Combinatorial strategies for cell transplantation in traumatic spinal cord injury.

Vipin Jagrit, Jacob Koffler, Jennifer N Dulin
Author Information
  1. Vipin Jagrit: Department of Biology, Texas A&M University, College Station, TX, United States.
  2. Jacob Koffler: Department of Neurosciences, University of California, San Diego, La Jolla, CA, United States.
  3. Jennifer N Dulin: Department of Biology, Texas A&M University, College Station, TX, United States.

Abstract

Spinal cord injury (SCI) substantially reduces the quality of life of affected individuals. Recovery of function is therefore a primary concern of the patient population and a primary goal for therapeutic interventions. Currently, even with growing numbers of clinical trials, there are still no effective treatments that can improve neurological outcomes after SCI. A large body of work has demonstrated that transplantation of neural stem/progenitor cells (NSPCs) can promote regeneration of the injured spinal cord by providing new neurons that can integrate into injured host neural circuitry. Despite these promising findings, the degree of functional recovery observed after NSPC transplantation remains modest. It is evident that treatment of such a complex injury cannot be addressed with a single therapeutic approach. In this mini-review, we discuss combinatorial strategies that can be used along with NSPC transplantation to promote spinal cord regeneration. We begin by introducing bioengineering and neuromodulatory approaches, and highlight promising work using these strategies in integration with NSPCs transplantation. The future of NSPC transplantation will likely include a multi-factorial approach, combining stem cells with biomaterials and/or neuromodulation as a promising treatment for SCI.

