Skip to main content

Effect of Implantation of a Fibrin Matrix Associated with Neonatal Brain Cells on the Course of an Experimental Spinal Cord Injury

Abstract

The effect of immediate implantation of a fibrin matrix associated with allogeneic neonatal rat brain cells on their motor function recovery after a spinal cord injury (SCI) was studied. The cohorts of animals selected for the study were represented by white adult outbred rats (approximately 260 g each, 4 or 5 months old). The SCI simulation was based on a left-side hemisection of the spinal cord at the level of approximately T13–L1 segments. The rehabilitation treatment included immediate transplantation of a human fibrin matrix associated with neonatal rat brain cells (NBCs) (n = 9) into the injury area. The reference groups were represented by animals with isolated traumatic (Tr) SCIs (n = 7) and those with implantation of a human acellular fibrin (Fb) matrix (n = 6) into the injury area. The motor activity was assessed in the paretic hindlimb on the Basso, Beattie, and Bresnahan (BBB) scale; spasticity was evaluated on the Ashworth scale; and the pathohistological examination of longitudinal spinal cord sections sampled in the remote posttraumatic period was performed using the silver impregnation staining method. The fibrin matrix promotes viability, growth, and differentiation in the incorporated neonatal rat brain cells. Starting from the second or third week after the implantation into the injury epicenter, the motor function in the paretic limb corresponded to approximately 11 points in the Fb and NBC groups and to approximately six points in the Tr group on the BBB locomotor scale. No significant differences in the locomotor function of the paretic limb were recorded throughout the entire experiment between the NBC and Fb groups nor between the Fb and Tr groups. Significant differences between the NBC and Tr groups were recorded from the second, fourth, and eighth week, as well as the third and fifth months, post injury. A significant prevalence in the level of spasticity in the Tr group over the NBC and Fb groups was recorded, respectively, from the sixth and the seventh week after the injury. An immediate implantation of the fibrin matrix in complex with allogeneic neonatal brain cells or without the latter causes a significant positive effect on the motor function recovery after a lacerative SCI.

This is a preview of subscription content, access via your institution.

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.

REFERENCES

  1. Abbaszadeh, H.-A., Tiraihi, T., Delshad, A., et al., Differentiation of neurosphere-derived rat neural stem cells into oligodendrocyte-like cells by repressing PDGF-α and Olig2 with triiodothyronine, Tissue Cell, 2014, vol. 46, no. 6, pp. 462–469. https://doi.org/10.1016/j.tice.2014.08.003

    CAS  Article  PubMed  Google Scholar 

  2. Amable, P.R., Carias, R.B.V., Teixeira, M.V.T., et al., Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors, Stem Cell Res. Ther., 2013, vol. 4, no. 3, art. ID 67. https://doi.org/10.1186/scrt218

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. Arvanian, V.L., Schnell, L., Lou, L., et al., Chronic spinal hemisection in rats induces a progressive decline in transmission in uninjured fibers to motoneurons, Exp. Neurol., 2009, vol. 216, no. 2, pp. 471–480. https://doi.org/10.1016/j.expneurol.2009.01.004

    Article  PubMed  PubMed Central  Google Scholar 

  4. Assinck, P., Duncan, G.J., Hilton, B.J., et al., Cell transplantation therapy for spinal cord injury, Nat. Neurosci., 2017, vol. 20, no. 5, pp. 637–647. https://doi.org/10.1016/j.stemcr.2020.05.017

    CAS  Article  PubMed  Google Scholar 

  5. Basso, D.M., Beattie, M.S., and Bresnahan, J.C., A sensitive and reliable locomotor rating scale for open field testing in rats, J. Neurotrauma, 1995, vol. 12, no. 1, pp. 1–21. https://doi.org/10.1089/neu.1995.12.1

    CAS  Article  PubMed  Google Scholar 

  6. Bento, A.R., Quelhas, P., Oliveira, M.J., et al., Three-dimensional culture of single embryonic stem-derived neural/stem progenitor cells in fibrin hydrogels: neuronal network formation and matrix remodeling, J. Tissue Eng. Regen. Med., 2017, vol. 11, no. 12, pp. 3494–3507. https://doi.org/10.1002/term.2262

