The role of mesenchymal stem cells in peripheral nerve regeneration

Authors

DOI:

https://doi.org/10.14739/2310-1237.2024.2.297836

Keywords:

regeneration, mesenchymal stem cells, peripheral nerve

Abstract

Taking into account the imperfect results of treatment of peripheral nerve injuries and despite the large number of already performed clinical and experimental studies on the regeneration of peripheral nerves, the search for new effective methods of treatment of this pathology remains relevant until now. Cell therapy is one of the innovative and promising therapeutic approaches in the field of nerve regeneration. Mesenchymal stem cells (MSCs) were first introduced in 1966 by Friedenstein and colleagues. This is a class of multipotent stem cells of mesodermal origin, which have low immunogenicity, but high capacity for self-renewal and multidirectional differentiation potential. They were found in almost all tissues. According to the International Society for Cell Therapy (ISCT, Vancouver, Canada), human MSCs express CD73, CD105, CD90 and lack hematopoietic stem cell markers (CD34, CD14, CD45, CD11b, CD79a, and HLA-DR).

There is no consensus regarding the main mechanism of action of MSCs in stimulating nerve regeneration, but in general, most likely, they perform a trophic function, inhibit proapoptotic pathways and enhance the intrinsic regenerative capacity of the nerve. The ability of MSCs to produce various immunoregulatory factors is also known, which leads to the reduction of an inadequate inflammatory response after nerve damage. MSCs can transdifferentiate into Schwann cells, acquire a Schwann-like phenotype, or stimulate the activity of endogenous Schwann cells, which are one of the key regulators of reparative nerve regeneration. MSCs also take part in the remyelination of damaged nerves due to the synthesis and release of myelin proteins MBP or P0. MSCs create an enhanced neuroprotective microenvironment that prevents nerve degeneration, supports axon growth, neurogenesis, and cellular metabolism. The property of stem cells to produce neurotrophic factors is also well known. It is interesting to note that endogenous stem cells, including those circulating in peripheral blood, are much less studied. A detailed study of various pharmacological, gene-modifying, or biomodifying methods of endogenous stem cell mobilization, their properties, and identification may be promising in regenerative medicine in general and peripheral nerve regeneration in particular.

Author Biographies

N. M. Nevmerzhytska, Bogomolets National Medical University, Kyiv, Ukraine

MD, Assistant of the Department of Histology and Embryology

L. M. Yaremenko, Bogomolets National Medical University, Kyiv, Ukraine

MD, PhD, DSc, Professor of the Department of Histology and Embryology

O. M. Grabovyi, Bogomolets National Medical University, Kyiv, Ukraine

MD, PhD, DSc, Professor, Head of the Department of Histology and Embryology

References

Alvites RD, Branquinho MV, Sousa AC, Amorim I, Magalhães R, João F, et al. Combined Use of Chitosan and Olfactory Mucosa Mesenchymal Stem/Stromal Cells to Promote Peripheral Nerve Regeneration In Vivo. Stem Cells Int. 2021;2021:6613029. doi: https://doi.org/10.1155/2021/6613029

Grabovyi OM, Nevmerzhytska NM, Shepelev SE, Kondaurova HY. Dexamethasone and granulocyte colony-stimulating factor change the regenerative neuroma morphology. World of medicine and biology. 2023;0(4):187-92. doi: https://doi.org/10.26724/2079-8334-2023-4-86-187-192

Ye Z, Wei J, Zhan C, Hou J. Role of Transforming Growth Factor Beta in Peripheral Nerve Regeneration: Cellular and Molecular Mechanisms. Front Neurosci. 2022;16:917587. doi: https://doi.org/10.3389/fnins.2022.917587

Min Q, Parkinson DB, Dun XP. Migrating Schwann cells direct axon regeneration within the peripheral nerve bridge. Glia. 2021;69(2):235-54. doi: https://doi.org/10.1002/glia.23892

Carvalho CR, Reis RL, Oliveira JM. Fundamentals and Current Strategies for Peripheral Nerve Repair and Regeneration. Adv Exp Med Biol. 2020;1249:173-201. doi: https://doi.org/10.1007/978-981-15-3258-0_12

