Stem cells application for the treatment of traumatic brain injury

Authors

DOI:

https://doi.org/10.25305/unj.189596

Keywords:

traumatic brain injury, stem cells, transplantation, clinical trials

Abstract

Traumatic brain injury (TBI) is a global medical and socio-economic problem. Traumatic injuries of the skull and brain make up 30-40 % of all traumas and are the first in terms of mortality and disability among people of working age. High expectations for the treatment of TBI and its consequences are due to the use of stem cell (SCs) therapy. The present review examines the pathogenetic prerequisites for SCs application in TBI effects treatment: generalizes information about the primary and secondary changes in nerve tissue after TBI (cellular, tissue, organ, systemic level) and functional neurological disorders (physical, motor, cognitive, behavioral symptoms); emphasizes the impossibility of restoring neurological functions without restoring brain structures and functions. The paper proposes the main directions of application of SCs for the TBI effects treatment - stimulation of endogenous SCs, transplantation of exogenous SCs and a combination of these approaches. The sources and types of SCs considered for the restoration of the damaged organ and its functional parameters are characterized in detail: embryonic (ESCs), neurogenic (NSC/NPCs), stromal (SCs of bone marrow, adipose tissue, including mesenchymal (MSCs), hematopoietic (HSCs), umbilical cord blood SCs, induced pluripotent SCs (iPSCs). The results of preclinical studies of the different SCs types used in animals with TBI experimental models are summarized. The actual information regarding clinical trials on the safety and efficacy of the SCs application in the TBI effects treatment in the directions of endogenous SCs stimulation (drug administration, physical methods) and exogenous SCs transplantation (autologous SCs (bone marrow, adipose tissue) and allogeneic SCs (MSCs, bone marrow SCs, umbilical cord blood SCs) is analyzed. The gradual accumulation of clinical trial results will allow future meta-analytic studies and the development of certified standardized protocols for the treatment of TBI consequences using the benefits of SCs.

Author Biographies

Larysa D. Liubich, Rodomanov Neurosurgery Institute, Kyiv

Tissue Culture Laboratory

Diana M. Egorova, Rodomanov Neurosurgery Institute, Kyiv

Tissue Culture Laboratory

References

1. Chayka AV, Zaben’ko YY, Labunets IF, Pivneva TA. [Traumatic brain injury: pathogenesis, experimental models, prospects of cell-based therapy]. Cell and Organ Transplantology. 2017;5(2):209-215. Russian. [CrossRef]

2. Pedachenko EG, Shlapak IP, Guk AP, Pilipenko MN. [Cherepno-mozgovaya travma: sovremennye printsipy neotlozhnoy pomoshchi]. Kiev: ZAO «Vіpol»; 2009. Russian.

3. Pedachenko EG. [Neurosurgery in Ukraine: nowadays and perspectives]. Ukrainian Neurosurgical Journal. 2018;(1):5-18. Ukrainian. [CrossRef]

4. Puras JV, Talypov AE. [Risk factors for unfavorable outcome in surgical treatment of acute head injury]. Russian Journal of Neurosurgery. 2013;(2):8-16. Russian. [CrossRef]

5. Peeters W, van den Brande R, Polinder S, Brazinova A, Steyerberg EW, Lingsma HF, Maas AI. Epidemiology of traumatic brain injury in Europe. Acta Neurochir (Wien). 2015 Oct;157(10):1683-96. [CrossRef] [PubMed] [PubMed Central]

6. Biloshytsky VV, Kobyletsky OYa. [Possibilities of biochemical biomarkers in prognosis of traumatic brain injury course]. Ukrainian Neurosurgical Journal. 2015;(1):4-15. Ukrainian. [CrossRef]

7. Pedachenko EG, Biloshytsky VV, Mikhal’sky SA, Gridina NY, Kvitnitskaya-Ryzhova TY. [The effect of gene therapy with the APOE3 Gene on structural and functional manifestations of secondary hippocampal damages in experimental traumatic brain injury]. Zh Vopr Neirokhir Im N N Burdenko. 2015;79(2):21-32. English, Russian. [CrossRef] [PubMed]

8. Shurpyak IV. [Mild traumatic brain injury and its aftermath]. Semejnaâ Medicina. 2013;(1):67-73. Ukrainian. http://nbuv.gov.ua/UJRN/simmed_2013_1_16

9. Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci. 2007 Jan;8(1):57-69. [CrossRef] [PubMed]

10. Ransohoff RM, Perry VH. Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol. 2009;27:119-45. [CrossRef] [PubMed]

11. Blaylock RL, Maroon J. Immunoexcitotoxicity as a central mechanism in chronic traumatic encephalopathy - A unifying hypothesis. Surg Neurol Int. 2011;2:107. [CrossRef] [PubMed] [PubMed Central]

12. Homsi S, Piaggio T, Croci N, Noble F, Plotkine M, Marchand-Leroux C, Jafarian-Tehrani M. Blockade of acute microglial activation by minocycline promotes neuroprotection and reduces locomotor hyperactivity after closed head injury in mice: a twelve-week follow-up study. J Neurotrauma. 2010 May;27(5):911-21. [CrossRef] [PubMed]

13. Polovnikov EV, Tsvetovsky SB, Stupak VV, Vasiliev IA, Shevela EYa, Ostanin AA, Chernykh ER. [Influence of mesenchymal stromal cells on the dynamics of restoration of the brain electrophysiological activity in a model of traumatic brain injury in rats]. Fundamental research. 2014;(10-1):136-40. Russian. http://www.fundamental-research.ru/ru/article/view?id=35229

14. Walsh JG, Muruve DA, Power C. Inflammasomes in the CNS. Nat Rev Neurosci. 2014 Feb;15(2):84-97. [CrossRef] [PubMed]

15. Corps KN, Roth TL, McGavern DB. Inflammation and neuroprotection in traumatic brain injury. JAMA Neurol. 2015;72(3):355-62. [CrossRef] [PubMed] [PubMed Central]

16. Gadani SP, Walsh JT, Lukens JR, Kipnis J. Dealing with Danger in the CNS: The Response of the Immune System to Injury. Neuron. 2015 Jul;87(1):47-62. [CrossRef] [PubMed] [PubMed Central]

17. Shkolnyk VM, Fesenko GD, Golyk VA, Pogorelova SA, Pashkovskyi VI, Huk AP. [Remote cognitive impairments after traumatic brain injury as a disability cause]. Ukrainian Neurosurgical Journal. 2015;2:5-10. Ukrainia. [CrossRef]

18. Potapov AA, Krylov VV, Likhterman LB, Talypov AE, Gavrilov AG, Petrikov SS. [Treatment of victims of severe traumatic brain injury: clinical recommendations]. Moscow: Association of Neurosurgeons of Russia; 2014. Russian.

19. Dekmak A, Mantash S, Shaito A, Toutonji A, Ramadan N, Ghazale H, Kassem N, Darwish H, Zibara K. Stem cells and combination therapy for the treatment of traumatic brain injury. Behav Brain Res. 2018 Mar 15;340:49-62. [CrossRef] [PubMed]

20. Ludwig PE, Thankam FG, Patil AA, Chamczuk AJ, Agrawal DK. Brain injury and neural stem cells. Neural Regen Res. 2018 Jan;13(1):7-18. [CrossRef] [PubMed] [PubMed Central]

21. Weston NM, Sun D. The Potential of Stem Cells in Treatment of Traumatic Brain Injury. Curr Neurol Neurosci Rep. 2018 Jan 25;18(1):1. [CrossRef] [PubMed] [PubMed Central]

22. Riess P, Molcanyi M, Bentz K, Maegele M, Simanski C, Carlitscheck C, Schneider A, Hescheler J, Bouillon B, Schäfer U, Neugebauer E. Embryonic stem cell transplantation after experimental traumatic brain injury dramatically improves neurological outcome, but may cause tumors. J Neurotrauma. 2007 Jan;24(1):216-25. Erratum in: J Neurotrauma. 2007;24(2):433. [CrossRef] [PubMed]

23. Parent JM. The role of seizure-induced neurogenesis in epileptogenesis and brain repair. Epilepsy Res. 2002 Jun;50(1-2):179-89. [CrossRef] [PubMed]

24. van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH. Functional neurogenesis in the adult hippocampus. Nature. 2002 Feb 28;415(6875):1030-4. [CrossRef] [PubMed]

