PMID- 25316594 OWN - NLM STAT- MEDLINE DCOM- 20151215 LR - 20181202 IS - 1937-335X (Electronic) IS - 1937-3341 (Linking) VI - 21 IP - 5-6 DP - 2015 Mar TI - Effect of brain-derived neurotrophic factor on mesenchymal stem cell-seeded electrospinning biomaterial for treating ischemic diabetic ulcers via milieu-dependent differentiation mechanism. PG - 928-38 LID - 10.1089/ten.TEA.2014.0113 [doi] AB - Great challenges in transplantation of mesenchymal stem cells (MSCs) for treating ischemic diabetic ulcers (IDUs) are to find a suitable carrier and create a beneficial microenvironment. Brain-derived neurotrophic factor (BDNF), a member of neurotrophin family, is considered angiogenic and neuroprotective. Given that IDUs are caused by vascular disease and peripheral neuropathy, we used BDNF as a stimulant, and intended to explore the role of new biomaterials complex with MSCs in wound healing. BDNF promoted the proliferation and migration of MSCs using MTT, transwell, and cell scratch assays. The activity of human umbilical vein endothelial cells (HUVECs) was also enhanced by the MSC-conditioned medium in the presence of BDNF, via a vascular endothelial growth factor-independent pathway. Since proliferated HUVECs in the BDNF group made the microenvironment more conducive to endothelial differentiation of MSCs, by establishing co-culture systems with the two cell types, endothelial cells derived from MSCs increased significantly. A new biomaterial made of polylactic acid, silk and collagen was used as the carrier dressing. After transplantation of the BDNF-stimulated MSC/biomaterial complex, the ulcers in hindlimb ischemic mice healed prominently. More blood vessel formation was observed in the wound tissue, and more MSCs were co-stained with some endothelial-specific markers such as cluster of differentiation (CD)31 and von Willebrand Factor (vWF) in the treatment group than in the control group. These results demonstrated that BDNF could improve microenvironment in the new biomaterial, and induce MSCs to differentiate into endothelial cells indirectly, thus accelerating ischemic ulcer healing. FAU - He, Siyi AU - He S AD - 1 Department of Anatomy, National and Regional Engineering Laboratory of Tissue Engineering, Key Lab for Biomechanics of Chongqing, Third Military Medical University , Chongqing, China . FAU - Shen, Lei AU - Shen L FAU - Wu, Yangxiao AU - Wu Y FAU - Li, Li AU - Li L FAU - Chen, Wen AU - Chen W FAU - Hou, Chunli AU - Hou C FAU - Yang, Mingcan AU - Yang M FAU - Zeng, Wen AU - Zeng W FAU - Zhu, Chuhong AU - Zhu C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141211 PL - United States TA - Tissue Eng Part A JT - Tissue engineering. Part A JID - 101466659 RN - 0 (Biocompatible Materials) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Culture Media, Conditioned) RN - 0 (Cytokines) RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Biocompatible Materials/pharmacology/*therapeutic use MH - Brain-Derived Neurotrophic Factor/pharmacology/*therapeutic use MH - Cell Differentiation/*drug effects MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Cellular Microenvironment/*drug effects MH - Collagen/pharmacology MH - Culture Media, Conditioned/pharmacology MH - Cytokines/metabolism MH - Diabetic Foot/*drug therapy/pathology/physiopathology MH - Hindlimb/blood supply/pathology MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Ischemia/drug therapy/pathology/physiopathology MH - Male MH - Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*cytology/drug effects MH - Mice, Inbred C57BL MH - Neovascularization, Physiologic/drug effects MH - Wound Healing/drug effects EDAT- 2014/10/16 06:00 MHDA- 2015/12/17 06:00 CRDT- 2014/10/16 06:00 PHST- 2014/10/16 06:00 [entrez] PHST- 2014/10/16 06:00 [pubmed] PHST- 2015/12/17 06:00 [medline] AID - 10.1089/ten.TEA.2014.0113 [doi] PST - ppublish SO - Tissue Eng Part A. 2015 Mar;21(5-6):928-38. doi: 10.1089/ten.TEA.2014.0113. Epub 2014 Dec 11.