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Peripheral nerve injury, stem cells, biopolymers, tissue engineering, experiment

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Petriv T. I., Tsymbalyuk Y. V., Potapov O. O., Kvasnitsʹkyy M. V., Honcharuk O. O., & Tatarchuk M. M. (2020). STEM CELL TECHNOLOGY IN PERIPHERAL NERVE RESTORATION. Eastern Ukrainian Medical Journal, 8(2), 210-229.;8(2):210-229


Peripheral nerve injuries are significant problem in the medical and socio-economic plan, as they are accompanied by a high incidence of disability by people of working age.

In recent decades, significant progress has been made in the restorative surgery of the peripheral nervous system, in particular through the introduction into clinical practice of microsurgical techniques. However, the problem of restoring the peripheral nerve after its traumatic injury has not been resolved yet.

Review article addresses the current state of developing stem cell technologies for peripheral nerve repair. Basic concepts of peripheral nerve regeneration after traumatic injury, methods of their restoration in experimental and clinic conditions are considered. The prospect of using stem cells of different origins is shown in the experiment by many authors, and the positive effect of stem cells on peripheral nerve regeneration is explained by their ability to secrete many trophic factors and differentiation to a neural phenotype. An essential issue in the tissue engineering approach is the choice of the optimal material to be used as a scaffold for large size peripheral nerve defects grafting.

The article focuses on the main types of stem cells, as well as their combinations with biopolymers, which have shown efficiency in the experiment. Despite the advances in the use of the latest technologies, the search for the necessary components is underway to provide the most favorable conditions for peripheral nerve regeneration in the clinic.;8(2):210-229
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1. Torres RY, Miranda GE. Epidemiology of Traumatic Peripheral Nerve Injuries Evaluated by Electrodiagnostic Studies in a Tertiary Care Hospital Clinic. P R Health Sci J. 2016;35(2):76-80. PMID: 27232868
2. Puzović V, Samardzić M, Jovanović M, Zivković B, Savić A, Rasulić L. Etiology and mechanisms of ulnar and median forearm nerve injuries. Vojnosanitetski Pregled. 2015;72(11):961-7. PMID: 26731969
3. Tsymbaliuk VI, Strafun SS, Haiko OG, Gaiovych VV. [The concept of limb function recovery in traumatic injury of peripheral nerves]. Ukrainian neurosurgical journal. 2016;(3):48-54.
4. Tsymbaliuk VI, Mogila VV, Nicholas ZhI. [Principles of surgical treatment of traumatic lesions of the median nerve at different levels]. Ukr Med Chasopis. 2005;47(3):64-8.
5. Rasulić L, Puzović V, Rotim K, Jovanović M, Samardžić M, Živković B, et al. The epidemiology of forearm nerve injuries – a retrospective study. Acta Clinica Croatica. 2015;54(1):19-24. PMID: 26058238
6. Jonsson S, Wiberg R, McGrath AM, Novikov LN, Wiberg M, Novikova LN, et al. Effect of Delayed Peripheral Nerve Repair on Nerve Regeneration, Schwann Cell Function and Target Muscle Recovery. PLoS ONE. 2013;8(2): e56484. doi: 10.1371/journal.pone.0056484.
7. Belanger K, Dinis TM, Taourirt S, Vidal G, Kaplan DL, Egles C. Recent Strategies in Tissue Engineering for Guided Peripheral Nerve Regeneration. Macromol Biosci. 2016;16(4):472-81. doi: 10.1002/mabi.201500367
8. Fairbairn NG, Meppelink AM, Ng-Glazier J, Randolph MA, Winograd JM. Augmenting peripheral nerve regeneration using stem cells: A review of current opinion. World J Stem Cells. 2015;7(1):11-26. doi: 10.4252/wjsc.v7.i1.11
9. Griffin JW, Hogan MV, Chhabra AB, Deal DN. Peripheral nerve repair and reconstruction. J Bone Joint Surg Am. 2013;95(23):2144-51. doi: 10.2106/JBJS.L.00704
10. Hansen C, Dinis TM, Vidal G, Ben-Mansour K, Bresson D, Egles C, et al. In-vivo analysis of nerve regeneration after sciatic nerve injury in a rat model. International Biomechanics. 2016;3(1):57-65. DOI: 10.1080/23335432.2016.1233077
11. Faroni A, Mobasseri SA, Kingham PJ, Reid AJ. Peripheral nerve regeneration: experimental strategies and future perspectives. Adv Drug Deliv Rev. 2015;82-83:160-7. doi: 10.1016/j.addr.2014.11.010
12. Tsymbaliuk VI, Tretyak IB, Gatsky OO. [The research of sciatic nerve combined plastics efficiency at it’s large defect by it’s functional recovery quantification in rats in experiment]. Ukrainian neurosurgical journal. 2012;(3):48-51.
13. Tsymbalyuk VI, Tretyak IB, Gatsky OO, Vernygorodskyj SV. [Morphometric evaluation of efficacy of modified nerve guidance tubes at bridging large rat sciatic nerve gap: experimental study]. Ukrainian neurosurgical journal. 2013;(1):32-9.
14. Sebben AD, Lichtenfels M, Braga da Silva JL. Peripheral nerve regeneration: cell therapy and neurotrophic factors. Rev Bras Ortop. 2011;46(6):643-9. doi: 10.1016/S2255-4971(15)30319-0
15. Seidel MF, Wise BL, Lane NE. Nerve growth factor: an update on the science and therapy. Osteoarthritis Cartilage. 2013;21(9):1223-8. doi: 10.1016/j.joca.2013.06.004
16. Gómez-Palacio-Schjetnan A, Escobar ML. Neurotrophins and synaptic plasticity. Neurogenesis and neural plasticity. In: Belzung C, Wigmore P, eds. Neurogenesis and Neural Plasticity. Springer; 2013. Current Topics in Behavioral Neurosciences. Vol.15. p.117-136. doi: 10.1007/7854_2012_231
17. Funa K, Sasahara M. The roles of PDGF in development and during neurogenesis in the normal and diseased nervous system. J Neuroimmune Pharmacol. 2014;9(2):168-81. doi: 10.1007/s11481-013-9479-z
18. Ramburrun P, Kumar P, Choonara YE, Bijukumar D, du Toit LC, Pillay V. A review of bioactive release from nerve conduits as a neurotherapeutic strategy for neuronal growth in peripheral nerve injury. BioMed Research International. Vol.2014, Article ID 132350, 19 pages, 2014. doi: 10.1155/2014/132350.
