Lai Bi-Qin, Wu Rong-Jie, Wu Chuang-Ran, Yu Hai-Yang, Xu Jing, Yang Shang-Bin, Chen Zheng-Hong, Li Xing, Guo Yi-Nan, Yang Yue, Che Ming-Tian, Wu Ting-Ting, Fu Guang-Tao, Yang Yu-Hui, Chen Zhen, Hua Nan, Liu Rui, Zheng Qiu-Jian, Chen Yuan-Feng
Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat-sen University, Ministry of Education, Guangzhou, China.
Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Mater Today Bio. 2025 Apr 10;32:101753. doi: 10.1016/j.mtbio.2025.101753. eCollection 2025 Jun.
The spinal cord's limited regeneration is attributed to the scarcity of endogenous stem cells and a poor post-injury microenvironment in adult mammals. To overcome these challenges, we transplanted a DNA aptamer 19S (Apt19S) sustained-release decellularized optic nerve (DON) scaffold (DON-A) into completely transected spinal cord injury (SCI) site in rats and investigated its effect on endogenous stem cell recruitment and differentiation, which subsequently contributed to SCI repair. It has been demonstrated that Apt19S specifically binds to the membrane receptor alkaline phosphatase highly expressed on neural stem cells (NSCs) and mesenchymal stem cells (MSCs), and our study further proved that Apt19S can simultaneously recruit endogenous NSCs and MSCs to the lesion of SCI. In our study, the DON-A promoted stem cell proliferation in the early stage of the injury, followed by the rapid neurogenesis through NSCs and revascularization via MSCs. Synaptic connections between corticospinal tracts and calcitonin gene-related peptide positive nerve fibers with newborn neurons confirmed the formation of endogenous neuronal relays at the injury site, which improved the rats' motor and sensory functions. This study offers a new strategy for recruiting both NSCs and MSCs to synergistically overcome low spinal cord self-repair ability, holding a high potential for clinical translation.
成年哺乳动物脊髓再生能力有限，这归因于内源性干细胞的稀缺以及损伤后恶劣的微环境。为克服这些挑战，我们将一种DNA适配体19S（Apt19S）缓释脱细胞视神经（DON）支架（DON-A）移植到大鼠完全横断性脊髓损伤（SCI）部位，并研究其对内源性干细胞募集和分化的影响，这随后有助于脊髓损伤修复。已证明Apt19S能特异性结合在神经干细胞（NSCs）和间充质干细胞（MSCs）上高表达的膜受体碱性磷酸酶，我们的研究进一步证明Apt19S能同时将内源性NSCs和MSCs募集到脊髓损伤部位。在我们的研究中，DON-A在损伤早期促进干细胞增殖，随后通过NSCs实现快速神经发生，并通过MSCs实现血管再生。皮质脊髓束与新生神经元之间的突触连接以及降钙素基因相关肽阳性神经纤维证实了损伤部位内源性神经中继的形成，这改善了大鼠的运动和感觉功能。本研究为募集NSCs和MSCs协同克服脊髓自身修复能力低下提供了一种新策略，具有很高的临床转化潜力。
