LONG-TERM EVALUATION OF THE SAFETY AND EFFECTIVENESS OF NEURAL STEM CELL TRANSPLANTATION FOR CHRONIC THORACIC SPINAL CORD INJURY
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Spinal cord injury (SCI) is a debilitating neurological condition that leads to partial or complete loss of motor and sensory function, depending on the injury’s severity and location. Conventional therapies focus on surgical stabilization, prevention of secondary damage, and rehabilitation. However, these approaches often fall short in restoring long-term functionality. In recent years, cell-based therapies have emerged as promising alternatives, particularly those involving neural stem cells (NSCs). This literature review explores the long-term safety and effectiveness of NSC transplantation for chronic thoracic SCI, based on studies published between 2010 and 2025. Research shows that fetal-derived NSCs, such as HuCNS-SC, demonstrate a high safety profile and low risk of tumor formation due to their committed neural lineage. Clinical trials report early signs of motor improvement and reduced spasticity in chronic SCI patients following transplantation. Additionally, mesenchymal stem cells (MSCs) have shown the ability to migrate to injury sites and exert therapeutic effects, though these benefits tend to be short-lived. The post-injury inflammatory microenvironment poses a significant barrier to the success of NSC therapies by impairing stem cell differentiation and survival. Therefore, immunosuppressive regimens are often employed to enhance NSC efficacy by creating a more supportive environment. Overall, while both NSCs and MSCs offer promising avenues for SCI treatment, long-term recovery likely requires multimodal approaches that address both neural regeneration and immune modulation. Continued research is essential to optimize these therapies and translate them into effective clinical treatments for patients with chronic SCI.
Antonios, J. P., Farah, G. J., Cleary, D. R., Martin, J. R., Ciacci, J. D. and Pham, M. H. (2019), “Immunosuppressive mechanisms for stem cell transplant survival in spinal cord injury”, Neurosurgical focus, Vol. 46 No. 3.
Baroudi, M., Rezk, A., Daher, M., Balmaceno-Criss, M., Gregoryczyk, J. G., Sharma, Y., McDonald, C. L., Diebo, B. G. and Daniels, A. H. (2024), “Management of traumatic spinal cord injury: A current concepts review of contemporary and future treatment”, Injury, Vol. 55 No. 6, pp. 111472.
Cheng, Z., Zhu, W., Cao, K., Wu, F., Li, J., Wang, G., Li, H., Lu, M., Ren, Y. and He, X. (2016), “Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury”, International Journal of Molecular Sciences, Vol. 17 No. 9, pp. 1380.
Chiu, A. K., Pease, T. J., Prakash, H., Oster, B. A., Smith, R. A., Sahlani, M., Ratanpal, A. S., Amin, I., Scalea, T. M., Bivona, L. J., Jauregui, J. J., Cavanaugh, D. L., Koh, E. Y. and Ludwig, S. C. (2024), “The changing epidemiology of traumatic spine injuries: a trends analysis of 26 years of patients at a major level 1 trauma center in the United States”, The Spine Journal, Vol. 24 No. 9, pp. 1561-70.
Denys, P., Chartier-Kastler, E., Even, A. and Joussain, C. (2021), “How to treat neurogenic bladder and sexual dysfunction after spinal cord lesion”, Revenue Neurologique, Vol. 177 No. 5, pp. 589-93.
Gelenitis, K., Santamaria, A., Pradarelli, J., Rieger, M., Inanici, F., Tefertiller, C., Field-Fote, E., Guest, J., Suggitt, J., Turner, A., D’Amico, J. M. and Moritz, C. (2025), “Non-invasive Transcutaneous Spinal Cord Stimulation Programming Recommendations for the Treatment of Upper Extremity Impairment in Tetraplegia”, Neuromodulation, Vol. 28 No. 1, pp. 162-73.
Guo, W., Zhang, X., Zhai, J. and Xue, J. (2022), “The roles and applications of neural stem cells in spinal cord injury repair”, Frontiers in Bioengineering and Biotechnology, Vol. 10.
Iversen, M. M., Harrison, A. T., Stanley, C. T. and Dalrymple, A. N. (2024), “Rehabilitation of motor and sensory function using spinal cord stimulation: Recent advances”, Current Opinion in Biomedical Engineering, Vol. 32, pp. 100566.
Kaur, H. (2025), “Stem Cell Therapy for Spinal Cord Injury: Investigating the Path to Neural Regeneration and Functional Restoration”, International Journal of Recent Innovations in Academic Research, Vol. 9 No. 2, pp. 23-30.
Lee, S., Nam, H., Joo, K. M. and Lee, S. H. (2022), “Advances in Neural Stem Cell Therapy for Spinal Cord Injury: Safety, Efficacy, and Future Perspectives”, Neurospine, Vol. 19 No. 4, pp. 946-60.