19. Godinho MJ, Teh L, Pollett MA, Goodman D, Hodgetts SI, Sweetman I, et al. Immunohistochemical, ultrastructural and functional analysis of axonal regeneration through peripheral nerve grafts containing Schwann cells expressing BDNF, CNTF or NT3. PLoS One. 2013;8(8):e69987. doi: 10.1371/journal.pone.0069987
20. Zhang Y, Zhang H, Katiella K, Huang W. Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair. Neural Regen Res. 2014;9(14):1358-64. doi: 10.4103/1673-5374.137588. PubMed PMID: 25221592; PubMed Central PMCID: PMC4160866
21. Liu G-Y, Jin Y, Zhang Q, Li R. Peripheral nerve repair: a hot spot analysis on treatment methods from 2010 to 2014. Neural Regen Res. 2015;10(6):996-1002. doi: 10.4103/1673-5374.158368. PMID: 26199620; PMCID: PMC4498365
22. Whitlock EL, Tuffaha SH, Luciano JP, Yan Y, Hunter DA, Magill CK, et al. Processed allografts and type I collagen conduits for repair of peripheral nerve gaps. Muscle Nerve. 2009;39(6):787-99. doi: 10.1002/mus.21220. PubMed PMID: 19291791
23. Paczkowska E, Kaczyńska K, Pius-Sadowska E, Rogińska D, Kawa M, Ustianowski P, Safranow K, et al. Humoral activity of cord blood-derived stem/progenitor cells: implications for stem cell-based adjuvant therapy of neurodegenerative disorders. PLoS One. 2013;8(12):e83833. doi: 10.1371/journal.pone.0083833. eCollection 2013. PubMed PMID: 24391835; PubMed Central PMCID: PMC3877125
24. Battiston B, Titolo P, Ciclamini D, Panero B. Peripheral Nerve Defects: Overviews of Practice in Europe. Hand Clin. 2017;33(3):545-550. doi: 10.1016/j.hcl.2017.04.005. Review. PubMed PMID: 28673630
25. Belkas JS, Shoichet MS, Midha R. Peripheral nerve regeneration through guidance tubes. Neurol Res. 2004;26(2):151-60. Review. doi: 10.1179/016164104225013798. PubMed PMID: 15072634
26. Brooks DN, Weber RV, Chao JD, Rinker BD, Zoldos J, Robichaux MR, et al. Processed nerve allografts for peripheral nerve reconstruction: a multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions. Microsurgery. 2012;32(1):1-14. doi: 10.1002/micr.20975. PubMed PMID: 22121093
27. Kim BS, Yoo JJ, Atala A. Peripheral nerve regeneration using acellular nerve grafts. J Biomed Mater Res A. 2004;68(2):201-9. doi: 10.1002/jbm.a.10045. PubMed PMID: 14704961
28. Ikegami Y, Ijima H. Development of heparin-conjugated nanofibers and a novel biological signal by immobilized growth factors for peripheral nerve regeneration. Journal of Bioscience and Bioengineering, 2020;129(3):354-362
29. Pabari A, Yang SY, Seifalian AM, Mosahebi A. Modern surgical management of peripheral nerve gap. J Plast Reconstr Aesthet Surg. 2010;63(12):1941-8. doi: 10.1016/j.bjps.2009.12.010. PMID: 20061198
30. Birch R. Nerve Repair. In: Wolfe S, Pederson W, Kozin SH. Green’s Operative Hand Surgery. 6th ed. Philadelphia; 2011p.1035-1074.
31. Zolotov AS, Pak OY. [K voprosu ob istoryi xirurgycheskix operacyj pry raneniyax peryferycheskych nervov]. Travmatologiya i ortopediya Rossii. 2013;(3):162-166.
32. Gatsky OO. [Kombinovana plastyka peryferychnych nerviv pry jich velykyx defektax (eksperymentalne doslidzhennya) [dysertaciya]. Kyiv: In-t nejrochirurgiyi im. A.P. Romodanova NAMN Ukraine; 2015. p23.