    CAS  Article  PubMed  Google Scholar 

  7. Blesch, A. and Tuszynski, M.H., Spinal cord injury: plasticity, regeneration and the challenge of translational drug development, Trends Neurosci., 2009, vol. 32, no. 1, pp. 41–47. https://doi.org/10.1016/j.tins.2008.09.008

    CAS  Article  PubMed  Google Scholar 

  8. Brown, A. and Martinez, M., From cortex to cord: motor circuit plasticity after spinal cord injury, Neural Regener. Res., 2019, vol. 14, no. 12, pp. 2054–2062. https://doi.org/10.4103/1673-5374.262572

    Article  Google Scholar 

  9. Burns, A.S., Marino, R.J., Kalsi-Ryan, S., Middleton, J.W., Tetreault, L.A., Dettori, J.R., Mihalovich, K.E., and Fehlings, M.G., Type and timing of rehabilitation following acute and subacute spinal cord injury: a systematic review, Global Spine J., 2017, vol. 7, no. 3, 175–194. https://doi.org/10.1177/2192568217703084

    Article  Google Scholar 

  10. Cargnello, M. and Roux, P.P., Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases, Mol. Biol. Rev., 2011, vol. 75, no. 1, pp. 50–83. https://doi.org/10.1128/MMBR.00031-10

    CAS  Article  Google Scholar 

  11. Carlson, S.W. and Saatman, K.E., Central infusion of IGF-1 increases hyppocampal neurogenesis and improves neurobehavioral function following traumatic brain injury, J. Neurotrauma, 2018, vol. 35, no. 13, pp. 1467–1480. https://doi.org/10.1089/neu.2017.5374

    Article  PubMed  PubMed Central  Google Scholar 

  12. Carriel, V., Garrido-Gomez, J., Hernandez-Cortes, P., et al., Combination of fibrin-agarose hydrogels and adipose-derived mesenchymal stem cells for peripheral nerve regeneration, J. Neural Eng., 2013, vol. 10, no. 2, art. ID 026022. https://doi.org/10.1088/1741-2560/10/2/026022

    Article  PubMed  Google Scholar 

  13. Carriel, V., Scionti, G., Campos, F., et al., In vitro characterization of a nanostructered fibrin agarose bio-artificial nerve substitute, J. Tissue Eng. Regener. Med., 2015, vol. 11, no. 5, pp. 1412–1426. https://doi.org/10.1002/term.2039

    CAS  Article  Google Scholar 

  14. Cizkova, D., Murgoci, A.N., and Cubinkova, V., Spinal cord injury: animal models, imaging tools and the treatment strategies, Neurochem. Res., 2020, vol. 45, no. 1, pp. 134–143. https://doi.org/10.1007/s11064-019-02800-w

    CAS  Article  PubMed  Google Scholar 

  15. Cliffer, K.D., Tonra, J.R., Carson, S.R., et al., Consistent repeated M- and H-wave recording in the hind limb of rats, Muscle Nerve, 1998, vol. 21, no. 11, pp. 1405–1413. https://doi.org/10.1002/(sici)1097-4598(199811)21:11<1405::aidmus7>3.0.co;2-d

    CAS  Article  PubMed  Google Scholar 

  16. D’Amico, J.M., Condliffe, E.G., Martins, K.J., et al., Recovery of neuronal and network excitability after spinal cord injury and implications for spasticity, Front. Integr. Neurosci., 2014, vol. 8, art. ID 36. https://doi.org/10.3389/fnint.2014.00036

    Article  PubMed  PubMed Central  Google Scholar 

  17. DeVivo, M.J., Epidemiology of traumatic spinal cord injury: trends and future implications, Spinal Cord, 2012, vol. 50, no. 5, pp. 365–372. https://doi.org/10.1038/sc.2011.178

    CAS  Article  PubMed  Google Scholar 

  18. Dietz, V. and Schwab, M.E., From the rodent spinal cord injury model to human application: promises and challenges, J. Neurotrauma., 2017, vol. 34, no. 9, pp. 1826–1830. https://doi.org/10.1089/neu.2016.4513