Levi, A. D., Anderson, K. D., Okonkwo, D. O., Park, P., Bryce, T. N., Kurpad, S. N., Aarabi, B., Hsieh, J. and Gant, K. (2019), “Clinical Outcomes from a Multi-Center Study of Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury”, Journal of Neurotrauma, Vol. 36, pp. 891-902.
Li, K., Chen, Z., Chang, X., Xue, R., Wang, H. and Guo, W. (2024), “Wnt signaling pathway in spinal cord injury: from mechanisms to potential applications”, Frontiers in molecular science, Vol. 17.
Liu, J., Qi, L., Bao, S., Yan, F., Chen, J., Yu, S. and Dong, C. (2024), “The acute spinal cord injury microenvironment and its impact on the homing of mesenchymal stem cells”, Experimental Neurology, Vol. 373, pp. 114682.
Li, W. Y., Qu, W. R., Li, Y., Wang, S. Y., Liu, D. M., Deng, L. X. and Wang, Y. (2024), “DBS in the restoration of motor functional recovery following spinal cord injury”, Frontiers in Neurology, Vol. 15.
Li, Y., Kumamaru, H., Vokes, T. J., Tran, A. N., Shevinsky, C. A., Graham, L., Archuleta, K., Limon, K. R., Lu, P., Blesch, A., Tuszynski, M. H. and Brock, J. H. (2024), “An improved method for generating human spinal cord neural stem cells”, Experimental Neurology, Vol. 376.
Mahler, J. L., Schneider, S., Wöllner, J., Pannek, J. and Krebs, J. (2025), “Impact of bladder management methods and other factors on sexual activity in women with chronic spinal cord injury/disease”, Sexual Medicine, Vol. 12 No. 6.
Martin, J. R., Cleary, D., Abraham, M. E., Mendoza, M., Cabrera, B., Jamieson, C., Marsala, M. and Ciacci, J. D. (2024), “Long-term clinical and safety outcomes from a single-site phase 1 study of neural stem cell transplantation for chronic thoracic spinal cord injury”, Cell Reports Medicine, Vol. 5 No. 12, pp. 101841.
Moreno-López, Y. and Hollis, E. R. (2021), “Sensory Circuit Remodeling and Movement Recovery After Spinal Cord Injury”, Frontiers in Neuroscience, Vol. 15.
Mu, Z., Qin, J., Zhou, X. and Wang, K. (2024), “Synergistic effects of human umbilical cord mesenchymal stem cells/neural stem cells and epidural electrical stimulation on spinal cord injury rehabilitation”, Scientific Reports, Vol. 14 No. 1, pp. 26090.
Sajjad, U., Ahmed, M., Iqbal, M. Z., Riaz, M., Mustafa, M., Biedermann, T., Klar, A. S. (2024), “Exploring mesenchymal stem cells homing mechanisms and improvement strategies”, Stem Cells Translational Medicine, Vol. 13, pp. 1161-77.
Shang, Z., Li, D., Chen, J., Wang, R., Wang, M., Zhang, B., Wang, X. and Wanyan, P. (2022), “What Is the Optimal Timing of Transplantation of Neural Stem Cells in Spinal Cord Injury? A Systematic Review and Network Meta-Analysis Based on Animal Studies”, Frontiers in Immunology, Vol. 13.
Srikandarajah, N., Alvi, M. A. and Fehlings, M. G. (2023), “Current insights into the management of spinal cord injury”, Journal of Orthopaedics, Vol. 41, pp. 8-13.
Tahmasebi, F. and Barati, S. (2022), “Effects of mesenchymal stem cell transplantation on spinal cord injury patients”, Cell and Tissue Research, Vol. 389, pp. 373-84.
Tiwari, S., Khan, S., Kumar, S. V., Rajak, R., Sultana, A., Pasha, S. A., Gauba, D., Ghosh, P., Khurana, T., Kulkarni, A., Reddy, Y. P., Khan, A. A. and Sharma, V. K. (2021), “Efficacy and safety of neural stem cell therapy for spinal cord injury: A systematic literature review”, Therapies, Vol. 76 No. 3, pp. 201-10.
Xia, Y., Zhu, J., Yang, R., Wang, H., Li, Y. and Fu, C. (2023), “Mesenchymal stem cells in the treatment of spinal cord injury: Mechanisms, current advances and
future challenges”, Frontiers in Immunology, Vol. 14.
Zeng, C. W. (2023), “Advancing Spinal Cord Injury Treatment through Stem Cell Therapy: A Comprehensive Review of Cell Types, Challenges, and Emerging Technologies in Regenerative Medicine”, International journal of molecular sciences, Vol. 24 No. 18, pp. 14349.
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