Advances in stem cell transplantation for traumatic spinal cord injury at different stages_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

JIN Yuanzhi , RONG Xin ,  LIU Hao

Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China;

Corresponding author：

LIU Hao, Email: liuhao6304@163.com

Keywords：

Spine cord injury; stem cell transplantation; clinical trial

DOI：

10.7507/1002-1892.202302028

Video：

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Objective To summarize the research progress of stem cell transplantation in treating spinal cord injury (SCI) at different stages based on the pathophysiological mechanism of SCI. Methods The relevant research literature at home and abroad was extensively reviewed to explore the impact of transplantation timing on the effectiveness of stem cell transplantation in treating SCI. Results Researchers performed different types of stem cell transplantation for subjects at different stages of SCI through different transplantation approaches. Clinical trials have proved the safety and feasibility of stem cell transplantation at acute, subacute, and chronic stages, which can alleviate inflammation at the injured site and restore the function of the damaged nerve cells. But the reliable clinical trials comparing the effectiveness of stem cell transplantation at different stages of SCI are still lacking. Conclusion Stem cell transplantation has a good prospect in treating SCI. In the future, the multi-center, large sample randomized controlled clinical trials are needed, with a focus on the long-term effectiveness of stem cell transplantation.

Citation： JIN Yuanzhi, RONG Xin, LIU Hao. Advances in stem cell transplantation for traumatic spinal cord injury at different stages. Chinese Journal of Reparative and Reconstructive Surgery, 2023, 37(6): 721-726. doi: 10.7507/1002-1892.202302028 Copy

1.	Ahuja CS, Nori S, Tetreault L, et al. Traumatic spinal cord injury-repair and regeneration. Neurosurgery, 2017, 80(3S): S9-S22. doi: 10.1093/neuros/nyw080.
2.	Gao L, Peng Y, Xu W, et al. Progress in stem cell therapy for spinal cord injury. Stem Cells Int, 2020, 2020: 2853650. doi: 10.1155/2020/2853650.
3.	Blommestein HM, Verelst SG, Huijgens PC, et al. Real-world costs of autologous and allogeneic stem cell transplantations for haematological diseases: a multicentre study. Ann Hematol, 2012, 91(12): 1945-1952.
4.	Assinck P, Duncan GJ, Hilton BJ, et al. Cell transplantation therapy for spinal cord injury. Nat Neurosci, 2017, 20(5): 637-647.
5.	Anjum A, Yazid MD, Fauzi Daud M, et al. Spinal cord injury: pathophysiology, multimolecular interactions, and underlying recovery mechanisms. Int J Mol Sci, 2020, 21(20): 7533. doi: 10.3390/ijms21207533.
6.	Oyinbo CA. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Wars), 2011, 71(2): 281-299.
7.	Alizadeh A, Dyck SM, Karimi-Abdolrezaee S. Traumatic spinal cord injury: an overview of pathophysiology, models and acute injury mechanisms. Front Neurol, 2019, 10: 282. doi: 10.3389/fneur.2019.00282.
8.	Fan B, Wei Z, Yao X, et al. Microenvironment imbalance of spinal cord injury. Cell Transplant, 2018, 27(6): 853-866.
9.	Zhao H, Sun QL, Duan LJ, et al. Is cell transplantation a reliable therapeutic strategy for spinal cord injury in clinical practice? A systematic review and meta-analysis from 22 clinical controlled trials. Eur Spine J, 2019, 28(5): 1092-1112.
10.	Zholudeva LV, Lane MA. Transplanting cells for spinal cord repair: who, what, when, where and why? Cell Transplant, 2019, 28(4): 388-399.
11.	Zipser CM, Cragg JJ, Guest JD, et al. Cell-based and stem-cell-based treatments for spinal cord injury: evidence from clinical trials. Lancet Neurol, 2022, 21(7): 659-670.