    Article  PubMed  Google Scholar 

  19. Dijkers, M.P., Akers, K.G., and Dieffenbach, S., Systematic reviews of clinical benefits of exoskeleton use for gait and mobility in neurologic disorders: a tertiary study, Arch. Phys. Med. Rehabil., 2021, vol. 102, no. 2, pp. 300–313. https://doi.org/10.1016/j.apmr.2019.01.025

    Article  PubMed  Google Scholar 

  20. Dong, H.W., Wang, L.H., Zhang, M., et al., Decreased dynorphin A (1–17) in the spinal cord of spastic rats after the compressive injury, Brain Res. Bull., 2005, vol. 67, no. 3, pp. 189–195. https://doi.org/10.1016/j.brainresbull.2005.06.026

    CAS  Article  PubMed  Google Scholar 

  21. Finnerup, N.B., Norrbrink, C., Trok, K., et al., Phenotypes and predictors of pain following traumatic spinal cord injury: a prospective study, J. Pain, 2014, vol. 15, no. 1, pp. 40–48. https://doi.org/10.1016/j.jpain.2013.09.008

    Article  PubMed  Google Scholar 

  22. Flynn, J.R., Graham, B.A., Galea, M.P., et al., The role of propriospinal interneurons in recovery from spinal cord injury, Neuropharmacology, 2011, vol. 60, no. 5, pp. 809–822. https://doi.org/10.1016/j.neuropharm.2011.01.016

    CAS  Article  PubMed  Google Scholar 

  23. Garcia, E., Aguilar-Cevallos, J., Silva-Garcia, R., et al., Cytokine and growth factor activation in vivo and in vitro after spinal cord injury, Mediators Inflammation, 2016, vol. 2016, art. ID 9476020. https://doi.org/10.1155/2016/9476020

    CAS  Article  Google Scholar 

  24. GBD 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators, Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: a systematic analysis for the Global Burden of Disease Study, Lancet Neurol., 2019, vol. 18, no. 1, pp. 56–87. https://doi.org/10.1016/S1474-4422(18)30415-0

  25. Gilerovich, E.G., Moshonkina, T.R., Fedorova, E.A., et al., Morphofunctional characteristics of the lumbar enlargement of the spinal cord in rats, Neurosci. Behav. Physiol., 2008, vol. 38, no. 8, pp. 855–860. https://doi.org/10.1007/s11055-008-9056-8

    CAS  Article  PubMed  Google Scholar 

  26. Gonzalez-Perez, O., Romero-Rodriguez, R., Soriano-Navarro, M., et al., Epidermal growth factor induces the progeny of subventricular zone type B cells to migrate and differentiate into oligodendrocytes, Stem Cells, 2009, vol. 27, no. 8, pp. 2032–2043. https://doi.org/10.1002/stem.119

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. Hamid, R., Averbeck, M.A., Chiang, H., et al., Epidemiology and pathophysiology of neurogenic bladder after spinal cord injury, World J. Urol., 2018, vol. 36, no. 10, pp. 1517–1527. https://doi.org/10.1007/s00345-018-2301-z

    Article  PubMed  Google Scholar 

  28. Hill, R.A., Patel, K.D., Medved, J., et al., NG2 cells in white matter but not gray matter proliferate in response to PDGF, J. Neurosci., 2013, vol. 33, no. 36, pp. 14558–14566. https://doi.org/10.1523/JNEUROSCI.2001-12.2013

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. Holtz, K.A., Lipson, R., Noonan, V.K., et al., Prevalence and effect of problematic spasticity after traumatic spinal cord injury, Arch. Phys. Med. Rehabil., 2017, vol. 98, no. 6, pp. 1132–1138. https://doi.org/10.1016/j.apmr.2016.09.124

    Article  PubMed  Google Scholar 

  30. Hotwani, K. and Sharma, K., Platelet rich fibrin—a novel acumen into regenerative endodontic therapy, Restor. Dent. Endod., 2014, vol. 39, no.1, pp. 1–6. https://doi.org/10.5395/rde.2014.39.1.1

    Article  PubMed  PubMed Central  Google Scholar 

  31. Hsieh, T.H., Tsai, J.Y., Wu, Y.N., et al., Time course quantification of spastic hypertonia following spinal hemisection in rats, Neuroscience, 2010, vol. 167, no. 1, pp. 185–198. https://doi.org/10.1016/j.neuroscience.2010.01.064