25. Gomazkov OA. [Neyrogenez kak adaptivnaya funktsiya mozga]. Moscow: Ikar; 2013. Russian.

26. Rolfe A, Sun D. Stem Cell Therapy in Brain Trauma: Implications for Repair and Regeneration of Injured Brain in Experimental TBI Models. In: Kobeissy FH, editor. Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects. Boca Raton (FL): CRC Press/Taylor & Francis; 2015. Chapter 42. https://www.ncbi.nlm.nih.gov/books/NBK299210/

27. Haus DL, López-Velázquez L, Gold EM, Cunningham KM, Perez H, Anderson AJ, Cummings BJ. Transplantation of human neural stem cells restores cognition in an immunodeficient rodent model of traumatic brain injury. Exp Neurol. 2016 Jul;281:1-16. [CrossRef] [PubMed]

28. Beretta S, Cunningham KM, Haus DL, Gold EM, Perez H, López-Velázquez L, Cummings BJ. Effects of Human ES-Derived Neural Stem Cell Transplantation and Kindling in a Rat Model of Traumatic Brain Injury. Cell Transplant. 2017 Jul;26(7):1247-1261. [CrossRef] [PubMed] [PubMed Central]

29. Toft A, Scott DT, Barnett SC, Riddell JS. Electrophysiological evidence that olfactory cell transplants improve function after spinal cord injury. Brain. 2007 Apr;130(Pt 4):970-84. [CrossRef] [PubMed]

30. Richter M, Westendorf K, Roskams AJ. Culturing olfactory ensheathing cells from the mouse olfactory epithelium. Methods Mol Biol. 2008;438:95-102. [CrossRef] [PubMed]

31. Wang YC, Xia QJ, Ba YC, Wang TY, LiN N, Zou Y, Shang FF, Zhou XF, Wang TH, Fu XM, Qi JG. Transplantation of olfactory ensheathing cells promotes the recovery of neurological functions in rats with traumatic brain injury associated with downregulation of Bad. Cytotherapy. 2014 Jul;16(7):1000-10. [CrossRef] [PubMed]

32. Liu SJ, Zou Y, Belegu V, Lv LY, Lin N, Wang TY, McDonald JW, Zhou X, Xia QJ, Wang TH. Co-grafting of neural stem cells with olfactory ensheathing cells promotes neuronal restoration in traumatic brain injury with an anti-inflammatory mechanism. J Neuroinflammation. 2014 Apr 2;11:66. [CrossRef] [PubMed] [PubMed Central]

33. Balyabin AV, Mukhina IV. [Transplantation of autologous neural stem cells of the olfactory epithelium in the treatment effects severe traumatic brain injury (review)]. Mezhdunarodnyy zhurnal prikladnykh i fundamental’nykh issledovaniy. 2015;(12-9):1606-1612. Russian. https://applied-research.ru/ru/article/view?id=8202

34. Mahmood A, Lu D, Qu C, Goussev A, Chopp M. Long-term recovery after bone marrow stromal cell treatment of traumatic brain injury in rats. J Neurosurg. 2006 Feb;104(2):272-7. [CrossRef] [PubMed]

35. Lu D, Mahmood A, Qu C, Hong X, Kaplan D, Chopp M. Collagen scaffolds populated with human marrow stromal cells reduce lesion volume and improve functional outcome after traumatic brain injury. Neurosurgery. 2007 Sep;61(3):596-602; discussion 602-3. [CrossRef] [PubMed] [PubMed Central]

36. Xiong Y, Qu C, Mahmood A, Liu Z, Ning R, Li Y, Kaplan DL, Schallert T, Chopp M. Delayed transplantation of human marrow stromal cell-seeded scaffolds increases transcallosal neural fiber length, angiogenesis, and hippocampal neuronal survival and improves functional outcome after traumatic brain injury in rats. Brain Res. 2009 Mar 31;1263:183-91. [CrossRef] [PubMed] [PubMed Central]

37. Bonilla C, Zurita M, Otero L, Aguayo C, Vaquero J. Delayed intralesional transplantation of bone marrow stromal cells increases endogenous neurogenesis and promotes functional recovery after severe traumatic brain injury. Brain Inj. 2009 Aug;23(9):760-9. [CrossRef] [PubMed]

38. Li Y, Chopp M. Marrow stromal cell transplantation in stroke and traumatic brain injury. Neurosci Lett. 2009 Jun 12;456(3):120-3. [CrossRef] [PubMed] [PubMed Central]

