Axon guidance gene-targeted siRNA delivery system improves neural stem cell transplantation therapy after spinal cord injury

Biomaterials Research

Research Article

Seung Hun Sheen¹  Wan-Kyu Ko²  Seil Sohn²  Daye Lee²  Seong Jun Kim²  Gong Ho Han²  Min Jai Cho³ 

[1] Department of Neurosurgery, CHA Bundang Medical Center, CHA University, 59, Yatap-ro, Bundang- gu, 13496, Seongnam-si, Gyeonggi-do, Republic of Korea;Department of Neurosurgery, CHA Bundang Medical Center, CHA University, 59, Yatap-ro, Bundang- gu, 13496, Seongnam-si, Gyeonggi-do, Republic of Korea;Department of Biomedical Science, CHA University, 335, Pangyo-ro, Bundang-gu, 13488, Seongnam-si, Gyeonggi-do, Republic of Korea;Department of Neurosurgery, Chungbuk National University, 776, 1Sunhawn-ro, Seowon-gu, 28644, Cheongju-si, Republic of Korea;

关键词: Spinal cord injuries;    Neural stem cells;    Semaphorin-3A;    Small interfering RNA;    Axon guidance;   

DOI  :  10.1186/s40824-023-00434-2

 received in 2023-06-16, accepted in 2023-09-18,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundNeural stem cells (NSCs) derived from the embryonic spinal cord are excellent candidates for the cellular regeneration of lost neural cells after spinal cord injury (SCI). Semaphorin 3 A (Sema3A) is well known as being implicated in the major axon guidance of the growth cone as a repulsive function during the development of the central nervous system, yet its function in NSC transplantation therapy for SCI has not been investigated. Here, we report for the first time that embryonic spinal cord-derived NSCs significantly express Sema3A in the SCI environment, potentially facilitating inhibition of cell proliferation after transplantation.MethodssiRNA-Sema3A was conjugated with poly-l-lysin-coated gold nanoparticles (AuNPs) through a charge interaction process. NSCs were isolated from embryonic spinal cords of rats. Then, the cells were embedded into a dual-degradable hydrogel with the siRNA- Sema3A loaded-AuNPs and transplanted after complete SCI in rats.ResultsThe knockdown of Sema3A by delivering siRNA nanoparticles via dual-degradable hydrogels led to a significant increase in cell survival and neuronal differentiation of the transplanted NSCs after SCI. Of note, the knockdown of Sema3A increased the synaptic connectivity of transplanted NSC in the injured spinal cord. Moreover, extracellular matrix molecule and functional recovery were significantly improved in Sema3A-inhibited rats compared to those in rats with only NSCs transplanted.ConclusionsThese findings demonstrate the important role of Sema3A in NSC transplantation therapy, which may be considered as a future cell transplantation therapy for SCI cases.Graphical Abstract

【 授权许可】

CC BY   
© The Korean Society for Biomaterials 2023

【 图 表 】

12951_2015_155_Article_IEq18.gif

Fig. 7

Fig. 2

Fig. 2

Fig. 1

Fig. 6

12888_2023_5299_Article_IEq3.gif

12888_2023_5299_Article_IEq1.gif