33. Kehoe S, Zhang XF, Boyd D. FDA approved guidance conduits and wraps for peripheral nerve injury: a review of materials and efficacy. Injury. 2012;43(5):553-72. doi: 10.1016/j.injury.2010.12.030
34. Safa B, Buncke G. Autograft Substitutes: Conduits and Processed Nerve Allografts. Hand Clin. 2016;32(2):127-40. doi: 10.1016/j.hcl.2015.12.012. Review. PubMed PMID: 27094886
35. Yan Y, MacEwan MR, Hunter DA, Farber S, Newton P, Tung TH, et al. Nerve regeneration in rat limb allografts: evaluation of acute rejection rescue. Plast Reconstr Surg. 2013;131(4):499e-511e. doi: 10.1097/PRS.0b013e31828275b7. PubMed PMID: 23542267; PubMed Central PMCID: PMC3613760
36. García-Medrano B, Mesuro Domínguez N, Simon Perez C, Garrosa García M, Gayoso del Villar S, Mayo Íscar A, et al. Repair of nerve injury by implanting prostheses obtained from isogenic acellular nerve segments. Revista Española de Cirugía Ortopédica y Traumatología (English Edition). 2017;61(5):359-366. doi: 10.1016/j.recote.2017.08.011
37. Neubauer D, Graham JB, Muir D. Chondroitinase treatment increases the effective length of acellular nerve grafts. Exp Neurol. 2007;207(1):163-70. doi:10.1016/j.expneurol.2007.06.006. PMID: 17669401; PMCID: PMC2956445
38. Gunn S, Cosetti M, Roland JT Jr. Processed allograft: novel use in facial nerve repair after resection of a rare racial nerve paraganglioma. Laryngoscope. 2010;120(4):S206. doi: 10.1002/lary.21674. PubMed PMID: 21225804
39. Karabekmez FE, Duymaz A, Moran SL. Early clinical outcomes with the use of decellularized nerve allograft for repair of sensory defects within the hand. Hand (NY). 2009 Sep;4(3):245-9. doi: 10.1007/s11552-009-9195-6. PubMed PMID: 19412640; PubMed Central PMCID: PMC2724628
40. Braga Silva J, Marchese GM, Cauduro CG, Debiasi M. Nerve conduits for treating peripheral nerve injuries: A systematic literature review. Hand Surg Rehabil. 2017;36(2):71-85. doi: 10.1016/j.hansur.2016.10.212. PubMed PMID: 28325431
41. Mackinnon SE, Dellon AL. Clinical nerve reconstruction with a bioabsorbable polyglycolic acid tube. Plast Reconstr Surg. 1990;85(3): 419-24. PMID:2154831. doi: 10.1097/00006534-199003000-00015
42. Costa MP, Teixeira NH, Longo MV, Gemperli R, Costa HJ. Combined polyglycolic acid tube and autografting versus autografting or polyglycolic acid tube alone. A comparative study of peripheral nerve regeneration in rats. Acta Cirurgica Brasileira. 2015;30(1):46-53. doi: 10.1590/S0102-86502015001000006. PubMed PMID:25627270
43. Konofaos P, Ver Halen JP. Nerve repair by means of tubulization: past, present, future. J Reconstr Microsurg. 2013;29(3):149-64. doi: 10.1055/s-0032-1333316. PMID: 23303520
44. Krarup C, Archibald SJ, Madison RD. Factors that influence peripheral nerve regeneration: an electrophysiological study of the monkey median nerve. Ann Neurol. 2002;51(1):69-81. PubMed PMID:11782986
45. Rodríguez FJ, Verdú E, Ceballos D, Navarro X. Nerve guides seeded with autologous schwann cells improve nerve regeneration. Exp Neurol. 2000;161(2):571-84. PubMed PMID: 10686077. DOI: 10.1006/exnr.1999.7315
46. Benga A, Zor F, Korkmaz A, Marinescu B, Gorantla V. The neurochemistry of peripheral nerve regeneration. Indian J Plast Surg. 2017;50(1):5-15. doi: 10.4103/ijps.IJPS_14_17. PubMed PMID: 28615804; PubMed Central PMCID: PMC5469235
47. Rbia N, Shin AY. The Role of Nerve Graft Substitutes in Motor and Mixed Motor/Sensory Peripheral Nerve Injuries. J Hand Surg Am. 2017;42(5):367-377. doi: 10.1016/j.jhsa.2017.02.017. PMID: 28473159
48. Lui H, Vaquette C, Bindra R. Tissue Engineering in Hand Surgery: A Technology Update. J Hand Surg Am. 2017;42(9):727-735. doi: 10.1016/j.jhsa.2017.06.014. PMID: 28751113
49. Sensharma P, Madhumathi G, Jayant RD, Jaiswal AK. Biomaterials and cells for neural tissue engineering: Current choices. Mater Sci Eng C Mater Biol Appl. 2017;77:1302-15. doi: 10.1016/j.msec.2017.03.264. PMID: 28532008
50. Wang EW, Zhang J, Huang JH. Repairing peripheral nerve injury using tissue engineering techniques. Neural Regen Res. 2015;10(9):1393-4. doi: 10.4103/1673-5374.165501. PMID: 26604891; PMCID: PMC4625496
51. Gao Y, Wang YL, Kong D, Qu B, Su XJ, Li H, et al. Nerve autografts and tissue-engineered materials for the repair of peripheral nerve injuries: a 5-year bibliometric analysis. Neural Regen Res. 2015;10(6):1003-8. doi: 10.4103/1673-5374.158369. PMID: 26199621; PMCID: PMC4498331.
52. Jones S, Eisenberg HM, Jia X. Advances and Future Applications of Augmented Peripheral Nerve Regeneration. Int J Mol Sci. 2016;17(9). pii: E1494. doi: 10.3390/ijms17091494. Review. PubMed PMID: 27618010; PubMed Central PMCID: PMC5037771
53. Jiang L, Jones S, Jia X. Stem Cell Transplantation for Peripheral Nerve Regeneration: Current Options and Opportunities. Int J Mol Sci. 2017;18(1):94. doi: 10.3390/ijms18010094. PMID: 28067783; PMCID: PMC5297728
54. Sullivan R, Dailey T, Duncan K, Abel N, Borlongan CV. Peripheral Nerve Injury: Stem Cell Therapy and Peripheral Nerve Transfer. Int J Mol Sci. 2016;17(12):2101. doi: 10.3390/ijms17122101. PMID: 27983642; PMCID: PMC5187901
55. Walsh S, Midha R. Practical considerations concerning the use of stem cells for peripheral nerve repair. Neurosurg Focus. 2009;26(2):E2. doi: 10.3171/FOC.2009.26.2.E2. PMID: 19435443
56. Culme-Seymour EJ, Davies JL, Hitchcock J, Mason J, Carpenter MK, Mason C. Cell Therapy Regulatory Toolkit: an online regulatory resource. Regen Med. 2015;10(5):531-4. doi: 10.2217/rme.15.33. PMID: 26237697
57. Grochmal J1, Midha R. Recent advances in stem cell-mediated peripheral nerve repair. Cells Tissues Organs. 2015;200(1):13-22. doi: 10.1159/000369450. PMID: 25825283
58. Hundepool CA, Nijhuis TH, Mohseny B, Selles RW, Hovius SE. The effect of stem cells in bridging peripheral nerve defects: a meta-analysis. J Neurosurg. 2014;121(1):195-209. doi: 10.3171/2014.4.JNS131260. PubMed PMID: 24816327
59. Nijhuis TH, Bodar CW, van Neck JW, Walbeehm ET, Siemionow M, Madajka M, et al. Natural conduits for bridging a 15-mm nerve defect: comparison of the vein supported by muscle and bone marrow stromal cells with a nerve autograft. J Plast Reconstr Aesthet Surg. 2013;66(2):251-9. doi: 10.1016/j.bjps.2012.09.011. PubMed PMID: 23063384.
