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Biological characteristics of tissue engineered-nerve grafts enhancing peripheral nerve regeneration

作者:Xiangling Li, Hang Xu, Chaochao Li, Yanjun Guan, Yu‐Li Liu, Tieyuan Zhang, Fanqi Meng, Haofeng Cheng, Xiangyu Song, Zhibo Jia, Ruichao He, Jinjuan Zhao, Shengfeng Chen, Congcong Guan, Yan Shi, Jinpeng Wang, Yu Wei, Jian Zhang, Jinshu Tang, Jiang Peng, Yu Wang · 发表于:Stem Cell Research & Therapy · 年份:2024 · DOI:10.1186/s13287-024-03827-9 · 被引用次数:29 · 研究领域:Nerve injury and regeneration、Mesenchymal stem cell research、Spine and Intervertebral Disc Pathology

BACKGROUND: A favorable regenerative microenvironment is essential for peripheral nerve regeneration. Neural tissue-specific extracellular matrix (ECM) is a natural material that helps direct cell behavior and promote axon regeneration. Both bone marrow-derived mesenchymal stem cells (BMSCs) and adipose-derived mesenchymal stem cells (ADSCs) transplantation are effective in repairing peripheral nerve injury (PNI). However, there is no study that characterizes the in vivo microenvironmental characteristics of these two MSCs for the early repair of PNI when combined with neural tissue-derived ECM materials, i.e., acellular nerve allograft (ANA). METHODS: In order to investigate biological characteristics, molecular mechanisms of early stage, and effectiveness of ADSCs- or BMSCs-injected into ANA for repairing PNI in vivo, a rat 10 mm long sciatic nerve defect model was used. We isolated primary BMSCs and ADSCs from bone marrow and adipose tissue, respectively. First, to investigate the in vivo response characteristics and underlying molecular mechanisms of ANA combined with BMSCs or ADSCs, eighty-four rats were randomly divided into three groups: ANA group, ANA+BMSC group, and ANA+ADSC group. We performed flow cytometry, RT-PCR, and immunofluorescence staining up to 4 weeks postoperatively. To further elucidate the underlying molecular mechanisms, changes in long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) were systematical...