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Journal of Neurorestoratology  2019, Vol. 7 Issue (4): 196-206    doi: 10.26599/JNR.2019.9040024
Review Article     
Progress in research into spinal cord injury repair: Tissue engineering scaffolds and cell transdifferentiation
Changke Ma1, Peng Zhang2, Yixin Shen2,(✉)
1 Department of Orthopaedics, The People's Hospital of Luhe, Nanjing 211500, Jiangsu, China
2 Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China
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Abstract  

As with all tissues of the central nervous system, the low regeneration ability of spinal cord tissue after injury decreases the potential for repair and recovery. Initially, in spinal cord injuries (SCI), often the surgeon can only limit further damage by early surgical decompression. However, with the development of basic science, especially the development of genetic engineering, molecular biology, tissue engineering, and materials science, some promising progress has been made in promoting the repair of central nervous system injuries. For example, transplantation of neural stem cells (NSCs), olfactory ensheathing cells (OECs), and gene- mediated transdifferentiation to repair central nervous system injury. This paper summarizes the progress and prospects of SCI repair with tissue engineering scaffold and cell transdifferentiation from an extensive literatures.



Key wordsspinal cord injury      stem cells      olfactory ensheathing cells      hydrogel      transdifferentiation     
Received: 19 September 2019      Published: 17 January 2020
Corresponding Authors: Yixin Shen   
Cite this article:

Changke Ma, Peng Zhang, Yixin Shen. Progress in research into spinal cord injury repair: Tissue engineering scaffolds and cell transdifferentiation. Journal of Neurorestoratology, 2019, 7: 196-206.

URL:

http://jnr.tsinghuajournals.com/10.26599/JNR.2019.9040024     OR     http://jnr.tsinghuajournals.com/Y2019/V7/I4/196

