PMID- 24124760 OWN - NLM STAT- MEDLINE DCOM- 20141117 LR - 20220310 IS - 1557-8534 (Electronic) IS - 1547-3287 (Linking) VI - 23 IP - 7 DP - 2014 Apr 1 TI - Stimulating the neurotrophic and angiogenic properties of human adipose-derived stem cells enhances nerve repair. PG - 741-54 LID - 10.1089/scd.2013.0396 [doi] AB - In future, adipose-derived stem cells (ASC) might be used to treat neurological disorders. In this study, the neurotrophic and angiogenic properties of human ASC were evaluated, and their effects in a peripheral nerve injury model were determined. In vitro growth factor stimulation of the cells resulted in increased secretion of brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), vascular endothelial growth factor-A (VEGF-A), and angiopoietin-1 proteins. Conditioned medium from stimulated cells increased neurite outgrowth of dorsal root ganglia (DRG) neurons. Similarly, stimulated cells showed an enhanced ability to induce capillary-like tube formation in an in vitro angiogenesis assay. ASC were seeded into a fibrin conduit that was used to bridge a 10 mm rat nerve gap. After 2 weeks, the animals treated with control or stimulated ASC showed an enhanced axon regeneration distance. Stimulated cells evoked more total axon growth. Analysis of regeneration and apoptosis-related gene expression showed that both ASC and stimulated ASC enhanced GAP-43 and activating transcription factor 3 (ATF-3) expression in the spinal cord and reduced c-jun expression in the DRG. Caspase-3 expression in the DRG was reduced by stimulated ASC. Both ASC and stimulated ASC also increased the vascularity of the fibrin nerve conduits. Thus, ASC produce functional neurotrophic and angiogenic factors, creating a more desirable microenvironment for nerve regeneration. FAU - Kingham, Paul J AU - Kingham PJ AD - 1 Section for Anatomy, Department of Integrative Medical Biology, Umea University , Umea, Sweden . FAU - Kolar, Mallappa K AU - Kolar MK FAU - Novikova, Liudmila N AU - Novikova LN FAU - Novikov, Lev N AU - Novikov LN FAU - Wiberg, Mikael AU - Wiberg M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131122 PL - United States TA - Stem Cells Dev JT - Stem cells and development JID - 101197107 RN - 0 (Activating Transcription Factor 3) RN - 0 (Angiopoietin-1) RN - 0 (Angpt1 protein, rat) RN - 0 (Atf3 protein, rat) RN - 0 (Biomarkers) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Culture Media, Conditioned) RN - 0 (GAP-43 Protein) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (vascular endothelial growth factor A, rat) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) SB - IM MH - Activating Transcription Factor 3/genetics/metabolism MH - Adipocytes/*cytology/metabolism/transplantation MH - Adipose Tissue/*cytology/drug effects/metabolism MH - Adult MH - Angiopoietin-1/genetics/metabolism MH - Animals MH - Biomarkers/metabolism MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Cell Differentiation MH - Cell Lineage/physiology MH - Culture Media, Conditioned/pharmacology MH - GAP-43 Protein/genetics/metabolism MH - Ganglia, Spinal/cytology/metabolism MH - Gene Expression MH - Glial Cell Line-Derived Neurotrophic Factor/genetics/metabolism MH - Humans MH - JNK Mitogen-Activated Protein Kinases/genetics/metabolism MH - Mesenchymal Stem Cells/*cytology/drug effects/metabolism MH - Neovascularization, Physiologic MH - Nerve Regeneration/*physiology MH - Neurons/*cytology/metabolism MH - Rats MH - Spinal Cord/cytology/metabolism MH - Stem Cell Transplantation MH - Vascular Endothelial Growth Factor A/genetics/metabolism EDAT- 2013/10/16 06:00 MHDA- 2014/11/18 06:00 CRDT- 2013/10/16 06:00 PHST- 2013/10/16 06:00 [entrez] PHST- 2013/10/16 06:00 [pubmed] PHST- 2014/11/18 06:00 [medline] AID - 10.1089/scd.2013.0396 [doi] PST - ppublish SO - Stem Cells Dev. 2014 Apr 1;23(7):741-54. doi: 10.1089/scd.2013.0396. Epub 2013 Nov 22.