PMID- 17515814 OWN - NLM STAT- MEDLINE DCOM- 20070627 LR - 20090709 IS - 1528-1159 (Electronic) IS - 0362-2436 (Linking) VI - 32 IP - 12 DP - 2007 May 20 TI - BDNF, NT-3, and NGF released from transplanted neural progenitor cells promote corticospinal axon growth in organotypic cocultures. PG - 1272-8 AB - STUDY DESIGN: Experimental study of spinal cord injury using an organotypic slice culture. OBJECTIVE: To clarify the mechanism of corticospinal axon regeneration following transplantation of neural progenitor cells (NPCs) in the injured spinal cord. SUMMARY OF BACKGROUND DATA: Several mechanisms underlying central nervous system regeneration after transplantation of NPCs have been proposed; however, the precise mechanism has not been clarified. Previously, we demonstrated that transplanted NPCs secreted humoral factors that in turn promoted corticospinal axon growth using the unique organotypic coculture system involving brain cortex and spinal cord from neonatal rats. METHODS: Cultured NPCs were immunostained with antibodies against neurotrophic factors including brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-3, nerve growth factor (NGF), and ciliary neurotrophic factor (CNTF) both before and after differentiation. To evaluate corticospinal axon growth quantitatively, we used the organotypic coculture system. The dissected brain cortex and spinal cord obtained from neonatal rats were aligned next to each other and cultured on a membrane. NPCs were transplanted onto the cocultures. Furthermore, neutralizing antibodies against BDNF, NT-3, NGF, or CNTF were added to the cocultures. Axon growth from the brain cortex into the spinal cord was assessed quantitatively using anterograde axon tracing with DiI. RESULTS: The cultured NPCs were positively immunostained by antibodies against BDNF, NT3, NGF, and CTNF both before and after differentiation. Transplantation of NPCs promoted axon growth from the brain cortex into the spinal cord. The axon growth promoted by NPCs was significantly suppressed by the addition of neutralizing antibodies against BDNF, NT-3, and NGF but not CNTF. CONCLUSION: The neurotrophic factors, BDNF, NT-3, and NGF, secreted by transplanted NPCs, were involved in the promotion of corticospinal axon growth after transplantation of NPCs. FAU - Kamei, Naosuke AU - Kamei N AD - Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima City, Hiroshima, Japan. nahkamei@hiroshima-u.ac.jp FAU - Tanaka, Nobuhiro AU - Tanaka N FAU - Oishi, Yosuke AU - Oishi Y FAU - Hamasaki, Takahiko AU - Hamasaki T FAU - Nakanishi, Kazuyoshi AU - Nakanishi K FAU - Sakai, Norio AU - Sakai N FAU - Ochi, Mitsuo AU - Ochi M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Spine (Phila Pa 1976) JT - Spine JID - 7610646 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Ciliary Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Neurotrophin 3) RN - 9061-61-4 (Nerve Growth Factor) SB - IM MH - Animals MH - Animals, Genetically Modified MH - Axons/*physiology MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cell Differentiation/physiology MH - Cerebral Cortex/cytology MH - Ciliary Neurotrophic Factor/metabolism MH - Coculture Techniques MH - Embryonic Stem Cells/cytology/*metabolism MH - Female MH - Fetal Tissue Transplantation MH - Hippocampus/cytology MH - Nerve Growth Factor/metabolism MH - Nerve Growth Factors/*metabolism MH - Nerve Regeneration/*physiology MH - Neurotrophin 3/metabolism MH - Organ Culture Techniques/methods MH - Pregnancy MH - Pyramidal Tracts/*cytology/injuries MH - Rats MH - Rats, Sprague-Dawley MH - *Stem Cell Transplantation EDAT- 2007/05/23 09:00 MHDA- 2007/06/28 09:00 CRDT- 2007/05/23 09:00 PHST- 2007/05/23 09:00 [pubmed] PHST- 2007/06/28 09:00 [medline] PHST- 2007/05/23 09:00 [entrez] AID - 00007632-200705200-00004 [pii] AID - 10.1097/BRS.0b013e318059afab [doi] PST - ppublish SO - Spine (Phila Pa 1976). 2007 May 20;32(12):1272-8. doi: 10.1097/BRS.0b013e318059afab.