39. Grigorian AS, Gilerovich EG, Pavlichenko NN, Kruglyakov PV, Sokolova IB, Polyntsev DG. [The effects of multipatent mesenchymal stem cells transplantation on post-traumatic processes after the experimental traumatic brain injury]. Cell Transplantology and Tissue Engineering. 2009; 4(3):58-67. Russian. https://elibrary.ru/item.asp?id=12856273

40. Gao J, Grill RJ, Dunn TJ, Bedi S, Labastida JA, Hetz RA, Xue H, Thonhoff JR,DeWitt DS, Prough DS, Cox CS Jr, Wu P. Human Neural Stem Cell Transplantation-Mediated Alteration of Microglial/Macrophage Phenotypes after Traumatic Brain Injury. Cell Transplant. 2016 Oct;25(10):1863-1877. [CrossRef] [PubMed]

41. Hong SQ, Zhang HT, You J, Zhang MY, Cai YQ, Jiang XD, Xu RX. Comparison of transdifferentiated and untransdifferentiated human umbilical mesenchymal stem cells in rats after traumatic brain injury. Neurochem Res. 2011 Dec;36(12):2391-400. [CrossRef] [PubMed]

42. Lam PK, Lo AW, Wang KK, Lau HC, Leung KK, Li KT, Lai PB, Poon WS. Transplantation of mesenchymal stem cells to the brain by topical application in an experimental traumatic brain injury model. J Clin Neurosci. 2013 Feb;20(2):306-9. [CrossRef] [PubMed]

43. Gennai S, Monsel A, Hao Q, Liu J, Gudapati V, Barbier EL, Lee JW. Cell-based therapy for traumatic brain injury. Br J Anaesth. 2015 Aug;115(2):203-12. [CrossRef] [PubMed] [PubMed Central]

44. Galindo LT, Filippo TR, Semedo P, Ariza CB, Moreira CM, Camara NO, Porcionatto MA. Mesenchymal stem cell therapy modulates the inflammatory response in experimental traumatic brain injury. Neurol Res Int. 2011;2011:564089. [CrossRef] [PubMed] [PubMed Central]

45. Sun D, Gugliotta M, Rolfe A, Reid W, McQuiston AR, Hu W, Young H. Sustained survival and maturation of adult neural stem/progenitor cells after transplantation into the injured brain. J Neurotrauma. 2011 Jun;28(6):961-72. [CrossRef] [PubMed] [PubMed Central]

46. Thomaidou D. Neural stem cell transplantation in an animal model of traumatic brain injury. Methods Mol Biol. 2014;1210:9-21. [CrossRef] [PubMed]

47. Bonilla C, Zurita M, Aguayo C, Rodríguez A, Vaquero J. Is the subarachnoid administration of mesenchymal stromal cells a useful strategy to treat chronic brain damage? Cytotherapy. 2014 Nov;16(11):1501-1510. [CrossRef] [PubMed]

48. Gao J, Prough DS, McAdoo DJ, Grady JJ, Parsley MO, Ma L, Tarensenko YI, Wu P. Transplantation of primed human fetal neural stem cells improves cognitive function in rats after traumatic brain injury. Exp Neurol. 2006 Oct;201(2):281-92. [CrossRef] [PubMed]

49. Tate CC, Case CC. Mesenchymal stromal cells to treat brain injury. Advanced topics in neurological disorders. In Ken-Shiung Chen, editor. Neurological disorders. InTech; 2012. p.45-78. http://cdn.intechopen.com/pdfs/32478/InTech-Mesenchymal_stromal_cells_to_treat_brain_injury.pdf

50. Walker PA, Bedi SS, Shah SK, Jimenez F, Xue H, Hamilton JA, Smith P, Thomas CP, Mays RW, Pati S, Cox CS Jr. Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population. J Neuroinflammation. 2012 Sep 28;9:228. [CrossRef] [PubMed] [PubMed Central]

51. Wang S, Cheng H, Dai G, Wang X, Hua R, Liu X, Wang P, Chen G, Yue W, An Y. Umbilical cord mesenchymal stem cell transplantation significantly improves neurological function in patients with sequelae of traumatic brain injury. Brain Res. 2013 Sep 26;1532:76-84. [CrossRef] [PubMed]