    CAS  Article  PubMed  Google Scholar 

  32. Jeong, H.J., Yun, Y., Lee, S.J., et al., Biomaterials and strategies for repairing spinal cord lesions, Neurochem. Int., 2021, vol. 144, art. ID, 104973. https://doi.org/10.1016/j.neuint.2021.104973

  33. Johnson, P.J., Parker, S.R., and Sakiyama-Elbert, S.E., Fibrin-based tissue engineering scaffolds enhance neural fiber sprouting and delay the accumulation of reactive astrocytes at the lesion in a subacute model of spinal cord injury, J. Biomed. Mater. Res., Part A, 2010, vol. 92, no. 1, pp. 152–163. https://doi.org/10.1002/jbm.a.32343

    CAS  Article  Google Scholar 

  34. Khan, S., Mafi, P., Mafi, R., et al., A systematic review of mesenchymal stem cells in spinal cord injury, intervertebral disc repair and spinal fusion, Curr. Stem Cell Res. Ther., 2018, vol. 13, no. 4, pp. 316–323. https://doi.org/10.2174/1574888x11666170907120030

    CAS  Article  PubMed  Google Scholar 

  35. Khorasanizadeh, M., Yousefifard, M., Eskian, M., et al., Neurological recovery following traumatic spinal cord injury: a systematic review and meta-analysis, J. Neurosurg. Spine, 2019, vol. 15, pp. 1–17. https://doi.org/10.3171/2018.10.SPINE 18802

  36. Ko, C.C., Tu, T.H., Wu, J.C., et al., Acidic fibroblast growth factor in spinal cord injury, Neurospine, 2019, vol. 16, no. 4, pp. 728–738. https://doi.org/10.14245/ns.1836216.108

    Article  PubMed  PubMed Central  Google Scholar 

  37. Kolomiytsev, A.K., Chaikovskiy, I.B., and Tereshchenko, T.L., Rapid method of silver nitrate impregnation of elements of the peripheral nervous system suitable for paraffin and celloidin sections, Arkh. Anat., Gistol. Embriol., 1981, vol. 81, no. 8, pp. 93–96.

    Google Scholar 

  38. Kopach, O., Medvediev, V., Krotov, V., et al., Opposite, bidirectional shifts in excitation and inhibition in specific types of dorsal horn interneurons are associated with spasticity and pain post-SCI, Sci. Rep., 2017, vol. 7, no. 1, art. ID 5884. https://doi.org/10.1038/s41598-017-06049-7

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. Lemmon, V.P., Ferguson, A.R., Popovich, P.G., et al., MIASCI Consortium, Minimum information about a spinal cord injury experiment: a proposed reporting standard for spinal cord injury experiments, J. Neurotrauma, 2014, vol. 31, no. 15, vol. 1354–1361. https://doi.org/10.1089/neu.2014.3400

  40. Li, J.A., Zhao, C.F., Li, S.J. et al., Modified insulinlike growth factor 1 containing collagen-binding domain for nerve regeneration, Neural Regener. Res., 2018, vol. 13, no. 2, pp. 298–303. https://doi.org/10.4103/1673-5374.226400

    CAS  Article  Google Scholar 

  41. Li, L.S., Yu, H., Raynald, R., et al., Anatomical mechanism of spontaneous recovery in regions caudal to thoracic spinal cord injury lesions in rats, PeerJ., 2017, vol. 5, art. ID e2865. https://doi.org/10.7717/peerj.2865

    Article  PubMed  PubMed Central  Google Scholar 

  42. Lin, L., Lin, H., Bai, S., et al., Bone marrow mesenchymal stem cells (BMSCs) improved functional recovery of spinal cord injury partly by promoting axonal regeneration, Neurochemistry, 2018, vol. 115, pp. 80–84. https://doi.org/10.1016/j.neuint.2018.02.007

    CAS  Article  Google Scholar 

  43. Litvinov, R.I., Gorkun, O.V., Owen, S.F., et al., Polymerization of fibrin: specificity, strength, and stability of knob-hole interactions studied at the single-molecule level, Blood, 2005, vol. 106, no. 9, pp. 2944–2951. https://doi.org/10.1182/blood-2005-05-2039