60. Sverdlov ED, Mineev K. Mutation rate in stem cells: an underestimated barrier on the way to therapy. Trends Mol Med. 2013;19(5):273-80. doi: 10.1016/j.molmed.2013.01.004. Review. PubMed PMID: 23481596
61. Wang Y, Zhang Z, Chi Y, Zhang Q, Xu F, Yang Z, et al. Long-term cultured mesenchymal stem cells frequently develop genomic mutations but do not undergo malignant transformation. Cell Death & Disease. 2013;4(12):e950. doi: 10.1038/cddis.2013.480.
62. Dąbrowska AM, Skopiński P. Stem cells in regenerative medicine – from laboratory to clinical application – the eye. Cent Eur J Immunol. 2017;42(2):173-180. doi: 10.5114/ceji.2017.69360. PMID: 28860936. PMCID: PMC5573891.
63. Hakki SS, Turaç G, Bozkurt SB, Kayis SA, Hakki EE, Şahin E, et al. Comparison of Different Sources of Mesenchymal Stem Cells: Palatal versus Lipoaspirated Adipose Tissue. Cells Tissues Organs. 2017;204(5-6):228-240. doi: 10.1159/000478998
64. Heo JS, Choi Y, Kim HS, Kim HO. Comparison of molecular profiles of human mesenchymal stem cells derived from bone marrow, umbilical cord blood, placenta and adipose tissue. Int J Mol Med. 2016;37(1):115-25. doi: 10.3892/ijmm.2015.2413. PMID: 26719857 PMCID: PMC4687432
65. Macrin D, Joseph JP, Pillai AA, Devi A. Eminent Sources of Adult Mesenchymal Stem Cells and Their Therapeutic Imminence. Stem Cell Rev. 2017;13(6):741-756. doi: 10.1007/s12015-017-9759-8. PMID: 28812219
66. Lynch K, Pei M. Age associated communication between cells and matrix: a potential impact on stem cell-based tissue regeneration strategies. Organogenesis. 2014;10(3):289-98. doi: 10.4161/15476278.2014.970089. Review. PubMed PMID: 25482504; PubMed Central PMCID: PMC4594597
67. Chen J, Zhang D, Li Q, Yang D, Fan Z, Ma D, et al. Effect of different cell sheet ECM microenvironment on the formation of vascular network. Tissue Cell. 2016;48(5):442-51. doi: 10.1016/j.tice.2016.08.002. PubMed PMID: 27561623
68. Lopatina T, Kalinina N, Karagyaur M, Stambolsky D, Rubina K, Revischin A, et al. Adipose-derived stem cells stimulate regeneration of peripheral nerves: BDNF secreted by these cells promotes nerve healing and axon growth de novo. PLoS One. 2011;6(3):e17899. doi: 10.1371/journal.pone.0017899. PubMed PMID: 21423756; PubMed Central PMCID: PMC3056777
69. Liu G, Cheng Y, Guo S, Feng Y, Li Q, Jia H, et al. Transplantation of adipose-derived stem cells for peripheral nerve repair. Int J Mol Med. 2011;28(4):565-72. doi: 10.3892/ijmm.2011.725. PubMed PMID: 21687931
70. Jia H, Wang Y, Tong XJ, Liu GB, Li Q, Zhang LX, et al. Sciatic nerve repair by acellular nerve xenografts implanted with BMSCs in rats xenograft combined with BMSCs. Synapse. 2012;66(3):256-69. doi: 10.1002/syn.21508. PubMed PMID: 22127791
71. Mohammadi R, Azizi S, Delirezh N, Hobbenaghi R, Amini K, Malekkhetabi P. The use of undifferentiated bone marrow stromal cells for sciatic nerve regeneration in rats. Int J Oral Maxillofac Surg. 2012;41(5): 650-6. doi: 10.1016/j.ijom.2011.10.028. PMID: 22154576
72. Nijhuis TH, Bodar CW, van Neck JW, Walbeehm ET, Siemionow M, Madajka M, et al. Natural conduits for bridging a 15-mm nerve defect: comparison of the vein supported by muscle and bone marrow stromal cells with a nerve autograft. J Plast Reconstr Aesthet Surg. 2013;66(2):251-9. doi: 10.1016/j.bjps.2012.09.011. PubMed PMID: 23063384
73. Nijhuis TH, Brzezicki G, Klimczak A, Siemionow M. Isogenic venous graft supported with bone marrow stromal cells as a natural conduit for bridging a 20 mm nerve gap. Microsurgery. 2010;30(8): 639-45.doi: 10.1002/micr.20818. PMID: 20842703
74. Salomone R, Bento RF, Costa HJ, Azzi-Nogueira D, Ovando PC, Da-Silva CF, et al. Bone marrow stem cells in facial nerve regeneration from isolated stumps. Muscle and Nerve. 2013;48(3):423-9. doi: 10.1002/mus.23768. PMID: 23824709
75. Kingham PJ, Kolar MK, Novikova LN, Novikov LN, Wiberg M. Stimulating the neurotrophic and angiogenic properties of human adipose-derived stem cells enhances nerve repair. Stem Cells Dev. 2014;23(7):741-54. doi: 10.1089/scd.2013.0396. PMID: 24124760
76. Lin L, Du L. The role of secreted factors in stem cells-mediated immune regulation. Cell Immunol. 2018;326: 24-32. doi: 10.1016/j.cellimm.2017.07.010. PMID: 28778535
77. Vizoso FJ, Eiro N, Cid S, Schneider J, Perez-Fernandez R. Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine. Int J Mol Sci. 2017;18(9): pii: E1852. doi: 10.3390/ijms18091852. PMID: 28841158.; PMCID: PMC5618501