52. Li J, Zhu H, Liu Y, Li Q, Lu S, Feng M, Xu Y, Huang L, Ma C, An Y, Zhao RC, Wang R, Qin C. Human mesenchymal stem cell transplantation protects against cerebral ischemic injury and upregulates interleukin-10 expression in Macaca fascicularis. Brain Res. 2010 Jun 2;1334:65-72. [CrossRef] [PubMed]

53. Xin H, Li Y, Shen LH, Liu X, Wang X, Zhang J, Pourabdollah-Nejad D S, Zhang C, Zhang L, Jiang H, Zhang ZG, Chopp M. Increasing tPA activity in astrocytes induced by multipotent mesenchymal stromal cells facilitate neurite outgrowth after stroke in the mouse. PLoS One. 2010 Feb 3;5(2):e9027. [CrossRef] [PubMed] [PubMed Central]

54. Sun T, Ma QH. Repairing neural injuries using human umbilical cord blood. Mol Neurobiol. 2013 Jun;47(3):938-45. [CrossRef] [PubMed] [PubMed Central]

55. Qu X, Sheng H. Stem Cell Therapy for Traumatic Brain Injury: A Progress Update. Ann Neurol Surg. 2018;2(1):1008. http://www.remedypublications.com/annals-of-neurological-surgery-abstract.php?aid=5268

56. ClinicalTrials.gov [database on the Internet]. A service of the U.S. National Institutes of Health [Internet; cited 2019 Dec 20]. Available from: https://www.clinicaltrials.gov/

57. Sun D, Bullock MR, McGinn MJ, Zhou Z, Altememi N, Hagood S, Hamm R, Colello RJ. Basic fibroblast growth factor-enhanced neurogenesis contributes to cognitive recovery in rats following traumatic brain injury. Exp Neurol. 2009 Mar;216(1):56-65. [CrossRef] [PubMed] [PubMed Central]

58. Sun D, Bullock MR, Altememi N, Zhou Z, Hagood S, Rolfe A, McGinn MJ, Hamm R, Colello RJ. The effect of epidermal growth factor in the injured brain after trauma in rats. J Neurotrauma. 2010 May;27(5):923-38. [CrossRef] [PubMed] [PubMed Central]

59. Kleindienst A, McGinn MJ, Harvey HB, Colello RJ, Hamm RJ, Bullock MR. Enhanced hippocampal neurogenesis by intraventricular S100B infusion is associated with improved cognitive recovery after traumatic brain injury. J Neurotrauma. 2005 Jun;22(6):645-55. [CrossRef] [PubMed]

60. Lee C, Agoston DV. Vascular endothelial growth factor is involved in mediating increased de novo hippocampal neurogenesis in response to traumatic brain injury. J Neurotrauma. 2010 Mar;27(3):541-53. [CrossRef] [PubMed]

61. Thau-Zuchman O, Shohami E, Alexandrovich AG, Leker RR. Vascular endothelial growth factor increases neurogenesis after traumatic brain injury. J Cereb Blood Flow Metab. 2010 May;30(5):1008-16. [CrossRef] [PubMed] [PubMed Central]

62. Lu D, Mahmood A, Qu C, Goussev A, Schallert T, Chopp M. Erythropoietin enhances neurogenesis and restores spatial memory in rats after traumatic brain injury. J Neurotrauma. 2005 Sep;22(9):1011-7. [CrossRef] [PubMed]

63. Lu D, Qu C, Goussev A, Jiang H, Lu C, Schallert T, Mahmood A, Chen J, Li Y, Chopp M. Statins increase neurogenesis in the dentate gyrus, reduce delayed neuronal death in the hippocampal CA3 region, and improve spatial learning in rat after traumatic brain injury. J Neurotrauma. 2007 Jul;24(7):1132-46. [CrossRef] [PubMed] [PubMed Central]

64. Xiong Y, Mahmood A, Meng Y, Zhang Y, Qu C, Schallert T, Chopp M. Delayed administration of erythropoietin reducing hippocampal cell loss, enhancing angiogenesis and neurogenesis, and improving functional outcome following traumatic brain injury in rats: comparison of treatment with single and triple dose. J Neurosurg. 2010 Sep;113(3):598-608. [CrossRef] [PubMed] [PubMed Central]

65. Barha CK, Ishrat T, Epp JR, Galea LA, Stein DG. Progesterone treatment normalizes the levels of cell proliferation and cell death in the dentate gyrus of the hippocampus after traumatic brain injury. Exp Neurol. 2011 Sep;231(1):72-81. [CrossRef] [PubMed] [PubMed Central]