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. Liu, S., Schackel, T., Weidner, N., and Puttagunta, R., Biomaterial-supported cell transplantation treatments for spinal cord injury: challenges and perspectives, Front. Cell. Neurosci., 2018, vol. 11, art. ID 430. https://doi.org/10.3389/fncel.2017.00430

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. Liu, S., Xie, Y.Y., and Wang, B., Role and prospects of regenerative biomaterials in the repair of spinal cord injury, Neural Regener. Res., 2019, vol. 14, no. 8, pp. 1352–1363. https://doi.org/10.4103/1673-5374.253512

    Article  Google Scholar 

  46. Lu, P., Wang, Y., Graham, L. et al., Long-distance growth and connectivity of neural stem cells after severe spinal cord injury, Cell, 2012, vol. 150, no. 6, pp. 1264–1273. https://doi.org/10.1016/j.cell.2012.08.020

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. Lu, P., Grahman, L., Wang, Y., et al., Promotion of survival and differentiation of neural stem cells with fibrin and growth factor coctails after severe spinal cord injury, J. Visualized Exp., 2014, vol. 89, art. ID e50641. https://doi.org/10.3791/50641

    CAS  Article  Google Scholar 

  48. Majczynski, H. and Slawinska, U., Locomotor recovery after thoracic spinal cord lesions in cats, rats and humans, Acta Neurobiol. Exp., 2007, vol. 67, no. 3, pp. 235–257.

    Google Scholar 

  49. Metz, G.A., Merkler, D., Dietz, V., et al., Efficient testing of motor function in spinal cord injured rats, Brain Res., 2000, vol. 883, no. 2, pp. 165–177. https://doi.org/10.1016/s0006-8993 (00)02778-5

  50. Mills, C.D., Hains, B.C., Johnson, K.M., et al., Strain and model differences in behavioral outcomes after spinal cord injury in rat, J. Neurotrauma, 2001, vol. 18, no. 8, pp. 743– 756. https://doi.org/10.1089/089771501316919111

    CAS  Article  PubMed  Google Scholar 

  51. Moonen, G., Satkunendrarajah, K., Wilcox, J.T., et al., A New acute impact-compression lumbar spinal cord injury model in the rodent, J. Neurotrauma, 2016, vol. 33, no. 3, pp. 278–289. https://doi.org/10.1089/neu.2015.3937

    Article  PubMed  PubMed Central  Google Scholar 

  52. Muheremu, A., Peng, J., and Ao, Q., Stem cell based therapies for spinal cord injury, Tissue Cell, 2016, vol. 48, no. 4, pp. 328–333. https://doi.org/10.1016/j.tice.2016.05.008

    Article  PubMed  Google Scholar 

  53. Muller, Ì.F., Ris, I., and Ferry, J.D., Electron microscopy of fine fibrin clots and fine and coarse fibrin films. Observations of fibers in cross-section and in deformed states, J. Mol. Biol., 1984, vol. 174, no. 2, pp. 369–384. https://doi.org/10.1016/0022-2836(84)90343-7

    CAS  Article  PubMed  Google Scholar 

  54. Oliveri, R.S., Bello, S., and Biering-Sørensen, F., Mesenchymal stem cells improve locomotor recovery in traumatic spinal cord injury: systematic review with meta-analyses of rat models, Neurobiol. Dis., 2014, vol. 62, pp. 338–353. https://doi.org/10.1016/j.nbd.2013.10.014

    CAS  Article  PubMed  Google Scholar 

  55. Olude, M.A., Mustapha, O.A., Ogunbunmi, T.K., et al., The vertebral column, ribs, and sternum of the African giant rat (Cricetomys gambianus Waterhouse), Sci. World J., 2013, vol. 2013, art. ID 973537. https://doi.org/10.1155/2013/973537

    Article  Google Scholar 

  56. Ozturk, A.M., Sozbilen, M.C., Sevgili, E., et al., Epidermal growth factor regulate apoptosis and oxidative stress in a rat model of spinal cord injury, Injury, 2018, vol. 49, no. 6, pp. 1038–1045. https://doi.org/10.1016/j.injury.2018.03.021

    Article  PubMed  Google Scholar 

  57. Özkan, Z.E., Macro-anatomical investigations on the skeletons of mole-rat (Spalax leucodon Nordmann) III. Skeleton axiale, Vet. Arhiv, 2007, vol. 77, pp. 281–289.