78. Petrova ES. [The use of stem cells to stimulate regeneration of damaged nerve]. Cytology. 2012; 54(7):525-540.
79. Kerman BE, Kim HJ, Padmanabhan K, Mei A, Georges S, Joens MS, et al. In vitro myelin formation using embryonic stem cells. Development. 2015;142(12):2213-25. doi: 10.1242/dev.116517. PMID: 26015546
80. Petrova ES, Isaeva EN, Korzhevskii DE. Differentiation of dissociated rat embryonic brain after allotransplantation into damaged nerve. Bull Exp Biol Med. 2013 Nov;156(1):136-8. PMID: 24319710. doi: 10.1007/s10517-013-2296-9
81. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145-7. PMID: 9804556. doi: 10.1126/science.282.5391.1145
82. Barberi T, Willis LM, Socci ND, Studer L. Derivation of multipotent mesenchymal precursors from human embryonic stem cells. PLoS Med. 2005;2(6):e161. DOI: 10.1371/journal.pmed.0020161. PMCID: PMC1160574; PMID: 15971941
83. Li Y, Wang R, Qiao N, Peng G, Zhang K, Tang K, et al. Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells. J Biol Chem. 2017;292(48):19590-19604. doi: 10.1074/jbc.M117.796383. PMID: 28972157.
84. Alić I, Kosi N, Kapuralin K, Gorup D, Gajović S, Pochet R, et al. Neural stem cells from mouse strain Thy1 YFP-16 are a valuable tool to monitor and evaluate neuronal differentiation and morphology. Neurosci Letter. 2016;634:32-41. doi: 10.1016/j.neulet.2016.10.001
85. Johnson TS, O'Neill AC, Motarjem PM, Nazzal J, Randolph M, Winograd JM. Tumor formation following murine neural precursor cell transplantation in a rat peripheral nerve injury model. J Reconstr Microsurg. 2008;24(8): 545-50. doi: 10.1055/s-0028-1088228. PMID: 18819061
86. Roche P, Alekseeva T, Widaa A, Ryan A, Matsiko A, Walsh M, et al. Olfactory Derived Stem Cells Delivered in a Biphasic Conduit Promote Peripheral Nerve Repair In Vivo. Stem Cells Transl Med. 2017;6(10): 1894-1904. doi: 10.1002/sctm.16-0420. PMID: 28960910
87. Batioglu-Karaaltin A, Karaaltin MV, Oztel ON, Ovali E, Sener BM, Adatepe T, et al. Human olfactory stem cells for injured facial nerve reconstruction in a rat model. Head Neck. 2016;38 (Suppl 1):E2011-20. doi: 10.1002/hed.24371. PubMed PMID: 26829770
88. Kabiri M, Oraee-Yazdani S, Shafiee A, Hanaee-Ahvaz H, Dodel M, Vaseei M, et al. Neuroregenerative effects of olfactory ensheathing cells transplanted in a multi-layered conductive nanofibrous conduit in peripheral nerve repair in rats. J Biomed Sci. 2015;22:35. doi: 10.1186/s12929-015-0144-0. PMID: 25986461; PMCID: PMC4437686.
89. Guérout N, Duclos C, Drouot L, Abramovici O, Bon-Mardion N, Lacoume Y, et al. Transplantation of olfactory ensheathing cells promotes axonal regeneration and functional racovery of peripheral nerve lesion in rats. Muscle Nerve. 2011;43(4):543-51. doi: 10.1002/mus.21907. PMID: 21305567
90. Guo J, Guo S, Wang Y, Yu Y. Promoting potential of adipose derived stem cells on peripheral nerve regeneration. Mol Med Rep. 2017;16(5):7297-304. doi: 10.3892/mmr.2017.7570. PMID:28944869. PMCID:PMC5865858
91. Ullah I, Park JM, Kang YH, Byun JH, Kim DG, Kim JH, et al. Transplantation of Human Dental Pulp-Derived Stem Cells or Differentiated Neuronal Cells from Human Dental Pulp-Derived Stem Cells Identically Enhances Regeneration of the Injured Peripheral Nerve. Stem Cells Dev. 2017;26(17):1247-57. doi: 10.1089/scd.2017.0068. PMID: 28657463.
92. Sanen K, Martens W, Georgiou M, Ameloot M, Lambrichts I, Phillips J, et al. Engineered neural tissue with Schwann cell differentiated human dental pulp stem cells: potential for peripheral nerve repair? J Tissue Eng Regen Med. 2017;11(12):3362-3372. doi: 10.1002/term.2249. PMID: 28052540.
93. Hei WH, Almansoori AA, Sung MA, Ju KW, Seo N, Lee SH, et al. Adenovirus vector-mediated ex vivo gene transfer of brain-derived neurotrophic factor (BDNF) tohuman umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) promotescrush-injured rat sciatic nerve regeneration. Neurosci Letters. 2017;643:111-120. doi: 10.1016/j.neulet.2017.02.030. PMID:28215880.