[1]   Smith AE, Molton IR, Jensen MP. Self-reported incidence and age of onset of chronic comorbid medical conditions in adults aging with long-term physical disability. Disabil Health J. 2016, 9(3): 533-538.
[2]   Street JT, Noonan VK, Cheung A, et al. Incidence of acute care adverse events and long-term health-related quality of life in patients with TSCI. Spine J. 2015, 15(5): 923-932.
[3]   Chikuda H, Ohya J, Horiguchi H, et al. Ischemic stroke after cervical spine injury: analysis of 11, 005 patients using the Japanese diagnosis procedure combination database. Spine J. 2014, 14(10): 2275-2280.
[4]   Piran S, Schulman S. Incidence and risk factors for venous thromboembolism in patients with acute spinal cord injury: A retrospective study. Thromb Res. 2016, 147: 97-101.
[5]   Li G, Che MT, Zeng X, et al. Neurotrophin-3 released from implant of tissue-engineered fibroin scaffolds inhibits inflammation, enhances nerve fiber regeneration, and improves motor function in canine spinal cord injury. J Biomed Mater Res. 2018, 106(8): 2158-2170.
[6]   Anderson MA, Burda JE, Ren YL, et al. Astrocyte scar formation aids central nervous system axon regeneration. Nature. 2016, 532(7598): 195-200.
[7]   Schwab ME, Br?samle C. Regeneration of lesioned corticospinal tract fibers in the adult rat spinal cord under experimental conditions. Spinal Cord. 1997, 35(7): 469-473.
[8]   Shafiee A, Atala A. Printing technologies for medical applications. Trends Mol Med. 2016, 22(3): 254-265.
[9]   Wang LJ, Shi Q, Dai JW, et al. Increased vascularization promotes functional recovery in the transected spinal cord rats by implanted vascular endothelial growth factor-targeting collagen scaffold. J Orthop Res. 2018, 36(3): 1024-1034.
[10]   Hong LTA, Kim YM, Park HH, et al. An injectable hydrogel enhances tissue repair after spinal cord injury by promoting extracellular matrix remodeling. Nat Commun. 2017, 8(1): 533.
[11]   Boido M, Ghibaudi M, Gentile P, et al. Chitosan- based hydrogel to support the paracrine activity of mesenchymal stem cells in spinal cord injury treatment. Sci Rep. 2019, 9(1): 6402.
[12]   Deumens R, Koopmans GC, Honig WM, et al. Chronically injured corticospinal axons do not cross large spinal lesion gaps after a multifactorial transplantation strategy using olfactory ensheathing cell/ olfactory nerve fibroblast-biomatrix bridges. J Neurosci Res. 2006, 83(5): 811-820.
[13]   Cigognini D, Silva D, Paloppi S, et al. Evaluation of mechanical properties and therapeutic effect of injectable self-assembling hydrogels for spinal cord injury. J Biomed Nanotechnol. 2014, 10(2): 309-323.
[14]   Ghosh B, Nong J, Wang ZC, et al. A hydrogel engineered to deliver minocycline locally to the injured cervical spinal cord protects respiratory neural circuitry and preserves diaphragm function. Neurobiol Dis. 2019, 127: 591-604.
[15]   Liu Y, Ye H, Satkunendrarajah K, et al. A self- assembling peptide reduces glial scarring, attenuates post-traumatic inflammation and promotes neurological recovery following spinal cord injury. Acta Biomater. 2013, 9(9): 8075-8088.
[16]   Rauch MF, Hynes SR, Bertram J, et al. Engineering angiogenesis following spinal cord injury: a coculture of neural progenitor and endothelial cells in a degradable polymer implant leads to an increase in vessel density and formation of the blood-spinal cord barrier. Eur J Neurosci. 2009, 29(1): 132-145.
[17]   Arulmoli J, Wright HJ, Phan DTT, et al. Combination scaffolds of salmon fibrin, hyaluronic acid, and laminin for human neural stem cell and vascular tissue engineering. Acta Biomater. 2016, 43: 122-138.
[18]   Xue L, Greisler HP. Angiogenic effect of fibroblast growth factor-1 and vascular endothelial growth factor and their synergism in a novel in vitro quantitative fibrin-based 3-dimensional angiogenesis system. Surgery. 2002, 132(2): 259-267.
[19]   Kroon ME, van Schie ML, van der Vecht B, et al. Collagen type 1 retards tube formation by human microvascular endothelial cells in a fibrin matrix. Angiogenesis. 2002, 5(4): 257-265.
[20]   Chedly J, Soares S, Montembault A, et al. Physical chitosan microhydrogels as scaffolds for spinal cord injury restoration and axon regeneration. Biomaterials. 2017, 138: 91-107.
[21]   Zeng CG, Xiong Y, Xie GY, et al. Fabrication and evaluation of PLLA multichannel conduits with nanofibrous microstructure for the differentiation of NSCs in vitro. Tissue Eng Part A. 2014, 20(5/6): 1038-1048.
