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Publications

Journal Article Epublish

PubMed: 40275960 DOI: 10.1016/j.mtbio.2025.101753

DON-Apt19S bioactive scaffold transplantation promotes spinal cord repair in rats with transected spinal cord injury by effectively recruiting endogenous neural stem cells and mesenchymal stem cells.

Mater Today Bio 32:101753

Authors: Bi-Qin Lai, Rong-Jie Wu, Chuang-Ran Wu, Hai-Yang Yu, Jing Xu, Shang-Bin Yang, Zheng-Hong Chen, Xing Li, Yi-Nan Guo, Yue Yang, Ming-Tian Che, Ting-Ting Wu, Guang-Tao Fu, Yu-Hui Yang, Zhen Chen, Nan Hua, Rui Liu, Qiu-Jian Zheng, Yuan-Feng Chen

Affiliations

  • 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. Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China. Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. Institute of Spinal Cord Injury, Sun Yat-sen University, Guangzhou, China.
  • Department of Orthopedics, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
  • Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat-sen University, Ministry of Education, Guangzhou, China.
  • Shantou University Medical College, Shantou, China.
  • Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat-sen University, Ministry of Education, Guangzhou, China. Rehabilitation Medicine Department, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
  • State Key Laboratory of Dampness Syndrome of Chinese Medicine, Department of Orthopedic Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • Cedars Sinai Biobank & Research Pathology Resource, Cedars-Sinai, Los Angeles, CA, 90048, USA.
  • National Engineering Research Center for Healthcare Devices, Guangdong Key Lab of Medical Electronic Instruments and Polymer Material Products, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou, China.
  • Department of Orthopedics, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.

Abstract

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.

MeSH

Cells, Genes, Neural Stem Cells, Spinal Cord, Microscopy, Electron, Scanning Transmission, Spinal Cord Injuries, Stem Cells, Mesenchymal Stem Cells, Spinal Cord Regeneration, Transplantation, Spine