94. Xiao B, Rao F, Guo ZY, Sun X, Wang YG, Liu SY, et al. Extracellular matrix from human umbilical cord-derived mesenchymal stem cells as a scaffold for peripheral nerve regeneration. Neural Regen Res. 2016;11(7):1172-9. doi: 10.4103/1673-5374.187061. PMCID: PMC4994464; PMID: 27630705.
95. Guo ZY, Sun X, Xu XL, Zhao Q, Peng J, Wang Y. Human umbilical cord mesenchymal stem cells promote peripheral nerve repair via paracrine mechanisms. Neural Regen Res. 2015;10(4):651-8. doi: 10.4103/1673-5374.155442. PMID: 26170829; PMCID: PMC4424761
96. Cai S, Tsui YP, Tam KW, Shea GK, Chang RS, Ao Q, et al. Directed Differentiation of Human Bone Marrow Stromal Cells to Fate-Committed Schwann Cells. Stem Cell Reports. 2017;9(4):1097-1108. doi: 10.1016/j.stemcr.2017.08.004. PubMed PMID: 28890164; PubMed Central PMCID: PMC5639182.
97. Nijhuis TH, Brzezicki G, Klimczak A, Siemionow M. Isogenic venous graft supported with bone marrow stromal cells as a natural conduit for bridging a 20 mm nerve gap. Microsurgery. 2010;30(8):639-45. doi: 10.1002/micr.20818. PMID: 20842703
98. Wang Y, Jia H, Li WY, Tong XJ, Liu GB, Kang SW. Synergistic effects of bone mesenchymal stem cells and chondroitinase ABC on nerve regeneration after acellular nerve allograft in rats. Cell Mol Neurobiol. 2012;32(3):361-71. doi: 10.1007/s10571-011-9764-4. PMID: 22095068
99. Ladak A, Olson J, Tredget EE, Gordon T. Differentiation of mesenchymal stem cells to support peripheral nerve regeneration in a rat model. Exp Neurol. 2011;228(2):242-52. doi: 10.1016/j.expneurol.2011.01.013. PMID: 21281630
100. Zarbakhsh S, Bakhtiyari M, Faghihi A, Joghataei MT, Mehdizadeh M, Khoei S, et al. The effects of schwann and bone marrow stromal stem cells on sciatic nerve injury in rat: a comparison of functional recovery. Cell J. 2012;14(1):39-46. PubMed PMID:23626936; PubMed Central PMCID: PMC3635819
101. Yang Y, Yuan X, Ding F, Yao D, Gu Y, Liu J, et al. Repair of rat sciatic nerve gap by a silk fibroin-based scaffold added with bone marrow mesenchymal stem cells. Tissue Eng Part A. 2011;17(17-18):2231-44. doi: 10.1089/ten.TEA.2010.0633. PMID: 21542668
102. Zheng L, Cui HF. Enhancement of nerve regeneration along a chitosan conduit combined with bone marrow mesenchymal stem cells. J Mater Sci Mater Med. 2012;23(9):2291-302. doi: 10.1007/s10856-012-4694-3. PMID: 22661248
103. de Luca AC, Fonta CM, Raffoul W, di Summa PG, Lacour SP. In vitro evaluation of gel-encapsulated adipose derived stem cells: Biochemical cues for in vivo peripheral nerve repair. J Tissue Eng Regen Med. 2018;12(3):676-686. doi: 10.1002/term.2486
104. Xie S, Lu F, Han J, Tao K, Wang H, Simental A, et al. Efficient generation of functional Schwann cells from adipose-derived stem cells in defined conditions. Cell Cycle. 2017;16(9):841-851. doi: 10.1080/15384101.2017.1304328. PubMed PMID: 28296571; PubMed Central PMCID: PMC5444349
105. Semenova VM, Lysyanyj NY, Stajno LP, Belskaya LN, Egorova DM. [Proliferative and differentiated potential of mesenchymal stem cells from adipose tissue under cultivation conditions]. Ukrainian neurosurgical journal. 2014;3:24-9.
106. Abbas OL, Borman H, Uysal ÇA, Gönen ZB, Aydin L, Helvacioğlu F, et al. Adipose-Derived Stem Cells Enhance Axonal Regeneration through Cross-Facial Nerve Grafting in a Rat Model of Facial Paralysis. Plast Reconstr Surg. 2016;138(2):387-96. doi: 10.1097/PRS.0000000000002351. PubMed PMID: 27465163
107. Klein SM, Vykoukal J, Li DP, Pan HL, Zeitler K, Alt E, et al. Peripheral Motor and Sensory Nerve Conduction following Transplantation of Undifferentiated Autologous Adipose Tissue-Derived Stem Cells in a Biodegradable U.S. Food and Drug Administration-Approved Nerve Conduit. Plast Reconstr Surg. 2016;138(1):132-9. doi: 10.1097/PRS.0000000000002291. PubMed PMID: 27348645
108. Sowa Y1, Imura T, Numajiri T, Nishino K, Fushiki S. Adipose-derived stem cells produce factors enhancing peripheral nerve regeneration: influence of age and anatomic site of origin. Stem Cells Dev. 2012;21(11):1852-62. doi: 10.1089/scd.2011.0403. PMID: 22150084
109. Tomita K, Madura T, Mantovani C, Terenghi G. Differentiated adipose-derived stem cells promote myelination and enhance functional recovery in a rat model of chronic denervation. J Neurosci Res. 2012;90(7): 1392-402. doi: 10.1002/jnr.23002. PMID: 22419645
110. Erba P, Mantovani C, Kalbermatten DF, Pierer G, Terenghi G, Kingham PJ. Regeneration potential and survival of transplanted undifferentiated adipose tissue-derived stem cells in peripheral nerve conduits. J Plast Reconstr Aesthet Surg. 2010;63(12):e811-7. doi: 10.1016/j.bjps.2010.08.013. PubMed PMID: 20851070
