title: Adenovirus vector-mediated ex vivo gene transfer of brain-derived neurotrophic factor (BDNF) tohuman umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) promotescrush-injured rat sciatic nerve regeneration.
abstract: This study was designed toinvestigate the efficacy of adenovirus vector-mediated brain-derived neurotrophic factor (BDNF) ex vivo gene transfer to human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) in a rat sciatic nerve crush injury model. BDNF protein and mRNA expression after infection was checked through an enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). Male Sprague-Dawley rats (200-250g, 6 weeks old) were distributed into threegroups (n=20 each): the control group, UCB-MSC group, and BDNF-adenovirus infected UCB-MSC (BDNF-Ad+UCB-MSC) group. UCB-MSCs (1×106cells/10μl/rat) or BDNF-Ad+UCB-MSCs (1×106cells/10μl/rat)were transplantedinto the rats at the crush site immediately after sciatic nerve injury. Cell tracking was done with PKH26-labeled UCB-MSCs and BDNF-Ad+UCB-MSCs (1×106cells/10μl/rat). The rats were monitored for 4 weeks post-surgery. Results showed that expression of BDNF at both the protein and mRNA levels was higher inthe BDNF-Ad+UCB-MSC group compared to theUCB-MSC group in vitro.Moreover, BDNF mRNA expression was higher in both UCB-MSC group and BDNF-Ad+ UCB-MSC group compared tothe control group, and BDNF mRNA expression in theBDNF-Ad+UCB-MSC group was higher than inboth other groups 5days after surgeryin vivo. Labeled neurons in the dorsal root ganglia (DRG), axon counts, axon density, and sciatic function index were significantly increased in the UCB-MSC and BDNF-Ad+ UCB-MSCgroupscompared to the controlgroup four weeksaftercell transplantation. Importantly,the BDNF-Ad+UCB-MSCgroup exhibited more peripheral nerve regeneration than the other two groups.Our results indicate thatboth UCB-MSCs and BDNF-Ad+UCB-MSCscan improve rat sciatic nerve regeneration, with BDNF-Ad+UCB-MSCsshowing a greater effectthan UCB-MSCs.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul, Republic of Korea; The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Hei
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul, Republic of Korea; Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Akram A
authors.initials: AA
authors.lastname: Almansoori
authors.affiliation: Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Mi-Ae
authors.initials: MA
authors.lastname: Sung
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul, Republic of Korea; Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Kyung-Won
authors.initials: KW
authors.lastname: Ju
authors.affiliation: Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Nari
authors.initials: N
authors.lastname: Seo
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul, Republic of Korea; Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Clinical Translational Research Center for Dental Science (CTRC), Seoul National University Dental Hospital, Seoul, Republic of Korea.
authors.forename: Bong-Ju
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Soung-Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Jahng
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Orthodontics, School and hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address: drhehong@hotmail.com.
authors.forename: Hong
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul, Republic of Korea; Dental Research Institute, Seoul National University, Seoul, Republic of Korea. Electronic address: leejongh@snu.ac.kr.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001369:Axons / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D005312:Fetal Blood; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: Brain-derived neurotrophic factor (BDNF); Human umbilical cord blood-derived mesenchymal stem cells; Peripheral nerve regeneration