Molnár K, Nógrádi B, Kristóf R, Mészáros Á, Pajer K, Siklós L, et al. Motoneuronal inflammasome activation triggers excessive neuroinflammation and impedes regeneration after sciatic nerve injury. J Neuroinflammation. 2022;19(1):68. doi: https://doi.org/10.1186/s12974-022-02427-9

Kubiak CA, Grochmal J, Kung TA, Cederna PS, Midha R, Kemp SWP. Stem-cell-based therapies to enhance peripheral nerve regeneration. Muscle Nerve. 2020;61(4):449-459. doi: https://doi.org/10.1002/mus.26760

Lim EF, Hoghooghi V, Hagen KM, Kapoor K, Frederick A, Finlay TM, et al. Presence and activation of pro-inflammatory macrophages are associated with CRYAB expression in vitro and after peripheral nerve injury. J Neuroinflammation. 2021;18(1):82. doi: https://doi.org/10.1186/s12974-021-02108-z

Grabovyi OM, Nevmerzhytska NM, Alyokhin AB, Kostynskyi HB, Rytikova NV. [Modulation of the tissue composition of regenerative neuroma by dexamethasone and granulocyte colony-stimulating factor]. Pathologia. 2023;20(2):118-25. Ukrainian. 10.14739/2310-1237.2023.2.285124

Tang X, Li Q, Huang T, Zhang H, Chen X, Ling J, et al. Regenerative Role of T Cells in Nerve Repair and Functional Recovery. Front Immunol. 2022;13:923152. doi: https://doi.org/10.3389/fimmu.2022.923152

Mokarram N, Dymanus K, Srinivasan A, Lyon JG, Tipton J, Chu J, et al. Immunoengineering nerve repair. Proc Natl Acad Sci U S A. 2017;114(26):E5077-E5084. doi: https://doi.org/10.1073/pnas.1705757114

Ehmedah A, Nedeljkovic P, Dacic S, Repac J, Draskovic-Pavlovic B, Vučević D, et al. Effect of Vitamin B Complex Treatment on Macrophages to Schwann Cells Association during Neuroinflammation after Peripheral Nerve Injury. Molecules. 2020;25(22):5426. doi: https://doi.org/10.3390/molecules25225426

Wang AY, Loh CY, Shen HH, Hsieh SY, Wang IK, Lee CM, et al. Human Wharton’s Jelly Mesenchymal Stem Cell-Mediated Sciatic Nerve Recovery Is Associated with the Upregulation of Regulatory T Cells. Int J Mol Sci. 2020;21(17):6310. doi: https://doi.org/10.3390/ijms21176310

Stratton JA, Holmes A, Rosin NL, Sinha S, Vohra M, Burma NE, et al. Macrophages Regulate Schwann Cell Maturation after Nerve Injury. Cell Rep. 2018;24(10):2561-72.e6. doi: https://doi.org/10.1016/j.celrep.2018.08.004

Dong X, Liu S, Yang Y, Gao S, Li W, Cao J, et al. Aligned microfiber-induced macrophage polarization to guide schwann-cell-enabled peripheral nerve regeneration. Biomaterials. 2021;272:120767. doi: https://doi.org/10.1016/j.biomaterials.2021.120767

Yi S, Zhang Y, Gu X, Huang L, Zhang K, Qian T, et al. Application of stem cells in peripheral nerve regeneration. Burns Trauma. 2020;8:tkaa002. doi: https://doi.org/10.1093/burnst/tkaa002

Bunn SJ, Lai A, Li J. DC Electric Fields Induce Perpendicular Alignment and Enhanced Migration in Schwann Cell Cultures. Ann Biomed Eng. 2019;47(7):1584-95. doi: https://doi.org/10.1007/s10439-019-02259-4

Hartlehnert M, Derksen A, Hagenacker T, Kindermann D, Schäfers M, Pawlak M, et al. Schwann cells promote post-traumatic nerve inflammation and neuropathic pain through MHC class II. Sci Rep. 2017;7(1):12518. doi: https://doi.org/10.1038/s41598-017-12744-2