111. Sun F, Zhou K, Mi WJ, Qiu JH. Repair of facial nerve defects with decellularized artery allografts containing autologous adipose-derived stem cells in a rat model. Neuroscie Lett. 2011;499(2): 104-8. doi: 10.1016/j.neulet.2011.05.043. PMID: 21651959
112. Kappos EA, Engels PE, Tremp M, Meyer zu Schwabedissen M, di Summa P, Fischmann A, et al. Peripheral Nerve Repair: Multimodal Comparison of the Long-Term Regenerative Potential of Adipose Tissue-Derived Cells in a Biodegradable Conduit. Stem Cells Dev. 2015;24(18):2127-41. doi: 10.1089/scd.2014.0424. PubMed PMID: 26134465
113. di Summa PG, Kingham PJ, Campisi CC, Raffoul W, Kalbermatten DF. Collagen (NeuraGen®) nerve conduits and stem cells for peripheral nerve gap repair. Neurosci Lett. 2014;572:26-31. doi: 10.1016/j.neulet.2014.04.029. PMID: 24792394
114. di Summa PG, Kalbermatten DF, Raffoul W, Terenghi G, Kingham PJ. Extracellular matrix molecules enhance the neurotrophic effect of Schwann cell-like differentiated adipose-derived stem cells and increase cell survival under stress conditions. Tissue Eng Part A. 2013;19(3-4): 368-79. doi: 10.1089/ten.TEA.2012.0124. PMID: 22897220; PMCID: PMC3542878
115. Fairbairn NG, Randolph MA, Redmond RW. The clinical applications of human amnion in plastic surgery. J Plast Reconstr Aesthet Surg. 2014;67(5):662-75. doi: 10.1016/j.bjps.2014.01.031. PMID: 24560801
116. Gärtner A, Pereira T, Alves MG, Armada-da-Silva PA, Amorim I, Gomes R, et al. Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton’s jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: in vitro and in vivo analysis. Differentiation. 2012;84(5):355-65. doi: 10.1016/j.diff.2012.10.001. PMID: 23142731
117. Matsuse D, Kitada M, Kohama M, Nishikawa K, Makinoshima H, Wakao S, et al. Human umbilical cord-derived mesenchymal stromal cells differentiate into functional Schwann cells that sustain peripheral nerve regeneration. J Neuropathol Exp Neurol. 2010 Sep;69(9):973-85. doi: 10.1097/NEN.0b013e3181eff6dc. PubMed PMID: 20720501
118. Cottle BJ, Lewis FC, Shone V, Ellison-Hughes GM. Skeletal muscle-derived interstitial progenitor cells (PICs) display stem cell properties, being clonogenic, self-renewing, and multi-potent in vitro and in vivo. Stem Cell Res Ther. 2017;8(1): 158. doi: 10.1186/s13287-017-0612-4. PubMed PMID: 28676130; PubMed Central PMCID: PMC5496597
119. Tamaki T, Hirata M, Soeda S, Nakajima N, Saito K, Nakazato K, et al. Preferential and comprehensive reconstitution of severely damaged sciatic nerve using murine skeletal muscle-derived multipotent stem cells. PLoS One. 2014;9(3):e91257. doi: 10.1371/journal.pone.0091257. eCollection 2014. PubMed PMID: 24614849; PubMed Central PMCID: PMC3948784
120. Johnson TS, O'Neill AC, Motarjem PM, Amann C, Nguyen T, Randolph MA, et al. Photochemical tissue bonding: a promising technique for peripheral nerve repair. J Surg Res. 2007;143(2):224-9. PubMed PMID: 17543988. DOI: 10.1016/j.jss.2007.01.028
121. Yoshikawa M, Nakasa T, Ishikawa M, Adachi N, Ochi M. Evaluation of autologous skeletal muscle-derived factors for regenerative medicine applications. Bone Joint Res. 2017;6(5): 277-83. doi: 10.1302/2046-3758.65.BJR-2016-0187.R1. PMID: 28473335; PMCID:PMC5457645
122. Tamaki T, Hirata M, Nakajima N, Saito K, Hashimoto H, Soeda S, et al. A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery. PLoS One. 2016;11(11):e0166639. PubMed PMID: 27846318; PubMed Central PMCID: PMC5112878. doi: 10.1371/journal.pone.0166639
123. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4): 663-76. PMID: 16904174. DOI: 10.1016/j.cell.2006.07.024
124. Kang S, Chen X, Gong S, Yu P, Yau S, Su Z, et al. Characteristic analyses of a neural differentiation model from iPSC-derived neuron according to morphology, physiology, and global gene expression pattern. Sci Rep. 2017;7(1):12233. doi: 10.1038/s41598-017-12452-x. PubMed PMID: 28947763; PubMed Central PMCID: PMC5612987
125. Ikeda M, Uemura T, Takamatsu K, Okada M, Kazuki K, Tabata Y, et al. Acceleration of peripheral nerve regeneration using nerve conduits in combination with induced pluripotent stem cell technology and a basic fibroblast growth factor drug delivery system. J Biomed Mater Res A. 2014;102(5):1370-8. doi: 10.1002/jbm.a.34816. PubMed PMID: 23733515
126. Satarian L, Javan M, Kiani S, Hajikaram M, Mirnajafi-Zadeh J, Baharvand H. Engrafted human induced pluripotent stem cell-derived anterior specified neural progenitors protect the rat crushed optic nerve. PLoS One. 2013;8(8):e71855.doi:10.1371/journal.pone.0071855. PubMed PMID: 23977164; PubMed Central PMCID: PMC3747054