66. Han X, Tong J, Zhang J, Farahvar A, Wang E, Yang J, Samadani U, Smith DH, Huang JH. Imipramine treatment improves cognitive outcome associated with enhanced hippocampal neurogenesis after traumatic brain injury in mice. J Neurotrauma. 2011 Jun;28(6):995-1007. [CrossRef] [PubMed] [PubMed Central]

67. Bregy A, Nixon R, Lotocki G, Alonso OF, Atkins CM, Tsoulfas P, Bramlett HM,Dietrich WD. Posttraumatic hypothermia increases doublecortin expressing neurons in the dentate gyrus after traumatic brain injury in the rat. Exp Neurol. 2012 Feb;233(2):821-8. [CrossRef] [PubMed] [PubMed Central]

68. Kovesdi E, Gyorgy AB, Kwon SK, Wingo DL, Kamnaksh A, Long JB, Kasper CE, Agoston DV. The effect of enriched environment on the outcome of traumatic brain injury; a behavioral, proteomics, and histological study. Front Neurosci. 2011 Apr 1;5:42. [CrossRef] [PubMed] [PubMed Central]

69. Cox CS Jr, Hetz RA, Liao GP, Aertker BM, Ewing-Cobbs L, Juranek J, Savitz SI, Jackson ML, Romanowska-Pawliczek AM, Triolo F, Dash PK, Pedroza C, Lee DA, Worth L, Aisiku IP, Choi HA, Holcomb JB, Kitagawa RS. Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells. Stem Cells. 2017 Apr;35(4):1065-1079. [CrossRef] [PubMed] [PubMed Central]

70. Cox CS Jr, Baumgartner JE, Harting MT, Worth LL, Walker PA, Shah SK, Ewing-Cobbs L, Hasan KM, Day MC, Lee D, Jimenez F, Gee A. Autologous bone marrow mononuclear cell therapy for severe traumatic brain injury in children. Neurosurgery. 2011 Mar;68(3):588-600. [CrossRef] [PubMed]

71. Liao GP, Harting MT, Hetz RA, Walker PA, Shah SK, Corkins CJ, Hughes TG, Jimenez F, Kosmach SC, Day MC, Tsao K, Lee DA, Worth LL, Baumgartner JE, Cox CS Jr. Autologous bone marrow mononuclear cells reduce therapeutic intensity for severe traumatic brain injury in children. Pediatr Crit Care Med. 2015 Mar;16(3):245-55. [CrossRef] [PubMed] [PubMed Central]

72. Jethani Z. Can Stem Cells Repair Traumatic Brain Injury? [Internet]; 2018. Available from: https://www.pacificneuroscienceinstitute.org/blog/brain-trauma/can-stem-cells-repair-traumatic-brain-injury/

73. Tian C, Wang X, Wang X, Wang L, Wang X, Wu S, Wan Z. Autologous bone marrow mesenchymal stem cell therapy in the subacute stage of traumatic brain injury by lumbar puncture. Exp Clin Transplant. 2013 Apr;11(2):176-81. [CrossRef] [PubMed]

74. Sharma A, Sane H, Kulkarni P, Yadav J, Gokulchandran N, Biju H, Badhe P. Cell therapy attempted as a novel approach for chronic traumatic brain injury – a pilot study. Springerplus. 2015 Jan 17;4:26. [CrossRef] [PubMed] [PubMed Central]

75. Zhang ZX, Guan LX, Zhang K, Zhang Q, Dai LJ. A combined procedure to deliver autologous mesenchymal stromal cells to patients with traumatic brain injury. Cytotherapy. 2008;10(2):134-9. [CrossRef] [PubMed]

76. Wang S, Cheng H, Dai G, Wang X, Hua R, Liu X, Wang P, Chen G, Yue W, An Y. Umbilical cord mesenchymal stem cell transplantation significantly improves neurological function in patients with sequelae of traumatic brain injury. Brain Res. 2013 Sep 26;1532:76-84. [CrossRef] [PubMed]

Published

2020-03-12

How to Cite

Liubich, L. D., & Egorova, D. M. (2020). Stem cells application for the treatment of traumatic brain injury. Ukrainian Neurosurgical Journal, 26(1), 20–29. https://doi.org/10.25305/unj.189596

Issue

Section

Review articles