title: Enhanced neuroprotection with decellularized brain extracellular matrix containing bFGF after intracerebral transplantation in Parkinson's disease rat model.
abstract: Extracellular matrix-based biomaterials have many advantages over synthetic polymer materials for regenerative medicine applications. In central nervous system (CNS), basic fibroblast growth factor (bFGF) is widely studied as a potential agent for Parkinson's disease (PD). However, the poor stability of bFGF hampered its clinical use. In this study, CNS-derived biologic scaffold containing bFGF was used to enhance and extend the neuroprotective effect of bFGF on PD targeted therapy. Decellularized brain extracellular matrix (dcBECM) was prepared by chemical extraction. The biocompatibility of dcBECM was evaluated using CCK-8 assay and magnetic resonance imaging (MRI). The controlled-release behavior of dcBECM containing bFGF (bFGF+dcBECM) was confirmed by ELISA assay. Furthermore, the cytocompatibility and neuroprotective effect of bFGF+dcBECM was evaluated in vitro and in vivo. From results, dcBECM showed a three-dimensional network structure with high biocompatibility. MRI of dcBECM implanted rats showed nearly seamless fusion of dcBECM with the adjoining tissues. The cumulative release rate of bFGF+dcBECM in vitro reached to 75.88% at 10h and maintained sustained release trend during the observation. ELISA results in vivo further confirmed the sustained-release behavior (from 12h to 3d) of bFGF+dcBECM in brain tissues. Among the experimental groups, bFGF+dcBECM group showed the highest cell survival rate of PD model cells, improved behavioral recovery and positive expressions of neurotrophic proteins in PD recovered rats. In conclusion, sustained neuroprotection in PD rats was achieved by using bFGF+dcBECM. The combination of dcBECM and bFGF would be a promising therapeutic strategy to realize an effective and safe alternative for CNS disease treatment.
authors.affiliation: College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China; The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China; Departments of Pharmacology and toxicology, University of Louisville School of Medicine, Louisville, 40202, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Lin
authors.affiliation: School of Pharmacy, Temple University, Philadelphia, PA 19140, USA.
authors.forename: Ho Lun
authors.initials: HL
authors.lastname: Wong
authors.affiliation: College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China.
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Tian
authors.affiliation: Biopharmaceutical R&D Center of Jinan University, Guangzhou, Guangdong Province 510000, China.
authors.forename: Ya-Dong
authors.initials: YD
authors.lastname: Huang
authors.affiliation: College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China.
authors.forename: Pian-Pian
authors.initials: PP
authors.lastname: Chen
authors.affiliation: College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China.
authors.forename: Zi-Liang
authors.initials: ZL
authors.lastname: Fan
authors.affiliation: The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China. Electronic address: lctuua@sina.com.
authors.forename: Cui-Tao
authors.initials: CT
authors.lastname: Lu
authors.affiliation: College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China; The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, 325000, China. Electronic address: zoelinqian@126.com.
authors.forename: Ying-Zheng
authors.initials: YZ
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000601:surgery* / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D065546:Drug Liberation; D005109:Extracellular Matrix / Q000637:transplantation*; D016222:Fibroblast Growth Factor 2 / Q000493:pharmacokinetics / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008422:Materials Testing; D009414:Nerve Growth Factors / Q000378:metabolism; D059906:Neuroimaging; D000066829:Neuroprotection; D010300:Parkinson Disease / Q000601:surgery*; D051381:Rats; D014180:Transplantation / Q000379:methods*
chemical_list: D009414:Nerve Growth Factors; D016222:Fibroblast Growth Factor 2
keywords: Basic fibroblast growth factor; Decellularized brain extracellular matrix; Neuroprotection; Parkinson’s disease; Transplantation