    Google Scholar 

  58. Park, M.N., Lee, J.Y., Jeong, M.S., et al., The roll of Purkinje cell-derived VEGF in cerebellar astrogliosis in Niemann-Pick type C mice, BMB Rep., 2018, vol. 51, no. 2, pp. 79– 84. https://doi.org/10.5483/bmbrep.2018.51.2.168

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  59. Pertici, V., Amendola, J., Laurin, J., et al., The use of poly(N-(2-hydroxypropyl)-methacrylamide) hydrogel to repair a T10 spinal cord hemisection in rat: a behavioural, electrophysiological and anatomical examination, ASN Neuro, 2013, vol. 5, no. 2, art. ID e00114. https://doi.org/10.1042/AN20120082

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  60. Pretz, C.R., Kozlowski, A.J., Chen, Y., et al., Trajectories of life satisfaction after spinal cord injury, Arch. Phys. Med. Rehabil., 2016, vol. 97, no. 10, pp. 1706–1713. https://doi.org/10.1016/j.apmr.2016.04.022

    Article  PubMed  Google Scholar 

  61. Robinson, J. and Lu, P., Optimization of trophic support for stem cell graft in sites of spinal cord injury, Exp. Neurol., 2017, vol. 291, pp. 87–97. https://doi.org/10.1016/j.exp neurol.2017.02.007

  62. Rao, S.N. and Pearse, D.D., Regulating axonal responses to injury: the intersection between signaling pathways involved in axon myelination and the inhibition of axon regeneration, Front. Mol. Neurosci., 2016, vol. 9, art. ID 33.https://doi.org/10.3389/fnmol.2016.00033

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  63. Sachdeva, R., Gao, F., Chan, C.C.H., and Krassioukov, A.V., Cognitive function after spinal cord injury: a systematic review, Neurology, 2018, vol. 91, no. 13, pp. 611–621. https://doi.org/10.1212/WNL.0000000000006244

    Article  PubMed  PubMed Central  Google Scholar 

  64. Schuh, C.M., Morton, T.J., Banerjee, A., et al., Activation of Schwann cell-like cells on aligned fibrinpoly (lactic-co-glycolic acid) structures: a novel construct for application in peripheral nerve regeneration, Cells Tissues Organs, 2015, vol. 200, no. 5, pp. 287–299. https://doi.org/10.1159/000437091

    CAS  Article  PubMed  Google Scholar 

  65. Shah, M., Peterson, C., and Yilmaz, E., Current advancements in the management of spinal cord injury: a comprehensive review of literature, Surg. Neurol. Int., 2020, vol. 11, art. ID. 2. https://doi.org/10.25259/SNI_568_2019

  66. Singh, A., Tetreault, L., Kalsi-Ryan, S., et al., Global prevalence and incidence of traumatic spinal cord injury, Clin. Epidemiol., 2014, vol. 23, no. 6, pp. 309–331. https://doi.org/10.2147/CLEP.S68889

    Article  Google Scholar 

  67. Steeves, J.D., Bench to bedside: challenges of clinical translation, Prog. Brain Res., 2015, vol. 218, pp. 227–239. https://doi.org/10.1016/bs.pbr.2014.12.008

    Article  PubMed  Google Scholar 

  68. Swieck, K., Conta-Steencken, A., Middleton, F.A., et al., Effect of lesion proximity on the regenerative response of long descending propriospinal neurons after spinal transection injury, BMC Neurosci., 2019, vol. 20, no. 1, art. ID 10. https://doi.org/10.1186/s12868-019-0491-y

    Article  PubMed  PubMed Central  Google Scholar 

  69. Tatullo, M., Marrelli, M., Cassetta, M., et al., Platelet rich fibrin (P.R.F.) in reconstructive surgery of atrophied maxillary bones: Clinical and histological evaluations, Int. J. Med. Sci., 2012, vol. 9, pp. 872–880. https://doi.org/10.7150/ijms.5119