Keywords

References

  1. Nat Med. 2019 Feb;25(2):263-269 [PMID: 30643285]
  2. Neurosci Res. 2012 Mar;72(3):199-213 [PMID: 22192467]
  3. Anat Cell Biol. 2015 Jun;48(2):104-13 [PMID: 26140221]
  4. Exp Neurol. 2020 May;327:113208 [PMID: 31962127]
  5. Nat Med. 2023 Nov;29(11):2854-2865 [PMID: 37932548]
  6. J Neurotrauma. 2018 Aug 1;35(15):1781-1799 [PMID: 29295654]
  7. EMBO Mol Med. 2020 Mar 6;12(3):e11505 [PMID: 32090481]
  8. J Neurosci Res. 2007 Aug 1;85(10):2138-46 [PMID: 17520747]
  9. Int J Mol Sci. 2023 Jan 03;24(1): [PMID: 36614259]
  10. Nat Methods. 2018 Sep;15(9):723-731 [PMID: 30082899]
  11. Cell. 2012 Sep 14;150(6):1264-73 [PMID: 22980985]
  12. Ther Innov Regul Sci. 2019 Jan;53(1):120-127 [PMID: 29756484]
  13. Nat Med. 2016 May;22(5):479-87 [PMID: 27019328]
  14. J Neurotrauma. 2021 May 1;38(9):1251-1266 [PMID: 33353467]
  15. PLoS One. 2015 Jul 24;10(7):e0133998 [PMID: 26207623]
  16. Behav Brain Res. 2012 Jun 15;232(1):245-51 [PMID: 22537774]
  17. Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):14069-74 [PMID: 16172374]
  18. Lancet. 2017 May 6;389(10081):1821-1830 [PMID: 28363483]
  19. Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14662-7 [PMID: 18787118]
  20. J Neural Eng. 2018 Apr;15(2):025004 [PMID: 29303112]
  21. Cell Rep. 2021 Nov 23;37(8):110019 [PMID: 34818559]
  22. Spine J. 2024 Mar;24(3):534-553 [PMID: 37871660]
  23. Expert Rev Neurother. 2017 May;17(5):433-440 [PMID: 27927055]
  24. Exp Neurol. 2010 Apr;222(2):211-8 [PMID: 20059998]
  25. Cell Biosci. 2023 Jan 9;13(1):4 [PMID: 36624495]
  26. Lancet. 2011 Jun 4;377(9781):1938-47 [PMID: 21601270]
  27. Sci Rep. 2016 Aug 03;6:30898 [PMID: 27485458]
  28. J Biomed Mater Res A. 2020 Aug 1;108(8):1617-1633 [PMID: 32196949]
  29. Exp Ther Med. 2017 Oct;14(4):3355-3368 [PMID: 29042919]
  30. Neurol Res. 2006 Jul;28(5):474-81 [PMID: 16808875]
  31. Stem Cells. 2019 Jan;37(1):6-13 [PMID: 30371964]
  32. Science. 1982 Jan 8;215(4529):174-6 [PMID: 7031899]
  33. Biomaterials. 2021 Aug;275:120982 [PMID: 34214785]
  34. Neuromodulation. 2017 Apr;20(3):206-214 [PMID: 28371170]
  35. Proc Natl Acad Sci U S A. 1989 Feb;86(3):933-7 [PMID: 2915988]
  36. Neurochem Int. 2021 Mar;144:104973 [PMID: 33497713]
  37. Eur Cell Mater. 2003 May 20;5:1-16; discussion 16 [PMID: 14562275]
  38. Cell Transplant. 2010;19(1):89-101 [PMID: 19818206]
  39. J Rehabil Med. 2016 Jul 18;48(7):589-96 [PMID: 27292455]
  40. World J Urol. 2000 Feb;18(1):2-9 [PMID: 10766037]
  41. Neural Regen Res. 2020 Aug;15(8):1437-1450 [PMID: 31997803]
  42. Exp Neurol. 2010 Sep;225(1):231-6 [PMID: 20599981]
  43. J Vis Exp. 2018 Apr 13;(134): [PMID: 29708538]
  44. Biomater Res. 2022 Nov 22;26(1):63 [PMID: 36414973]
  45. Cells. 2020 Sep 17;9(9): [PMID: 32957463]
  46. Phys Med Rehabil Clin N Am. 2014 Aug;25(3):631-54, ix [PMID: 25064792]
  47. Neural Regen Res. 2019 Jan;14(1):69-71 [PMID: 30531075]
  48. Stem Cells. 2007 Feb;25(2):419-24 [PMID: 17053214]
  49. Nat Rev Neurosci. 2006 Aug;7(8):628-43 [PMID: 16858391]
  50. Int J Biol Macromol. 2011 Oct 1;49(3):247-54 [PMID: 21635916]
  51. Biomaterials. 2012 Jun;33(19):4783-91 [PMID: 22483241]
  52. Nat Med. 2022 Feb;28(2):260-271 [PMID: 35132264]
  53. Mayo Clin Proc. 2017 Apr;92(4):544-554 [PMID: 28385196]
  54. Neuromodulation. 2018 Jul;21(5):457-465 [PMID: 29608229]
  55. J Neurosci Res. 2002 Jun 1;68(5):501-10 [PMID: 12111840]
  56. NPJ Regen Med. 2021 Oct 20;6(1):66 [PMID: 34671050]
  57. Stem Cells Transl Med. 2023 Apr 17;12(4):207-214 [PMID: 36892546]
  58. Front Cell Neurosci. 2022 Sep 07;16:977679 [PMID: 36212690]
  59. Exp Neurol. 2016 Apr;278:22-6 [PMID: 26808660]
  60. J Neurotrauma. 2019 Aug 1;36(15):2325-2336 [PMID: 30667299]
  61. Brain. 2014 May;137(Pt 5):1394-409 [PMID: 24713270]
  62. Ultrasound Med Biol. 2019 Jul;45(7):1509-1536 [PMID: 31109842]
  63. Nature. 2023 Jun;618(7963):126-133 [PMID: 37225984]
  64. Nat Med. 2018 May;24(4):484-490 [PMID: 29480894]
  65. Signal Transduct Target Ther. 2021 Mar 19;6(1):122 [PMID: 33737507]
  66. Anesthesiology. 2010 Dec;113(6):1265-7 [PMID: 21042195]
  67. Ann Biomed Eng. 2014 Jul;42(7):1517-27 [PMID: 24402648]
  68. J Neurotrauma. 2018 May 1;35(9):1069-1078 [PMID: 29279015]
  69. Biomaterials. 2021 Jan;268:120596 [PMID: 33341040]
  70. Nat Rev Neurosci. 2020 Jul;21(7):366-383 [PMID: 32518349]
  71. Science. 2009 Jun 26;324(5935):1673-7 [PMID: 19556500]
  72. Nat Med. 2019 Jun;25(6):898-908 [PMID: 31160817]
  73. J Neurotrauma. 2006 May;23(5):617-34 [PMID: 16689666]
  74. Cell Stem Cell. 2016 Oct 6;19(4):544-557 [PMID: 27666009]
  75. Tissue Eng Part A. 2009 Jul;15(7):1797-805 [PMID: 19191513]
  76. Bioact Mater. 2017 Dec 01;3(3):278-314 [PMID: 29744467]
  77. J Neurosci. 2011 Mar 23;31(12):4675-86 [PMID: 21430166]
  78. Nat Med. 2018 Nov;24(11):1677-1682 [PMID: 30250140]
  79. Adv Exp Med Biol. 2018;1064:161-180 [PMID: 30471032]
  80. Neurosurgery. 2016 Nov;79(5):667-677 [PMID: 27584814]
  81. J Biomed Sci. 2009 Nov 25;16:108 [PMID: 19939265]
  82. Neuromodulation. 2014 Aug;17(6):515-50; discussion 550 [PMID: 25112889]
  83. Neuromodulation. 2018 Jan;21(1):56-66 [PMID: 28961366]
  84. Biomaterials. 2023 Jun;297:122103 [PMID: 37028111]
  85. Neural Regen Res. 2019 Aug;14(8):1352-1363 [PMID: 30964053]
  86. Sci Rep. 2017 Oct 26;7(1):13476 [PMID: 29074997]
  87. Exp Neurol. 2014 Jan;251:47-57 [PMID: 24192152]
  88. Biomaterials. 2017 Oct;142:31-40 [PMID: 28719819]
  89. Nat Med. 1999 Dec;5(12):1410-2 [PMID: 10581084]
  90. J Cell Physiol. 2008 Apr;215(1):129-39 [PMID: 17941084]
  91. NPJ Regen Med. 2020 Jun 15;5:12 [PMID: 32566251]
  92. Stem Cells Transl Med. 2014 Oct;3(10):1148-59 [PMID: 25107585]
  93. Regen Ther. 2021 Sep 07;18:321-333 [PMID: 34522725]
  94. Stem Cell Reports. 2022 Jan 11;17(1):127-142 [PMID: 35021049]
  95. Biomaterials. 2016 Mar;83:23-36 [PMID: 26773663]
  96. Stem Cell Reports. 2018 Dec 11;11(6):1433-1448 [PMID: 30472009]
  97. J Neurotrauma. 2018 Dec 15;35(24):2883-2903 [PMID: 29873284]
  98. Nature. 1980 Mar 20;284(5753):264-5 [PMID: 7360259]
  99. Sci Adv. 2023 Feb 10;9(6):eade8829 [PMID: 36753555]
  100. Exp Neurol. 2002 Oct;177(2):360-75 [PMID: 12429183]

Word Cloud

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