title: Stimulating the neurotrophic and angiogenic properties of human adipose-derived stem cells enhances nerve repair.
abstract: 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.
authors.affiliation: 1 Section for Anatomy, Department of Integrative Medical Biology, Umeå University , Umeå, Sweden .
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kingham
authors.forename: Mallappa K
authors.initials: MK
authors.lastname: Kolar
authors.forename: Liudmila N
authors.initials: LN
authors.lastname: Novikova
authors.forename: Lev N
authors.initials: LN
authors.lastname: Novikov
authors.forename: Mikael
authors.initials: M
authors.lastname: Wiberg
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage / Q000502:physiology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D033581:Stem Cell Transplantation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D051700:Activating Transcription Factor 3; D042683:Angiopoietin-1; C467629:Angpt1 protein, rat; C497108:Atf3 protein, rat; D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D017077:Culture Media, Conditioned; D019922:GAP-43 Protein; D051100:Glial Cell Line-Derived Neurotrophic Factor; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D048031:JNK Mitogen-Activated Protein Kinases