Efficacy of Growth Factor Gene-modified Stem Cells for Motor Function After Spinal Cord Injury in Rodents: a Systematic Review and Meta‑analysis

Overview

Journal Neurosurg Rev

Specialty Neurosurgery

Date 2024 Feb 18

PMID 38369598

Authors

Wen-Ya Shang

Ya-Feng Ren

Bing Li

Xiao-Meng Huang

Zhi-Lan Zhang

Jing Huang

Affiliations

Soon will be listed here.

Abstract

The efficacy of growth factor gene-modified stem cells in treating spinal cord injury (SCI) remains unclear. This study aims to evaluate the effectiveness of growth factor gene-modified stem cells in restoring motor function after SCI. Two reviewers searched four databases, including PubMed, Embase, Web of Science, and Scopus, to identify relevant records. Studies on rodents assessing the efficacy of transplanting growth factor gene-modified stem cells in restoring motor function after SCI were included. The results were reported using the standardized mean difference (SMD) with a 95% confidence interval (95% CI). Analyses showed that growth factor gene-modified stem cell transplantation improved motor function recovery in rodents with SCI compared to the untreated (SMD = 3.98, 95% CI 3.26-4.70, I = 86.8%, P < 0.0001) and stem cell (SMD = 2.53, 95% CI 1.93-3.13, I = 86.9%, P < 0.0001) groups. Using growth factor gene-modified neural stem/histone cells enhanced treatment efficacy. In addition, the effectiveness increased when viral vectors were employed for gene modification and high transplantation doses were administered during the subacute phase. Stem cells derived from the human umbilical cord exhibited an advantage in motor function recovery. However, the transplantation of growth factor gene-modified stem cells did not significantly improve motor function in male rodents (P = 0.136). Transplantation of growth factor gene-modified stem cells improved motor function in rodents after SCI, but claims of enhanced efficacy should be approached with caution. The safety of gene modification remains a significant concern, requiring additional efforts to enhance its clinical translatability.

References

Yuan S, Shi Z, Cao F, Li J, Feng S . Epidemiological Features of Spinal Cord Injury in China: A Systematic Review. Front Neurol. 2018; 9:683. PMC: 6113592. DOI: 10.3389/fneur.2018.00683. View

Jazayeri S, Rahimi-Movaghar V . Estimating TSCI incidence worldwide: a long road to drive. Spinal Cord. 2014; 52(6):502. DOI: 10.1038/sc.2014.51. View

Lu Y, Yang J, Wang X, Ma Z, Li S, Liu Z . Research progress in use of traditional Chinese medicine for treatment of spinal cord injury. Biomed Pharmacother. 2020; 127:110136. DOI: 10.1016/j.biopha.2020.110136. View

Li F, Wang H, Chen H, Guo J, Dang X, Ru Y . Mechanism of Ferroptosis and Its Role in Spinal Cord Injury. Front Neurol. 2022; 13:926780. PMC: 9218271. DOI: 10.3389/fneur.2022.926780. View

Lin S, Mei X . Role of NLRP3 Inflammasomes in Neuroinflammation Diseases. Eur Neurol. 2020; 83(6):576-580. DOI: 10.1159/000509798. View

Zhou H, Jing S, Xiong W, Zhu Y, Duan X, Li R . Metal-organic framework materials promote neural differentiation of dental pulp stem cells in spinal cord injury. J Nanobiotechnology. 2023; 21(1):316. PMC: 10478386. DOI: 10.1186/s12951-023-02001-2. View

Anderson M, Squair J, Gautier M, Hutson T, Kathe C, Barraud Q . Natural and targeted circuit reorganization after spinal cord injury. Nat Neurosci. 2022; 25(12):1584-1596. DOI: 10.1038/s41593-022-01196-1. View

Cao Y, DiPiro N, Jarnecke M, Krause J . Social participation as a mediator of the relationships of socioeconomic factors and longevity after traumatic spinal cord injury. Spinal Cord. 2022; 60(9):799-804. PMC: 9444867. DOI: 10.1038/s41393-022-00794-x. View

Zheng Y, Mao Y, Yuan T, Xu D, Cheng L . Multimodal treatment for spinal cord injury: a sword of neuroregeneration upon neuromodulation. Neural Regen Res. 2020; 15(8):1437-1450. PMC: 7059565. DOI: 10.4103/1673-5374.274332. View

10.

Kiyotake E, Martin M, Detamore M . Regenerative rehabilitation with conductive biomaterials for spinal cord injury. Acta Biomater. 2020; 139:43-64. DOI: 10.1016/j.actbio.2020.12.021. View

11.

Zipser C, Cragg J, Guest J, Fehlings M, Jutzeler C, Anderson A . Cell-based and stem-cell-based treatments for spinal cord injury: evidence from clinical trials. Lancet Neurol. 2022; 21(7):659-670. DOI: 10.1016/S1474-4422(21)00464-6. View

12.

Mohammed R, Opara K, Lall R, Ojha U, Xiang J . Evaluating the effectiveness of anti-Nogo treatment in spinal cord injuries. Neural Dev. 2020; 15(1):1. PMC: 6953157. DOI: 10.1186/s13064-020-0138-9. View

13.

Roy A, Pathak Z, Kumar H . Strategies to neutralize RhoA/ROCK pathway after spinal cord injury. Exp Neurol. 2021; 343:113794. DOI: 10.1016/j.expneurol.2021.113794. View

14.

Li J . Weak direct current (DC) electric fields as a therapy for spinal cord injuries: review and advancement of the oscillating field stimulator (OFS). Neurosurg Rev. 2019; 42(4):825-834. DOI: 10.1007/s10143-018-01068-y. View

15.

Ouaamari Y, Van den Bos J, Willekens B, Cools N, Wens I . Neurotrophic Factors as Regenerative Therapy for Neurodegenerative Diseases: Current Status, Challenges and Future Perspectives. Int J Mol Sci. 2023; 24(4). PMC: 9968045. DOI: 10.3390/ijms24043866. View

16.

Chang D, Cho H, Hwang S, Lee N, Choi C, Lee H . Therapeutic Effect of BDNF-Overexpressing Human Neural Stem Cells (F3.BDNF) in a Contusion Model of Spinal Cord Injury in Rats. Int J Mol Sci. 2021; 22(13). PMC: 8269438. DOI: 10.3390/ijms22136970. View

17.

Yousefifard M, Askarian-Amiri S, Nasseri Maleki S, Alavi S, Madani Neishaboori A, Haghani L . Combined application of neural stem/progenitor cells and scaffolds on locomotion recovery following spinal cord injury in rodents: a systematic review and meta-analysis. Neurosurg Rev. 2022; 45(6):3469-3488. DOI: 10.1007/s10143-022-01859-4. View

18.

Feng Y, Li Y, Shen P, Wang B . Gene-Modified Stem Cells for Spinal Cord Injury: a Promising Better Alternative Therapy. Stem Cell Rev Rep. 2022; 18(8):2662-2682. DOI: 10.1007/s12015-022-10387-z. View

19.

Nie W, Zhang D, Wang L . Growth Factor Gene-Modified Mesenchymal Stem Cells in Tissue Regeneration. Drug Des Devel Ther. 2020; 14:1241-1256. PMC: 7105364. DOI: 10.2147/DDDT.S243944. View

20.

Pan B, Wu X, Zeng X, Chen J, Zhang W, Cheng X . Transplantation of Wnt4-modified neural stem cells mediate M2 polarization to improve inflammatory micro-environment of spinal cord injury. Cell Prolif. 2023; 56(8):e13415. PMC: 10392051. DOI: 10.1111/cpr.13415. View