Lavorato A, Raimondo S, Boido M, Muratori L, Durante G, Cofano F, et al. Mesenchymal Stem Cell Treatment Perspectives in Peripheral Nerve Regeneration: Systematic Review. Int J Mol Sci. 2021;22(2):572. doi: https://doi.org/10.3390/ijms22020572

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: https://doi.org/10.3390/ijms18010094

Maqsood M, Kang M, Wu X, Chen J, Teng L, Qiu L. Adult mesenchymal stem cells and their exosomes: Sources, characteristics, and application in regenerative medicine. Life Sci. 2020;256:118002. doi: https://doi.org/10.1016/j.lfs.2020.118002

Zhang RC, Du WQ, Zhang JY, Yu SX, Lu FZ, Ding HM, et al. Mesenchymal stem cell treatment for peripheral nerve injury: a narrative review. Neural Regen Res. 2021;16(11):2170-6. doi: https://doi.org/10.4103/1673-5374.310941

Kizilay Z, Aktas S, Kahraman Cetin N, Bakay Ilhan D, Ersoy G, Erken HA. Effect of systemic application of bone marrow-derived mesenchymal stem cells on healing of peripheral nerve injury in an experimental sciatic nerve injury model. Turk Neurosurg. 2017 Jul 12. doi: https://doi.org/10.5137/1019-5149.JTN.20811-17.1

Ma Y, Dong L, Zhou D, Li L, Zhang W, Zhen Y, et al. Extracellular vesicles from human umbilical cord mesenchymal stem cells improve nerve regeneration after sciatic nerve transection in rats. J Cell Mol Med. 2019;23(4):2822-35. doi: https://doi.org/10.1111/jcmm.14190

Mitsuzawa S, Zhao C, Ikeguchi R, Aoyama T, Kamiya D, Ando M, et al. Pro-angiogenic scaffold-free Bio three-dimensional conduit developed from human induced pluripotent stem cell-derived mesenchymal stem cells promotes peripheral nerve regeneration. Sci Rep. 2020;10(1):12034. doi: https://doi.org/10.1038/s41598-020-68745-1

Nevmerzhytska NM, Yaremenko LM, Chuhray SM, Grabovyi OM. Treatment methods for peripheral nerve injuries (a literature review). Zaporozhye medical journal. 2023;25(4):365-9. doi: https://doi.org/10.14739/2310-1210.2023.4.273073

Bojanic C, To K, Zhang B, Mak C, Khan WS. Human umbilical cord derived mesenchymal stem cells in peripheral nerve regeneration. World J Stem Cells. 2020 Apr 26;12(4):288-302. doi: https://doi.org/10.4252/wjsc.v12.i4.288

Mao Q, Nguyen PD, Shanti RM, Shi S, Shakoori P, Zhang Q, et al. Gingiva-Derived Mesenchymal Stem Cell-Extracellular Vesicles Activate Schwann Cell Repair Phenotype and Promote Nerve Regeneration. Tissue Eng Part A. 2019;25(11-12):887-900. doi: https://doi.org/10.1089/ten.TEA.2018.0176

Wang YH, Guo YC, Wang DR, Liu JY, Pan J. Adipose Stem Cell-Based Clinical Strategy for Neural Regeneration: A Review of Current Opinion. Stem Cells Int. 2019;2019:8502370. doi: https://doi.org/10.1155/2019/8502370

Chen X, Wang S, Cao W. Mesenchymal stem cell-mediated immunomodulation in cell therapy of neurodegenerative diseases. Cell Immunol. 2018;326:8-14. doi: https://doi.org/10.1016/j.cellimm.2017.06.006

Mathot F, Shin AY, Van Wijnen AJ. Targeted stimulation of MSCs in peripheral nerve repair. Gene. 2019;710:17-23. doi: https://doi.org/10.1016/j.gene.2019.02.078

De la Rosa MB, Kozik EM, Sakaguchi DS. Adult Stem Cell-Based Strategies for Peripheral Nerve Regeneration. Adv Exp Med Biol. 2018;1119:41-71. doi: https://doi.org/10.1007/5584_2018_254

Bucan V, Vaslaitis D, Peck CT, Strauß S, Vogt PM, Radtke C. Effect of Exosomes from Rat Adipose-Derived Mesenchymal Stem Cells on Neurite Outgrowth and Sciatic Nerve Regeneration After Crush Injury. Mol Neurobiol. 2019;56(3):1812-24. doi: https://doi.org/10.1007/s12035-018-1172-z

