Kim Seong Jun, Ko Wan-Kyu, Han Gong Ho, Lee Daye, Cho Min Jai, Sheen Seung Hun, Sohn Seil
Department of Neurosurgery, CHA Bundang Medical Center, CHA University, 59, Yatap-ro, Bundang- gu, Seongnam-si, 13496, Gyeonggi-do, Republic of Korea.
Department of Biomedical Science, CHA University, 335, Pangyo-ro, Bundang-gu, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea.
Biomater Res. 2023 Oct 15;27(1):101. doi: 10.1186/s40824-023-00434-2.
Neural 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.
siRNA-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.
The 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.
These findings demonstrate the important role of Sema3A in NSC transplantation therapy, which may be considered as a future cell transplantation therapy for SCI cases.
源自胚胎脊髓的神经干细胞（NSCs）是脊髓损伤（SCI）后丢失神经细胞进行细胞再生的理想候选者。信号素3A（Sema3A）作为中枢神经系统发育过程中生长锥主要轴突导向的排斥因子而广为人知，但其在NSC移植治疗SCI中的作用尚未得到研究。在此，我们首次报道胚胎脊髓来源的NSCs在SCI环境中显著表达Sema3A，这可能会促进移植后细胞增殖的抑制。
通过电荷相互作用过程将siRNA-Sema3A与聚L-赖氨酸包被的金纳米颗粒（AuNPs）偶联。从大鼠胚胎脊髓中分离出NSCs。然后，将细胞包埋在载有siRNA-Sema3A的AuNPs的双可降解水凝胶中，并在大鼠完全性SCI后进行移植。
通过双可降解水凝胶递送siRNA纳米颗粒敲低Sema3A，导致SCI后移植的NSCs的细胞存活率和神经元分化显著增加。值得注意的是，Sema3A的敲低增加了移植的NSC在损伤脊髓中的突触连接。此外，与仅移植NSCs的大鼠相比，Sema3A抑制的大鼠的细胞外基质分子和功能恢复得到显著改善。
这些发现证明了Sema3A在NSC移植治疗中的重要作用，这可能被视为未来SCI病例的细胞移植治疗方法。
