PMID- 28642578 OWN - NLM STAT- MEDLINE DCOM- 20181231 LR - 20181231 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 IP - 1 DP - 2017 Jun 22 TI - Human endothelial cells secrete neurotropic factors to direct axonal growth of peripheral nerves. PG - 4092 LID - 10.1038/s41598-017-04460-8 [doi] LID - 4092 AB - Understanding how nerves spontaneously innervate tissues or regenerate small injuries is critical to enhance material-based interventions to regenerate large scale, traumatic injuries. During embryogenesis, neural and vascular tissues form interconnected, complex networks as a result of signaling between these tissue types. Here, we report that human endothelial cells (HUVECs) secrete brain-derived neurotrophic factor (BDNF), which significantly stimulated axonal growth from chicken or rat dorsal root ganglia (DRGs). HUVEC-conditioned medium was sufficient to enhance axonal growth, demonstrating that direct cell-cell contact was not required. When BDNF was neutralized, there was a significant reduction in axonal growth when incubated in HUVEC-conditioned medium and in direct co-culture with HUVECs. These data show that HUVECs secrete neurotrophic factors that significantly enhance axonal growth, and can inform future in vivo studies to direct or pattern the angiogenic response in regenerating tissues to encourage re-innervation. FAU - Grasman, Jonathan M AU - Grasman JM AUID- ORCID: 0000-0001-8289-9627 AD - Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA. FAU - Kaplan, David L AU - Kaplan DL AD - Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA. david.kaplan@tufts.edu. LA - eng GR - F32 DE026058/DE/NIDCR NIH HHS/United States GR - P41 EB002520/EB/NIBIB NIH HHS/United States GR - R01 AR055993/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20170622 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Cytokines) RN - 0 (Nerve Growth Factors) SB - IM MH - Animals MH - Axons/*metabolism MH - Cytokines/biosynthesis/pharmacology MH - Endothelial Cells/*metabolism MH - Ganglia, Spinal/growth & development/metabolism MH - Human Umbilical Vein Endothelial Cells/metabolism MH - Humans MH - Nerve Growth Factors/*biosynthesis/pharmacology MH - *Neurogenesis/drug effects MH - Peripheral Nerves/*growth & development/*metabolism PMC - PMC5481420 COIS- The authors declare that they have no competing interests. EDAT- 2017/06/24 06:00 MHDA- 2019/01/01 06:00 PMCR- 2017/06/22 CRDT- 2017/06/24 06:00 PHST- 2016/12/06 00:00 [received] PHST- 2017/05/16 00:00 [accepted] PHST- 2017/06/24 06:00 [entrez] PHST- 2017/06/24 06:00 [pubmed] PHST- 2019/01/01 06:00 [medline] PHST- 2017/06/22 00:00 [pmc-release] AID - 10.1038/s41598-017-04460-8 [pii] AID - 4460 [pii] AID - 10.1038/s41598-017-04460-8 [doi] PST - epublish SO - Sci Rep. 2017 Jun 22;7(1):4092. doi: 10.1038/s41598-017-04460-8.