Sharma AD, Wiederin J, Uz M, Ciborowski P, Mallapragada SK, Gendelman HE, et al. Proteomic analysis of mesenchymal to Schwann cell transdifferentiation. J Proteomics. 2017;165:93-101. doi: https://doi.org/10.1016/j.jprot.2017.06.011

Rao Z, Lin Z, Song P, Quan D, Bai Y. Biomaterial-Based Schwann Cell Transplantation and Schwann Cell-Derived Biomaterials for Nerve Regeneration. Front Cell Neurosci. 2022 Jun 28;16:926222. doi: https://doi.org/10.3389/fncel.2022.926222

Zhang R, Rosen JM. The role of undifferentiated adipose-derived stem cells in peripheral nerve repair. Neural Regen Res. 2018;13(5):757-63. doi: https://doi.org/10.4103/1673-5374.232457

Li N, Hua J. Interactions between mesenchymal stem cells and the immune system. Cell Mol Life Sci. 2017;74(13):2345-60. doi: https://doi.org/10.1007/s00018-017-2473-5

Li X, Guan Y, Li C, Zhang T, Meng F, Zhang J, et al. Immunomodulatory effects of mesenchymal stem cells in peripheral nerve injury. Stem Cell Res Ther. 2022;13(1):18. doi: https://doi.org/10.1186/s13287-021-02690-2

Togashi Y, Shitara K, Nishikawa H. Regulatory T cells in cancer immunosuppression – implications for anticancer therapy. Nat Rev Clin Oncol. 2019;16(6):356-71. doi: https://doi.org/10.1038/s41571-019-0175-7

Savage PA, Klawon DEJ, Miller CH. Regulatory T Cell Development. Annu Rev Immunol. 2020;38:421-53. doi: https://doi.org/10.1146/annurev-immunol-100219-020937

Hu X, Leak RK, Thomson AW, Yu F, Xia Y, Wechsler LR, et al. Promises and limitations of immune cell-based therapies in neurological disorders. Nat Rev Neurol. 2018;14(9):559-68. doi: https://doi.org/10.1038/s41582-018-0028-5

Jiang W, Xu J. Immune modulation by mesenchymal stem cells. Cell Prolif. 2020;53(1):e12712. doi: https://doi.org/10.1111/cpr.12712

Uz M, Das SR, Ding S, Sakaguchi DS, Claussen JC, Mallapragada SK. Advances in Controlling Differentiation of Adult Stem Cells for Peripheral Nerve Regeneration. Adv Healthc Mater. 2018;7(14):e1701046. doi: https://doi.org/10.1002/adhm.201701046

Cintron-Colon AF, Almeida-Alves G, VanGyseghem JM, Spitsbergen JM. GDNF to the rescue: GDNF delivery effects on motor neurons and nerves, and muscle re-innervation after peripheral nerve injuries. Neural Regen Res. 2022;17(4):748-53. doi: https://doi.org/10.4103/1673-5374.322446

El Ouaamari Y, Van den Bos J, Willekens B, Cools N, Wens I. Neurotrophic Factors as Regenerative Therapy for Neurodegenerative Diseases: Current Status, Challenges and Future Perspectives. Int J Mol Sci. 2023;24(4):3866. doi: https://doi.org/10.3390/ijms24043866

Braschi C, Capsoni S, Narducci R, Poli A, Sansevero G, Brandi R, et al. Intranasal delivery of BDNF rescues memory deficits in AD11 mice and reduces brain microgliosis. Aging Clin Exp Res. 2021;33(5):1223-38. doi: https://doi.org/10.1007/s40520-020-01646-5

Khazaei M, Ahuja CS, Nakashima H, Nagoshi N, Li L, Wang J, et al. GDNF rescues the fate of neural progenitor grafts by attenuating Notch signals in the injured spinal cord in rodents. Sci Transl Med. 2020;12(525):eaau3538. doi: https://doi.org/10.1126/scitranslmed.aau3538

