PMID- 25193075 OWN - NLM STAT- MEDLINE DCOM- 20150326 LR - 20201023 IS - 1090-2422 (Electronic) IS - 0014-4827 (Linking) VI - 331 IP - 1 DP - 2015 Feb 1 TI - Intrinsic mechanisms underlying the neurotrophic activity of adipose derived stem cells. PG - 142-151 LID - S0014-4827(14)00372-3 [pii] LID - 10.1016/j.yexcr.2014.08.034 [doi] AB - Adipose derived stem cells (ADSC) can be differentiated into Schwann cell-like cells which enhance nerve function and regeneration. However, the signalling mechanisms underlying the neurotrophic potential of ADSC remain largely unknown. In this study, we hypothesised that ADSC, upon stimulation with a combination of growth factors, could rapidly produce brain derived neurotrophic factor (BDNF) with a similar molecular mechanism to that functioning in the nervous system. Within 48 h of stimulation, ADSC demonstrated potent neurotrophic effects on dorsal root ganglion neurons, at a magnitude equivalent to that of the longer term differentiated Schwann cell-like cells. Stimulated ADSC showed rapid up-regulation of the neuronal activity dependent promoter BDNF exon IV along with an augmented expression of full length protein encoding BDNF exon IX. BDNF protein was secreted at a concentration similar to that produced by differentiated Schwann cell-like cells. Stimulation also activated the BDNF expression gating transcription factor, cAMP responsive element binding (CREB) protein. However, blocking phosphorylation of CREB with the protein kinase A small molecule inhibitor H89 did not suppress secretion of BDNF protein. These results suggest rapid BDNF production in ADSC is mediated through multiple compensatory pathways independent of, or in addition to, the CREB neuronal activation cascade. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Tse, Kai-Hei AU - Tse KH AD - Department of Integrative Medical Biology, Section of Anatomy, Umea University, SE-901 87 Umea, Sweden. FAU - Novikov, Lev N AU - Novikov LN AD - Department of Integrative Medical Biology, Section of Anatomy, Umea University, SE-901 87 Umea, Sweden. FAU - Wiberg, Mikael AU - Wiberg M AD - Department of Integrative Medical Biology, Section of Anatomy, Umea University, SE-901 87 Umea, Sweden; Department of Surgical and Perioperative Sciences, Section of Hand & Plastic Surgery, Umea University, Sweden. FAU - Kingham, Paul J AU - Kingham PJ AD - Department of Integrative Medical Biology, Section of Anatomy, Umea University, SE-901 87 Umea, Sweden. Electronic address: paul.kingham@umu.se. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140901 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (RNA, Messenger) RN - SY7Q814VUP (Calcium) SB - IM MH - Adipocytes/cytology/*metabolism MH - Animals MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Calcium/metabolism MH - *Cell Differentiation MH - Cell Proliferation MH - Cells, Cultured MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Ganglia, Spinal/cytology/*metabolism MH - Immunoenzyme Techniques MH - Nerve Growth Factors/genetics/metabolism MH - Neurites/*metabolism MH - Neurons/cytology/*metabolism MH - Phenotype MH - Phosphorylation MH - RNA, Messenger/genetics MH - Rats MH - Rats, Inbred F344 MH - Rats, Sprague-Dawley MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction MH - Schwann Cells/cytology/*metabolism MH - Signal Transduction MH - Stem Cells/cytology/*metabolism OTO - NOTNLM OT - Brain derived neurotrophic factor OT - Differentiation OT - Neurite OT - Regeneration OT - Stem cells EDAT- 2014/09/07 06:00 MHDA- 2015/03/27 06:00 CRDT- 2014/09/07 06:00 PHST- 2014/07/20 00:00 [received] PHST- 2014/08/24 00:00 [accepted] PHST- 2014/09/07 06:00 [entrez] PHST- 2014/09/07 06:00 [pubmed] PHST- 2015/03/27 06:00 [medline] AID - S0014-4827(14)00372-3 [pii] AID - 10.1016/j.yexcr.2014.08.034 [doi] PST - ppublish SO - Exp Cell Res. 2015 Feb 1;331(1):142-151. doi: 10.1016/j.yexcr.2014.08.034. Epub 2014 Sep 1.