12.	Park HC, Shim YS, Ha Y, et al. Treatment of complete spinal cord injury patients by autologous bone marrow cell transplantation and administration of granulocyte-macrophage colony stimulating factor. Tissue Eng, 2005, 11(5-6): 913-922.
13.	Yoon SH, Shim YS, Park YH, et al. Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: Phase Ⅰ/Ⅱ clinical trial. Stem Cells, 2007, 25(8): 2066-2073.
14.	Chhabra HS, Sarda K, Arora M, et al. Autologous bone marrow cell transplantation in acute spinal cord injury-an Indian pilot study. Spinal Cord, 2016, 54(1): 57-64.
15.	Karamouzian S, Nematollahi-Mahani SN, Nakhaee N, et al. Clinical safety and primary efficacy of bone marrow mesenchymal cell transplantation in subacute spinal cord injured patients. Clin Neurol Neurosurg, 2012, 114(7): 935-939.
16.	Shin JC, Kim KN, Yoo J, et al. Clinical trial of human fetal brain-derived neural stem/progenitor cell transplantation in patients with traumatic cervical spinal cord injury. Neural Plast, 2015, 2015: 630932. doi: 10.1155/2015/630932.
17.	Geffner LF, Santacruz P, Izurieta M, et al. Administration of autologous bone marrow stem cells into spinal cord injury patients via multiple routes is safe and improves their quality of life: comprehensive case studies. Cell Transplant, 2008, 17(12): 1277-1293.
18.	Syková E, Homola A, Mazanec R, et al. Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury. Cell Transplant, 2006, 15(8-9): 675-687.
19.	Moviglia GA, Fernandez Viña R, Brizuela JA, et al. Combined protocol of cell therapy for chronic spinal cord injury. Report on the electrical and functional recovery of two patients. Cytotherapy, 2006, 8(3): 202-209.
20.	El-Kheir WA, Gabr H, Awad MR, et al. Autologous bone marrow-derived cell therapy combined with physical therapy induces functional improvement in chronic spinal cord injury patients. Cell Transplant, 2014, 23(6): 729-745.
21.	Levi AD, Anderson KD, Okonkwo DO, et al. Clinical outcomes from a multi-center study of human neural stem cell transplantation in chronic cervical spinal cord injury. J Neurotrauma, 2019, 36(6): 891-902.
22.	Chernykh ER, Stupak VV, Muradov GM, et al. Application of autologous bone marrow stem cells in the therapy of spinal cord injury patients. Bull Exp Biol Med, 2007, 143(4): 543-547.
23.	Cheng H, Liu X, Hua R, et al. Clinical observation of umbilical cord mesenchymal stem cell transplantation in treatment for sequelae of thoracolumbar spinal cord injury. J Transl Med, 2014, 12: 253. doi: 10.1186/s12967-014-0253-7.
24.	Oh SK, Choi KH, Yoo JY, et al. A phase Ⅲ clinical trial showing limited efficacy of autologous mesenchymal stem cell therapy for spinal cord injury. Neurosurgery, 2016, 78(3): 436-447.
25.	Kishk NA, Gabr H, Hamdy S, et al. Case control series of intrathecal autologous bone marrow mesenchymal stem cell therapy for chronic spinal cord injury. Neurorehabil Neural Repair, 2010, 24(8): 702-708.
26.	Dai G, Liu X, Zhang Z, et al. Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury. Brain Res, 2013, 1533: 73-79.
27.	Chen L, Huang H, Xi H, et al. A prospective randomized double-blind clinical trial using a combination of olfactory ensheathing cells and Schwann cells for the treatment of chronic complete spinal cord injuries. Cell Transplant, 2014, 23 Suppl 1: S35-S44.
28.	Honmou O, Yamashita T, Morita T, et al. Intravenous infusion of auto serum-expanded autologous mesenchymal stem cells in spinal cord injury patients: 13 case series. Clin Neurol Neurosurg, 2021, 203: 106565. doi: 10.1016/j.clineuro.2021.106565.
29.	Fessler RG, Ehsanian R, Liu CY, et al. A phase 1/2a dose-escalation study of oligodendrocyte progenitor cells in individuals with subacute cervical spinal cord injury. J Neurosurg Spine, 2022, 37(6): 812-820.
30.	Gant KL, Guest JD, Palermo AE, et al. Phase 1 safety trial of autologous human Schwann cell transplantation in chronic spinal cord injury. J Neurotrauma, 2022, 39(3-4): 285-299.