Chao MV, Bothwell MA, Ross AH, Koprowski H, Lanahan AA, Buck CR, et al. Gene transfer and molecular cloning of the human NGF receptor. Science. 1986;232(4749):518-21. doi: https://doi.org/10.1126/science.3008331

Numakawa T, Odaka H. Roles of Trk receptors, tyrosine kinase receptors for neurotrophins, in the developing CNS. In: Receptor Tyrosine Kinases in Neurodegenerative and Psychiatric Disorders. Elsevier; 2023. p. 79-15. doi: https://doi.org/10.1016/B978-0-443-18677-6.00008-7

Wise BL, Seidel MF, Lane NE. The evolution of nerve growth factor inhibition in clinical medicine. Nat Rev Rheumatol. 2021;17(1):34-46. doi: https://doi.org/10.1038/s41584-020-00528-4

Cuello AC. Rita Levi-Montalcini, NGF Metabolism in Health and in the Alzheimer’s Pathology. Adv Exp Med Biol. 2021;1331:119-44. doi: https://doi.org/10.1007/978-3-030-74046-7_9

Sacchetti M, Bruscolini A, Lambiase A. Neurotrophic factors and nerve growth factor in ocular allergy. Curr Opin Allergy Clin Immunol. 2019;19(5):510-6. doi: https://doi.org/10.1097/ACI.0000000000000555

Liao CF, Chen CC, Lu YW, Yao CH, Lin JH, Way TD, et al. Effects of endogenous inflammation signals elicited by nerve growth factor, interferon-γ, and interleukin-4 on peripheral nerve regeneration. J Biol Eng. 2019;13:86. doi: https://doi.org/10.1186/s13036-019-0216-x

Liu Y, Wang H. Peripheral nerve injury induced changes in the spinal cord and strategies to counteract/enhance the changes to promote nerve regeneration. Neural Regen Res. 2020;15(2):189-98. doi: https://doi.org/10.4103/1673-5374.265540

Zha K, Yang Y, Tian G, Sun Z, Yang Z, Li X, et al. Nerve growth factor (NGF) and NGF receptors in mesenchymal stem/stromal cells: Impact on potential therapies. Stem Cells Transl Med. 2021;10(7):1008-20. doi: https://doi.org/10.1002/sctm.20-0290

Pua LJ, Mai CW, Chung FF, Khoo AS, Leong CO, Lim WM, et al. Functional Roles of JNK and p38 MAPK Signaling in Nasopharyngeal Carcinoma. Int J Mol Sci. 2022;23(3):1108. doi: https://doi.org/10.3390/ijms23031108

Su H, Xu F, Sun H, Fu X, Zhao Y. Preparation and Evaluation of BDNF Composite Conduits for Regeneration of Sciatic Nerve Defect in Rats. J Pharm Sci. 2020;109(7):2189-95. doi: https://doi.org/10.1016/j.xphs.2020.03.027

Ahmed S, Kwatra M, Gawali B, Panda SR, Naidu VG. Potential role of TrkB agonist in neuronal survival by promoting CREB/BDNF and PI3K/Akt signaling in vitro and in vivo model of 3-nitropropionic acid (3-NP)-induced neuronal death. Apoptosis. 2021;26(1-2):52-70. doi: https://doi.org/10.1007/s10495-020-01645-x

Jones EJ, Chiou SY, Atherton PJ, Phillips BE, Piasecki M. Ageing and exercise-induced motor unit remodelling. J Physiol. 2022;600(8):1839-49. doi: https://doi.org/10.1113/JP281726

Pradhan J, Noakes PG, Bellingham MC. The Role of Altered BDNF/TrkB Signaling in Amyotrophic Lateral Sclerosis. Front Cell Neurosci. 2019;13:368. doi: https://doi.org/10.3389/fncel.2019.00368

McGregor CE, English AW. The Role of BDNF in Peripheral Nerve Regeneration: Activity-Dependent Treatments and Val66Met. Front Cell Neurosci. 2019;12:522. doi: https://doi.org/10.3389/fncel.2018.00522

Naji A, Eitoku M, Favier B, Deschaseaux F, Rouas-Freiss N, Suganuma N. Biological functions of mesenchymal stem cells and clinical implications. Cell Mol Life Sci. 2019;76(17):3323-48. doi: https://doi.org/10.1007/s00018-019-03125-1