    Article  PubMed  PubMed Central  Google Scholar 

  70. Tran, A.P., Warren, P.M., Silver, J., et al., The biology of regeneration failure and success after spinal cord injury, Physiol. Rev., 2018, vol. 98, no. 2, pp. 881–917. https://doi.org/10.1152/physrev.00017.2017

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  71. Wan, F.J., Chien, W.C., Chung, C.H., et al., Association between traumatic spinal cord injury and affective and other psychiatric disorders – A nationwide cohort study and effects of rehabilitation therapies, J. Affective Disord., 2020, vol. 265, vol. 381–388. https://doi.org/10.1016/j.jad.2020.01.063

  72. Wang, Y., Tan, H., and Hui, X., Biomaterial scaffolds in regenerative therapy of the central nervous system, Biomed. Res. Int., 2018, vol. 2018, art. ID 784890.1 https://doi.org/10.1155/2018/7848901

  73. Webb, A.A. and Muir, G.D., Compensatory locomotor adjustments of rats with cervical or thoracic spinal cord hemisections, J. Neurotrauma, 2002, vol. 19, no. 2, vol. 239–256. https://doi.org/10.1089/08977150252806983

  74. Yao, S., Liu, X., Yu, S., et al., Co-effects of matrix low elasticity and aligned topography on stem cell neurogenic differentiation and rapid neurite outgrowth, Nanoscale, 2016, vol. 8, no. 19, pp. 10252–10265. https://doi.org/10.1039/c6nr01169a

    CAS  Article  PubMed  Google Scholar 

  75. Zhang, Q., Shi, B., and Ding, J., Polymer scaffolds facilitate spinal cord injury repair, Acta Biomater., 2019, vol. 88, pp. 57–77. https://doi.org/10.1016/j.actbio.2019.01.056

    CAS  Article  PubMed  Google Scholar 

  76. Zhang, Q., Yan, S., You, R., et al., Multichannel silk protein/laminin grafts for spinal cord injury repair, J. Biomed. Mater. Res., Part A, 2016, vol. 104, no. 12, pp. 3045–3057. https://doi.org/10.1002/jbm.a.35851

    CAS  Article  Google Scholar 

  77. Zhao, Y.Y., Yuan, Y., Chen, Y., et al., Histamine promotes locomotion recovery after spinal cord hemisection via inhibiting astrocytic scar formation, CNS Neurosci. Ther., 2015, vol. 21, no. 5, pp. 454–462. https://doi.org/10.1111/cns.12379

Download references

Funding

This study was not supported by any grant from financial establishments of the governmental, commercial, or noncommercial sectors.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to V. V. Medvediev, N. P. Oleksenko, L. D. Pichkur, S. A. Verbovska, S. I. Savosko, N. G. Draguntsova, Yu. A. Lontkovskiy, V. V. Vaslovych or V. I. Tsymbalyuk.

Ethics declarations

Conflict of interests. The authors declare that they have no conflict of interests.

Statement on the welfare of animals. The study observed all standards of bioethics and humane treatment of animals, which were stipulated under the EU Council Directive 86/609/EEC On the Approximation of Laws, Regulations, and Administrative Provisions of the Member States regarding the Protection of Animals Used for Experimental and Other Scientific Purposes (1986), the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (1986), and Ukrainian Law no. 3447-IV On the Protection of Animals from Cruelty (2006). The investigations were sanctioned by the Commission on Bioethics of the Romodanov Neurosurgery Institute, National Academy of Medical Sciences of Ukraine (protocol no. 30 of April 11, 2019).

Additional information

Translated by N. Tarasyuk

About this article

Verify currency and authenticity via CrossMark

Cite this article

Medvediev, V.V., Oleksenko, N.P., Pichkur, L.D. et al. Effect of Implantation of a Fibrin Matrix Associated with Neonatal Brain Cells on the Course of an Experimental Spinal Cord Injury. Cytol. Genet. 56, 125–138 (2022). https://doi.org/10.3103/S0095452722020086

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.3103/S0095452722020086

  • Keywords: neurotransplantation
  • fibrin matrix
  • spinal cord injury
  • neonatal brain cells
  • locomotor function recovery
  • spasticity