Enhanced neuroprotection with decellularized brain extracellular matrix containing bFGF after intracerebral transplantation in Parkinson’s disease rat model

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• 作者：Qian Lin^a ; ^b ; ^c ; ¹ ; Ho Lun Wong^d ; ¹ ; Fu-Rong Tian^a ; ¹ ; Ya-Dong Huang^e ; Jie Xu^a ; Jing-Jing Yang^a ; Pian-Pian Chen^a ; Zi-Liang Fan^a ; Cui-Tao Lu^b ; ^{lctuua@sina.com} ; Ying-Zheng Zhao^a ; ^b ; ^{zoelinqian@126.com}
• 关键词：Decellularized brain extracellular matrix ; Basic fibroblast growth factor ; Parkinson&rsquo ; s disease ; Neuroprotection ; Transplantation
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：30 January 2017
• 年：2017
• 卷：517
• 期：1-2
• 页码：383-394
• 全文大小：4366 K
• 卷排序：517

文摘

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 10 h and maintained sustained release trend during the observation. ELISA results in vivo further confirmed the sustained-release behavior (from 12 h 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.