title: Autocrine fibronectin from differentiating mesenchymal stem cells induces the neurite elongation in vitro and promotes nerve fiber regeneration in transected spinal cord injury.
abstract: Extracellular matrix (ECM) expression is temporally and spatially regulated during the development of stem cells. We reported previously that fibronectin (FN) secreted by bone marrow mesenchymal stem cells (MSCs) was deposited on the surface of gelatin sponge (GS) soon after culture. In this study, we aimed to assess the function of accumulated FN on neuronal differentiating MSCs as induced by Schwann cells (SCs) in three dimensional transwell co-culture system. The expression pattern and amount of FN of differentiating MSCs was examined by immunofluorescence, Western blot and immunoelectron microscopy. The results showed that FN accumulated inside GS scaffold, although its mRNA expression in MSCs was progressively decreased during neural induction. MSC-derived neuron-like cells showed spindle-shaped cell body and long extending processes on FN-decorated scaffold surface. However, after blocking of FN function by application of monoclonal antibodies, neuron-like cells showed flattened cell body with short and thick neurites, together with decreased expression of integrin β1. In vivo transplantation study revealed that autocrine FN significantly facilitated endogenous nerve fiber regeneration in spinal cord transection model. Taken together, the present results showed that FN secreted by MSCs in the early stage accumulated on the GS scaffold and promoted the neurite elongation of neuronal differentiating MSCs as well as nerve fiber regeneration after spinal cord injury. This suggests that autocrine FN has a dynamic influence on MSCs in a three dimensional culture system and its potential application for treatment of traumatic spinal cord injury. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1902-1911, 2016.
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat-sen University, Ministry of Education, Guangzhou, 510080, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat-sen University, Ministry of Education, Guangzhou, 510080, China.|Department of Histology and Embryology, Guangdong Medical University, Zhanjiang, 524023, China.
authors.forename: Yuan-Huan
authors.initials: YH
authors.lastname: Ma
authors.affiliation: Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Yuan-Feng
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat-sen University, Ministry of Education, Guangzhou, 510080, China.
authors.forename: Xue-Cheng
authors.initials: XC
authors.lastname: Qiu
authors.affiliation: Department of Electron Microscope, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Jin-Lang
authors.initials: JL
authors.lastname: Wu
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore.
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat-sen University, Ministry of Education, Guangzhou, 510080, China.|Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.|Institute of Spinal Cord Injury, Sun Yat-sen University, Guangzhou, 510120, China.|Co-innovation Center of Neuroregeneration, Jiangsu, 226019, China.|Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Yuan-Shan
authors.initials: YS
authors.lastname: Zeng
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000187:drug effects; D018920:Coculture Techniques; D005260:Female; D005353:Fibronectins / Q000494:pharmacology*; D005780:Gelatin / Q000737:chemistry; D021621:Imaging, Three-Dimensional; D019012:Integrin beta1 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D009412:Nerve Fibers / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*
chemical_list: D005353:Fibronectins; D019012:Integrin beta1; D005780:Gelatin
keywords: fibronectin; gelatin sponge scaffold; mesenchymal stem cells; nerve fiber regeneration; neurite outgrowth