文献类型：期刊文献

英文题名：Decellularized extracellular matrix enriched with GDNF enhances neurogenesis and remyelination for improved motor recovery after spinal cord injury

作者：Liu, Jiashang[1];Yan, Ruijia[1];Wang, Bixue[1];Chen, Shu[1];Hong, Hua[1];Liu, Changsheng[1];Chen, Xi[1]

机构：[1]East China Univ Sci & Technol, Minist Educ, Sch Mat Sci & Engn, Engn Res Ctr Biomat,Frontiers Sci Ctr Materiobiol, Shanghai 200237, Peoples R China

年份：2024

卷号：180

起止页码：308

外文期刊名：ACTA BIOMATERIALIA

收录：;EI(收录号：20241816001881);WOS:【SCI-EXPANDED(收录号:WOS:001262051900001)】；

基金：This work was financially supported by the National Natural Science Foundation of China (Nos. 32371464 , 32101151) , Shanghai Key Laboratory of Orthopaedic Implants (KFKT202209) , National High-tech R&D Plan Project (2022YFC2403200) . We acknowledge Prof. Rongrong Zhu (Tongji University) , Prof. Wei Zhu (South China University of Technology) and Yanjie Zhu (Shanghai Tenth People's Hospital) for their helpful discussion. Any opinions, findings, con- clusions, or recommendations expressed herein are those of the author (s) .

语种：英文

外文关键词：Spinal cord injury; Decellularized; GDNF; Neurogenesis; Remyelination; Motor functional recovery

摘要：Motor functional improvement represents a paramount treatment objective in the post-spinal cord injury (SCI) recovery process. However, neuronal cell death and axonal degeneration following SCI disrupt neural signaling, impeding the motor functional recovery. In this study, we developed a multifunctional decellularized spinal cord-derived extracellular matrix (dSECM), crosslinked with glial cell-derived neurotrophic factor (GDNF), to promote differentiation of stem cells into neural-like cells and facilitate axonogenesis and remyelination. After decellularization, the immunogenic cellular components were effectively removed in dSECM, while the crucial protein components were retained which supports stem cells proliferation and differentiation. Furthermore, sustained release of GDNF from the dSECM facilitated axonogenesis and remyelination by activating the PI3K/Akt and MEK/Erk pathways. Our findings demonstrate that the dSECM-GDNF platform promotes neurogenesis, axonogenesis, and remyelination to enhance neural signaling, thereby yielding promising therapeutic effects for motor functional improvement after SCI. Statement of significance The dSECM promotes the proliferation and differentiation of MSCs or NSCs by retaining proteins associated with positive regulation of neurogenesis and neuronal differentiation, while eliminating proteins related to negative regulation of neurogenesis. After crosslinking, GDNF can be gradually released from the platform, thereby promoting neural differentiation, axonogenesis, and remyelination to enhance neural signaling through activation of the PI3K/Akt and MEK/Erk pathways. In vivo experiments demonstrated that dSECM-GDNF/MSC@GelMA hydrogel exhibited the ability to facilitate neuronal regeneration at 4 weeks post-surgery, while promoting axonogenesis and remyelination at 8 weeks post-surgery, ultimately leading to enhanced motor functional recovery. This study elucidates the ability of neural regeneration strategy to promote motor functional recovery and provides a promising approach for designing multifunctional tissue for SCI treatment. (c) 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.