Shekari A, Mahadeo C, Sanwalka N, Fahnestock M. Neurotrophins and cell death. In: Neurodevelopmental Pediatrics. Cham: Springer International Publishing; 2023. p. 55-75. doi: https://doi.org/10.1007/978-3-031-20792-1_4

Lopes B, Sousa P, Alvites R, Branquinho M, Sousa AC, Mendonça C, et al. Peripheral Nerve Injury Treatments and Advances: One Health Perspective. Int J Mol Sci. 2022;23(2):918. doi: https://doi.org/10.3390/ijms23020918

Hanwright PJ, Qiu C, Rath J, Zhou Y, von Guionneau N, Sarhane KA, et al. Sustained IGF-1 delivery ameliorates effects of chronic denervation and improves functional recovery after peripheral nerve injury and repair. Biomaterials. 2022;280:121244. doi: https://doi.org/10.1016/j.biomaterials.2021.121244

Tan Q, Li J, Yin Y, Shao W. The Role of Growth Factors in the Repair of Motor Injury. Front Pharmacol. 2022;13:898152. doi: https://doi.org/10.3389/fphar.2022.898152

Ahmad SS, Ahmad K, Lee EJ, Lee YH, Choi I. Implications of Insulin-Like Growth Factor-1 in Skeletal Muscle and Various Diseases. Cells. 2020;9(8):1773. doi: https://doi.org/10.3390/cells9081773

Chidambaram S, Velloso FJ, Rothbard DE, Deshpande K, Cajuste Y, Snyder KM, et al. Subventricular zone adult mouse neural stem cells require insulin receptor for self-renewal. Stem Cell Reports. 2022;17(6):1411-27. doi: https://doi.org/10.1016/j.stemcr.2022.04.007

Guo H, Chen P, Luo R, Zhang Y, Xu X, Gou X. The Roles of Ciliary Neurotrophic Factor – from Neuronutrition to Energy Metabolism. Protein Pept Lett. 2022;29(10):815-28. doi: https://doi.org/10.2174/0929866529666220905105800

Liu X, Hao F, Hao P, Zhang J, Wang L, You SW, et al. Regeneration and functional recovery of the completely transected optic nerve in adult rats by CNTF-chitosan. Signal Transduct Target Ther. 2023;8(1):81. doi: https://doi.org/10.1038/s41392-022-01289-0

Mashanov V, Alwan A, Kim MW, Lai D, Poerio A, Ju YM, et al. Synergistic effect of CNTF and GDNF on directed neurite growth in chick embryo dorsal root ganglia. PLoS One. 2020;15(10):e0240235. doi: https://doi.org/10.1371/journal.pone.0240235

Ma F, Wang H, Yang X, Wu Y, Liao C, Xie B, et al. Controlled release of ciliary neurotrophic factor from bioactive nerve grafts promotes nerve regeneration in rats with facial nerve injuries. J Biomed Mater Res A. 2022;110(4):788-96. doi: https://doi.org/10.1002/jbm.a.37327

Ji-Wei S, Zi-Ying L, Xiang T, Yang Y, Ju-Fen Z, Qing-Hua Z. CNTF induces Clcf1 in astrocytes to promote the differentiation of oligodendrocyte precursor cells. Biochem Biophys Res Commun. 2022;636(Pt 1):170-7. doi: https://doi.org/10.1016/j.bbrc.2022.10.013

Porzionato A, Barbon S, Stocco E, Dalzoppo D, Contran M, De Rose E, et al. Development of Oxidized Polyvinyl Alcohol-Based Nerve Conduits Coupled with the Ciliary Neurotrophic Factor. Materials (Basel). 2019;12(12):1996. doi: https://doi.org/10.3390/ma12121996

Wen SY, Li AM, Mi KQ, Wang RZ, Li H, Liu HX, et al. In vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity. Neural Regen Res. 2017;12(10):1716-23. doi: https://doi.org/10.4103/1673-5374.217352

Cui W, Liu CX, Wang J, Zhang YC, Shen Q, Feng ZH, et al. An oleanolic acid derivative reduces denervation-induced muscle atrophy via activation of CNTF-mediated JAK2/STAT3 signaling pathway. Eur J Pharmacol. 2019;861:172612. doi: https://doi.org/10.1016/j.ejphar.2019.172612

