PMID- 19411199 OWN - NLM STAT- MEDLINE DCOM- 20130912 LR - 20220318 IS - 1876-7753 (Electronic) IS - 1873-5061 (Linking) VI - 3 IP - 1 DP - 2009 Jul TI - Human bone marrow-derived mesenchymal stem cells secrete brain-derived neurotrophic factor which promotes neuronal survival in vitro. PG - 63-70 LID - 10.1016/j.scr.2009.02.006 [doi] AB - Bone marrow-derived mesenchymal stem cells (MSCs) are of therapeutic interest in a variety of neurological diseases. In this study, we wished to determine whether human MSCs secrete factors which protect cultured rodent cortical neurons from death by trophic factor withdrawal or nitric oxide (NO) exposure. Medium conditioned by MSCs attenuated neuronal death under these conditions, a process which was dependent on intact PI(3)kinase/Akt pathway signaling. Trophic withdrawal and NO exposure in cultured cortical neurons led to reduction in Akt signaling pathways, whereas NO administration activated p38 MAPkinase in neuronal cultures. Addition of MSC-conditioned medium significantly activated the PI3kinase/Akt pathway and in neurons exposed to NO, MSC-conditioned medium reduced p38 signaling. We show that MSCs secrete brain-derived neurotrophic factor (BDNF) and addition of anti-BDNF neutralising antibodies to MSC-conditioned medium attenuated its neuroprotective effect. Exposure of neurons to BDNF increased activation of Akt pathways and protected neurons from trophic factor withdrawal. These observations determine the mechanisms of neuroprotection offered by MSC-derived factors and suggest an important role for BDNF in neuronal protection. FAU - Wilkins, Alastair AU - Wilkins A AD - Department of Neurology, Institute of Clinical Neurosciences, Clinical Sciences North Bristol, University of Bristol, Bristol BS16 1LE, UK. alastair.wilkins@bristol.ac.uk FAU - Kemp, Kevin AU - Kemp K FAU - Ginty, Mark AU - Ginty M FAU - Hares, Kelly AU - Hares K FAU - Mallam, Elizabeth AU - Mallam E FAU - Scolding, Neil AU - Scolding N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090327 PL - England TA - Stem Cell Res JT - Stem cell research JID - 101316957 RN - 0 (Antibodies) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Culture Media, Conditioned) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Antibodies/immunology MH - Apoptosis/drug effects MH - Bone Marrow Cells/*cytology MH - Brain-Derived Neurotrophic Factor/immunology/*metabolism MH - Cells, Cultured MH - Culture Media, Conditioned/pharmacology MH - Humans MH - Mesenchymal Stem Cells/cytology/*metabolism MH - Neurons/*cytology/drug effects MH - Nitric Oxide/toxicity MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats MH - Signal Transduction MH - p38 Mitogen-Activated Protein Kinases/metabolism EDAT- 2009/05/05 09:00 MHDA- 2013/09/13 06:00 CRDT- 2009/05/05 09:00 PHST- 2008/10/02 00:00 [received] PHST- 2008/12/03 00:00 [revised] PHST- 2009/02/25 00:00 [accepted] PHST- 2009/05/05 09:00 [entrez] PHST- 2009/05/05 09:00 [pubmed] PHST- 2013/09/13 06:00 [medline] AID - S1873-5061(09)00028-2 [pii] AID - 10.1016/j.scr.2009.02.006 [doi] PST - ppublish SO - Stem Cell Res. 2009 Jul;3(1):63-70. doi: 10.1016/j.scr.2009.02.006. Epub 2009 Mar 27.