially because of their potential for clinical application, such as the avoidance of immunologic rejection, their strong secretory properties, and their plasticity for developing into neural cells. However, the recovery from SCI after MSC implantation is minimal due to their limited capacity for the reduction of cystic cavitation, for the axonal regeneration and their uncertain neural plasticity in the spinal cord. We previously pretreated MSCs with all-trans retinoic acid (RA) in vitro. Then we genetically modified them to overexpress neurotrophin-3 (NT-3) via a recombinant adenoviral vector (Adv). This combined treatment not only permitted more neuronal differentiation of MSCs, but stimulated more NT-3 secretion prior to grafting, according to our previous and present results. When these cells were implanted into the transected spinal cord of rats, the animals had some improvement (both functionally and structurally), including the recovery of hindlimb locomotor function, shown by the highest Basso, Beattie, and Bresnahan (BBB) scores, as well as dramatically reduced cavity volume, clear axonal regeneration and more neuronal survival. In contrast, simple MSC implantation is not a very effective therapy for spinal transection. However, the neuronal differentiation of MSCs after treatment with a combination of Adv-mediated NT-3 gene transfer and RA was only mildly improved in vivo. © 2010 Elsevier B.V.en_US
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/brainresen_US
dc.relation.ispartofBrain Researchen_US
dc.subject.meshAdenoviridae - Geneticsen_US
dc.subject.meshAdult Stem Cells - Cytologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBone Marrow Cells - Cytologyen_US
dc.subject.meshCell Differentiation - Drug Effects - Geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshGenetic Vectorsen_US
dc.subject.meshImmunohistochemistryen_US
dc.subject.meshMesenchymal Stem Cell Transplantation - Methodsen_US
dc.subject.meshMesenchymal Stem Cells - Cytologyen_US
dc.subject.meshNerve Regeneration - Drug Effects - Geneticsen_US
dc.subject.meshNeurotrophin 3 - Geneticsen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshRecovery Of Functionen_US
dc.subject.meshSpinal Cord Injuries - Pathology - Surgeryen_US
dc.subject.meshTransfectionen_US
dc.subject.meshTretinoin - Pharmacologyen_US
dc.subject.meshVitamins - Pharmacologyen_US
dc.titleImplantation of adult bone marrow-derived mesenchymal stem cells transfected with the neurotrophin-3 gene and pretreated with retinoic acid in completely transected spinal corden_US
dc.typeArticleen_US
dc.identifier.emailWu, W:wtwu@hkucc.hku.hken_US
dc.identifier.authorityWu, W=rp00419en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.brainres.2010.08.072en_US
dc.identifier.pmid20816761-
dc.identifier.scopuseid_2-s2.0-77958006907en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77958006907&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume1359en_US
dc.identifier.spage256en_US
dc.identifier.epage271en_US
dc.identifier.isiWOS:000283976500026-
dc.publisher.placeNetherlandsen_US
dc.identifier.scopusauthoridZhang, W=36066941200en_US
dc.identifier.scopusauthoridYan, Q=36121837000en_US
dc.identifier.scopusauthoridZeng, YS=35263437100en_US
dc.identifier.scopusauthoridZhang, XB=49762336900en_US
dc.identifier.scopusauthoridXiong, Y=36136013000en_US
dc.identifier.scopusauthoridWang, JM=37035459900en_US
dc.identifier.scopusauthoridChen, SJ=14627353400en_US
dc.identifier.scopusauthoridLi, Y=36078298200en_US
dc.identifier.scopusauthoridBruce, IC=35612490700en_US
dc.identifier.scopusauthoridWu, W=7407081122en_US

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