1. Ahuja CS, Nori S, Tetreault L, et al. Traumatic spinal cord injury-repair and regeneration. Neurosurgery, 2017, 80(3S): S9-S22. doi: 10.1093/neuros/nyw080.
2. Gao L, Peng Y, Xu W, et al. Progress in stem cell therapy for spinal cord injury. Stem Cells Int, 2020, 2020: 2853650. doi: 10.1155/2020/2853650.
3. Blommestein HM, Verelst SG, Huijgens PC, et al. Real-world costs of autologous and allogeneic stem cell transplantations for haematological diseases: a multicentre study. Ann Hematol, 2012, 91(12): 1945-1952.
4. Assinck P, Duncan GJ, Hilton BJ, et al. Cell transplantation therapy for spinal cord injury. Nat Neurosci, 2017, 20(5): 637-647.
5. Anjum A, Yazid MD, Fauzi Daud M, et al. Spinal cord injury: pathophysiology, multimolecular interactions, and underlying recovery mechanisms. Int J Mol Sci, 2020, 21(20): 7533. doi: 10.3390/ijms21207533.
6. Oyinbo CA. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Wars), 2011, 71(2): 281-299.
7. Alizadeh A, Dyck SM, Karimi-Abdolrezaee S. Traumatic spinal cord injury: an overview of pathophysiology, models and acute injury mechanisms. Front Neurol, 2019, 10: 282. doi: 10.3389/fneur.2019.00282.
8. Fan B, Wei Z, Yao X, et al. Microenvironment imbalance of spinal cord injury. Cell Transplant, 2018, 27(6): 853-866.
9. Zhao H, Sun QL, Duan LJ, et al. Is cell transplantation a reliable therapeutic strategy for spinal cord injury in clinical practice? A systematic review and meta-analysis from 22 clinical controlled trials. Eur Spine J, 2019, 28(5): 1092-1112.
10. Zholudeva LV, Lane MA. Transplanting cells for spinal cord repair: who, what, when, where and why? Cell Transplant, 2019, 28(4): 388-399.
11. Zipser CM, Cragg JJ, Guest JD, et al. Cell-based and stem-cell-based treatments for spinal cord injury: evidence from clinical trials. Lancet Neurol, 2022, 21(7): 659-670.
12. Park HC, Shim YS, Ha Y, et al. Treatment of complete spinal cord injury patients by autologous bone marrow cell transplantation and administration of granulocyte-macrophage colony stimulating factor. Tissue Eng, 2005, 11(5-6): 913-922.
13. Yoon SH, Shim YS, Park YH, et al. Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: Phase Ⅰ/Ⅱ clinical trial. Stem Cells, 2007, 25(8): 2066-2073.
14. Chhabra HS, Sarda K, Arora M, et al. Autologous bone marrow cell transplantation in acute spinal cord injury-an Indian pilot study. Spinal Cord, 2016, 54(1): 57-64.
15. Karamouzian S, Nematollahi-Mahani SN, Nakhaee N, et al. Clinical safety and primary efficacy of bone marrow mesenchymal cell transplantation in subacute spinal cord injured patients. Clin Neurol Neurosurg, 2012, 114(7): 935-939.
16. Shin JC, Kim KN, Yoo J, et al. Clinical trial of human fetal brain-derived neural stem/progenitor cell transplantation in patients with traumatic cervical spinal cord injury. Neural Plast, 2015, 2015: 630932. doi: 10.1155/2015/630932.
17. Geffner LF, Santacruz P, Izurieta M, et al. Administration of autologous bone marrow stem cells into spinal cord injury patients via multiple routes is safe and improves their quality of life: comprehensive case studies. Cell Transplant, 2008, 17(12): 1277-1293.
18. Syková E, Homola A, Mazanec R, et al. Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury. Cell Transplant, 2006, 15(8-9): 675-687.
19. Moviglia GA, Fernandez Viña R, Brizuela JA, et al. Combined protocol of cell therapy for chronic spinal cord injury. Report on the electrical and functional recovery of two patients. Cytotherapy, 2006, 8(3): 202-209.
20. El-Kheir WA, Gabr H, Awad MR, et al. Autologous bone marrow-derived cell therapy combined with physical therapy induces functional improvement in chronic spinal cord injury patients. Cell Transplant, 2014, 23(6): 729-745.
21. Levi AD, Anderson KD, Okonkwo DO, et al. Clinical outcomes from a multi-center study of human neural stem cell transplantation in chronic cervical spinal cord injury. J Neurotrauma, 2019, 36(6): 891-902.
22. Chernykh ER, Stupak VV, Muradov GM, et al. Application of autologous bone marrow stem cells in the therapy of spinal cord injury patients. Bull Exp Biol Med, 2007, 143(4): 543-547.
23. Cheng H, Liu X, Hua R, et al. Clinical observation of umbilical cord mesenchymal stem cell transplantation in treatment for sequelae of thoracolumbar spinal cord injury. J Transl Med, 2014, 12: 253. doi: 10.1186/s12967-014-0253-7.
24. Oh SK, Choi KH, Yoo JY, et al. A phase Ⅲ clinical trial showing limited efficacy of autologous mesenchymal stem cell therapy for spinal cord injury. Neurosurgery, 2016, 78(3): 436-447.
25. Kishk NA, Gabr H, Hamdy S, et al. Case control series of intrathecal autologous bone marrow mesenchymal stem cell therapy for chronic spinal cord injury. Neurorehabil Neural Repair, 2010, 24(8): 702-708.
26. Dai G, Liu X, Zhang Z, et al. Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury. Brain Res, 2013, 1533: 73-79.
27. Chen L, Huang H, Xi H, et al. A prospective randomized double-blind clinical trial using a combination of olfactory ensheathing cells and Schwann cells for the treatment of chronic complete spinal cord injuries. Cell Transplant, 2014, 23 Suppl 1: S35-S44.
28. Honmou O, Yamashita T, Morita T, et al. Intravenous infusion of auto serum-expanded autologous mesenchymal stem cells in spinal cord injury patients: 13 case series. Clin Neurol Neurosurg, 2021, 203: 106565. doi: 10.1016/j.clineuro.2021.106565.
29. Fessler RG, Ehsanian R, Liu CY, et al. A phase 1/2a dose-escalation study of oligodendrocyte progenitor cells in individuals with subacute cervical spinal cord injury. J Neurosurg Spine, 2022, 37(6): 812-820.
30. Gant KL, Guest JD, Palermo AE, et al. Phase 1 safety trial of autologous human Schwann cell transplantation in chronic spinal cord injury. J Neurotrauma, 2022, 39(3-4): 285-299.

Chinese Journal of Reparative and Reconstructive Surgery

Advances in stem cell transplantation for traumatic spinal cord injury at different stages

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