127. Uemura T, Takamatsu K, Ikeda M, Okada M, Kazuki K, Ikada Y, et al. Transplantation of induced pluripotent stem cell-derived neurospheres for peripheral nerve repair. Biochem Biophys Res Commun. 2012;419(1):130-5. doi: 10.1016/j.bbrc.2012.01.154. PMID: 22333572
128. Ben-David U, Benvenisty N. The tumorigenicity of human embryonic and induced pluripotent stem cells. Nat Rev Cancer. 2011;11(4): 268-77. doi: 10.1038/nrc3034
129. Sieber-Blum M, Grim M, Hu Y, Szeder V. Pluripotent neural crest stem cells in the adult hair follicle. Dev Dyn. 2004;231(2):258-69. doi: 10.1002/dvdy.20129. PMID: 15366003
130. Tsymbalyuk VI, Molotkovets VYu, Medvedyev VV, Luzan BM, Petriv TI. [Efficiency weld the damaged peripheral nerve rat according to estimates sciatic nerve functional index]. Ukrainian neurological journal. 2017;(2):63-68
131. Achilleos A, Trainor PA. Neural crest stem cells: discovery, properties and potential for therapy. Cell Res. 2012;22(2):288-304. doi: 10.1038/cr.2012.11. PMID: 22231630; PMCID: PMC3271580
132. Mii S, Duong J, Tome Y, Uchugonova A, Liu F, Amoh Y, et al. Nestin-Expressing Hair-Follicle-Associated Pluripotent (HAP) Stem Cells Promote Whisker Sensory-Nerve Growth in Long-Term 3D-Gelfoam® Histoculture. Methods Mol Biol. 2016;1453:39-47. doi: 10.1007/978-1-4939-3786-8_6. PubMed PMID: 27431245
133. Tsymbaliuk VY, Medvedev VV. [Neurogenic stem cells]. Kiev:Koval; 2005. P.596
134. Hoffman RM. Introduction to Hair-Follicle-Associated Pluripotent Stem Cells. Methods Mol Biol. 2016;1453:1-5. doi: 10.1007/978-1-4939-3786-8_1. PMID: 27431240
135. Hoffman RM. Nestin-expressing hair follicle-accessible pluripotent stem cells for nerve and spinal cord repair. Cells Tissues Organs. 2014 Jul; 200(1): 42-7. doi: 10.1159/000366098. PMID: 25766743
136. Vasyliev RG, Rodnichenko AE, Shamalo SN, Demidchouk AS, Labunets IF, Chaikovskii YuB, et al. Effects of Neural Crest-Derived Multipotent Stem Cells on Regeneration of an Injured Peripheral Nerve in Mice. Neurophysiology. 2015;47(1): 80-3. doi:10.1007/s11062-015-9501-6.
137. Vasyliev RG. [Multipotent Stem Cells of Bulbar Region of Hair Follicle with Properties of Neural Crest Derivatives]. Problems of cryobiology. 2012; 22 (2):165-68
138. Motohashi T, Yamanaka K, Chiba K, Aoki H, Kunisada T. Unexpected multipotency of melanoblasts isolated from murine skin. Stem Cells. 2009;27(4):888-97. doi: 10.1634/stemcells.2008-0678. PMID: 19350691
139. Amoh Y, Li L, Katsuoka K, Penman S, Hoffman RM. Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons. Proc Natl Acad Sci U S A. 2005;102(15):5530-4. PubMed PMID: 15802470; PubMed Central PMCID: PMC556262. DOI: 10.1073/pnas.0501263102
140. Najafzadeh N, Esmaeilzade B, Dastan Imcheh M. Hair follicle stem cells: In vitro and in vivo neural differentiation. World J Stem Cells. 2015;7(5):866-72. doi:10.4252/wjsc.v7.i5.866. PMID: 26131317; PMCID: PMC4478633
141. Amoh Y, Kanoh M, Niiyama S, Kawahara K, Sato Y, Katsuoka K, et al. Hoffman. Human and mouse hair follicles contain both multipotent and monopotent stem cells. Cell Cycle. 2009;8(1):176-7. doi: 10.4161/cc.8.1.7342. PMID: 19106614
142. Amoh Y, Hoffman RM. Hair follicle-associated-pluripotent (HAP) stem cells. Cell Cycle. 2017;16(22):2169-2175. PMID: 28749199. doi: 10.1080/15384101.2017.1356513
143. Amoh Y, Aki R, Hamada Y, Niiyama S, Eshima K, Kawahara K, et al. Nestin-positive hair follicle pluripotent stem cells can promote regeneration of impinged peripheral nerve injury. J Dermatol. 2012;39(1):33-8. doi: 10.1111/j.1346-8138.2011.01413.x. PMID: 22098554
144. Amoh Y, Kanoh M, Niiyama S, Hamada Y, Kawahara K, Sato Y, et al. Human hair follicle pluripotent stem (hfPS) cells promote regeneration of peripheral-nerve injury: an advantageous alternative to ES and iPS cells. J Cell Biochem. 2009;107(5): 1016-20. doi: 10.1002/jcb.22204. PMID: 19507228
145. Amoh Y, Li L, Campillo R, Kawahara K, Katsuoka K, Penman S, et al. Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves. Proc Natl Acad Sci USA. 2005;102(49):17734-8. doi: 10.1073/pnas.0508440102. PubMed PMID: 16314569; PubMed Central PMCID: PMC1308908
146. Lin H, Liu F, Zhang C, Zhang Z, Guo J, Ren C, et al. Pluripotent hair follicle neural crest stem-cell-derived neurons and schwann cells functionally repair sciatic nerves in rats. Mol Neurobiol. 2009;40(3):216-23. doi: 10.1007/s12035-009-8082-z. PMID: 19728182
147. Yamazaki A, Obara K, Tohgi N, Shirai K, Mii S, Hamada Y, et al. Implanted hair-follicle-associated pluripotent (HAP) stem cells encapsulated in polyvinylidene fluoride membrane cylinders promote effective recovery of peripheral nerve injury. Cell Cycle. 2017;16(20):1927-32. doi: 10.1080/15384101.2017.1363941. PMID: 28886268; PMCID: PMC5638363
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