Fan L, Xiong Y, Fu Z, Xu D, Wang L, Chen Y, et al. Polyaniline promotes peripheral nerve regeneration by enhancement of the brainderived neurotrophic factor and ciliary neurotrophic factor expression and activation of the ERK1/2/MAPK signaling pathway. Mol Med Rep. 2017;16(5):7534-40. doi: https://doi.org/10.3892/mmr.2017.7534

Hu Z, Deng N, Liu K, Zhou N, Sun Y, Zeng W. CNTF-STAT3-IL-6 Axis Mediates Neuroinflammatory Cascade across Schwann Cell-Neuron-Microglia. Cell Rep. 2020;31(7):107657. doi: https://doi.org/10.1016/j.celrep.2020.107657

Cintrón-Colón AF, Almeida-Alves G, Boynton AM, Spitsbergen JM. GDNF synthesis, signaling, and retrograde transport in motor neurons. Cell Tissue Res. 2020;382(1):47-56. doi: https://doi.org/10.1007/s00441-020-03287-6

Nicoletti VG, Pajer K, Calcagno D, Pajenda G, Nógrádi A. The Role of Metals in the Neuroregenerative Action of BDNF, GDNF, NGF and Other Neurotrophic Factors. Biomolecules. 2022;12(8):1015. doi: https://doi.org/10.3390/biom12081015

Duarte Azevedo M, Sander S, Tenenbaum L. GDNF, A Neuron-Derived Factor Upregulated in Glial Cells during Disease. J Clin Med. 2020;9(2):456. doi: https://doi.org/10.3390/jcm9020456

Eggers R, de Winter F, Arkenaar C, Tannemaat MR, Verhaagen J. Enhanced regeneration and reinnervation following timed GDNF gene therapy in a cervical ventral root avulsion. Exp Neurol. 2019;321:113037. doi: https://doi.org/10.1016/j.expneurol.2019.113037

Ibáñez CF, Andressoo JO. Biology of GDNF and its receptors – Relevance for disorders of the central nervous system. Neurobiol Dis. 2017;97(Pt B):80-9. doi: https://doi.org/10.1016/j.nbd.2016.01.021

Lackington WA, Kočí Z, Alekseeva T, Hibbitts AJ, Kneafsey SL, Chen G, et al. Controlling the dose-dependent, synergistic and temporal effects of NGF and GDNF by encapsulation in PLGA microparticles for use in nerve guidance conduits for the repair of large peripheral nerve defects. J Control Release. 2019;304:51-64. doi: https://doi.org/10.1016/j.jconrel.2019.05.001

El Soury M, Gambarotta G. Soluble neuregulin-1 (NRG1): a factor promoting peripheral nerve regeneration by affecting Schwann cell activity immediately after injury. Neural Regen Res. 2019;14(8):1374-5. doi: https://doi.org/10.4103/1673-5374.253516

Fornasari BE, El Soury M, Nato G, Fucini A, Carta G, Ronchi G, et al. Fibroblasts Colonizing Nerve Conduits Express High Levels of Soluble Neuregulin1, a Factor Promoting Schwann Cell Dedifferentiation. Cells. 2020;9(6):1366. doi: https://doi.org/10.3390/cells9061366

Ronchi G, Raimondo S. Chronically denervated distal nerve stump inhibits peripheral nerve regeneration. Neural Regen Res. 2017;12(5):739-40. doi: https://doi.org/10.4103/1673-5374.206638

Farkas JE, Monaghan JR. A brief history of the study of nerve dependent regeneration. Neurogenesis (Austin). 2017;4(1):e1302216. doi: https://doi.org/10.1080/23262133.2017.1302216

Additional Files

Published

2024-08-30

How to Cite

1.
Nevmerzhytska NM, Yaremenko LM, Grabovyi OM. The role of mesenchymal stem cells in peripheral nerve regeneration. Pathologia [Internet]. 2024Aug.30 [cited 2024Sep.15];21(2):170-6. Available from: http://pat.zsmu.edu.ua/article/view/297836