[22]   Zeng X, Zeng YS, Ma YH, et al. Bone marrow mesenchymal stem cells in a three-dimensional gelatin sponge scaffold attenuate inflammation, promote angiogenesis, and reduce cavity formation in experimental spinal cord injury. Cell Transplant. 2011, 20(11/12): 1881-1899.
[23]   Jalali Monfared M, Nasirinezhad F, Ebrahimi-Barough S, et al. Transplantation of miR-219 overexpressed human endometrial stem cells encapsulated in fibrin hydrogel in spinal cord injury. J Cell Physiol. 2019, 234(10): 18887-18896.
[24]   Duan HM, Ge WH, Zhang AF, et al. Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury. Proc Natl Acad Sci USA. 2015, 112(43): 13360-13365.
[25]   Ko HR, Kwon IS, Hwang I, et al. Akt1-Inhibitor of DNA binding2 is essential for growth cone formation and axon growth and promotes central nervous system axon regeneration. Elife. 2016, 5: e20799.
[26]   Neumann S, Woolf CJ. Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury. Neuron. 1999, 23(1): 83-91.
[27]   Epstein Y, Perry N, Volin M, et al. MiR-9a modulates maintenance and ageing of Drosophila germline stem cells by limiting N-cadherin expression. Nat Commun. 2017, 8(1): 600.
[28]   Wang TY, Yuan WQ, Liu Y, et al. MiR-142-3p is a potential therapeutic target for sensory function recovery of spinal cord injury. Med Sci Monit. 2015, 21: 2553-2556.
[29]   Wang TY, Liu Y, Yuan WQ, et al. Identification of microRNAome in rat bladder reveals miR-1949 as a potential inducer of bladder cancer following spinal cord injury. Mol Med Rep. 2015, 12(2): 2849-2857.
[30]   Hauk TG, Leibinger M, Müller A, et al. Stimulation of axon regeneration in the mature optic nerve by intravitreal application of the toll-like receptor 2 agonist Pam3Cys. Invest Ophthalmol Vis Sci. 2010, 51(1): 459-464.
[31]   Nagata K, Hama I, Kiryu-Seo S, et al. MicroRNA-124 is down regulated in nerve-injured motor neurons and it potentially targets mRNAs for KLF6 and STAT3. Neuroscience. 2014, 256: 426-432.
[32]   Kumar R, Sahu SK, Kumar M, et al. MicroRNA 17-5p regulates autophagy in Mycobacterium tuberculosis- infected macrophages by targeting Mcl-1 and STAT3. Cell Microbiol. 2016, 18(5): 679-691.
[33]   Hu JZ, Huang JH, Zeng L, et al. Anti-apoptotic effect of microRNA-21 after contusion spinal cord injury in rats. J Neurotrauma. 2013, 30(15): 1349-1360.
[34]   Sayed D, He MZ, Hong C, et al. MicroRNA-21 is a downstream effector of AKT that mediates its antiapoptotic effects via suppression of Fas ligand. J Biol Chem. 2010, 285(26): 20281-20290.
[35]   Bhalala OG, Pan LL, Sahni V, et al. MicroRNA-21 regulates astrocytic response following spinal cord injury. J Neurosci. 2012, 32(50): 17935-17947.
[36]   Song JL, Zheng W, Chen W, et al. Lentivirus- mediated microRNA-124 gene-modified bone marrow mesenchymal stem cell transplantation promotes the repair of spinal cord injury in rats. Exp Mol Med. 2017, 49(5): e332.
[37]   Dergham P, Ellezam B, Essagian C, et al. Rho signaling pathway targeted to promote spinal cord repair. J Neurosci. 2002, 22(15): 6570-6577.
[38]   Conrad S, Schluesener HJ, Trautmann K, et al. Prolonged lesional expression of RhoA and RhoB following spinal cord injury. J Comp Neurol. 2005, 487(2): 166-175.
[39]   Jee MK, Jung JS, Choi JI, et al. MicroRNA 486 is a potentially novel target for the treatment of spinal cord injury. Brain. 2012, 135(Pt 4): 1237-1252.
[40]   Tosh D, Slack JM. How cells change their phenotype. Nat Rev Mol Cell Biol. 2002, 3(3): 187-194.
[41]   Cie?lar-Pobuda A, Knoflach V, Ringh MV, et al. Transdifferentiation and reprogramming: Overview of the processes, their similarities and differences. Biochim Biophys Acta Mol Cell Res. 2017, 1864(7): 1359-1369.
[42]   Wada MR, Inagawa-Ogashiwa M, Shimizu S, et al. Generation of different fates from multipotent muscle stem cells. Development. 2002, 129(12): 2987-2995.
[43]   Xu J, Du YY, Deng HK. Direct lineage reprogramming: strategies, mechanisms, and applications. Cell Stem Cell. 2015, 16(2): 119-134.
[44]   Bierlein De la Rosa M, Sharma AD, Mallapragada SK, et al. Transdifferentiation of brain-derived neurotrophic factor (BDNF)-secreting mesenchymal stem cells significantly enhance BDNF secretion and Schwann cell marker proteins. J Biosci Bioeng. 2017, 124(5): 572-582.
[45]   Shen SW, Duan CL, Chen XH, et al. Neurogenic effect of VEGF is related to increase of astrocytes transdifferentiation into new mature neurons in rat brains after stroke. Neuropharmacology. 2016, 108: 451-461.
[46]   Wang S, Jung Y, Hyun J, et al. RNA binding proteins control transdifferentiation of hepatic stellate cells into myofibroblasts. Cell Physiol Biochem. 2018, 48(3): 1215-1229.
[47]   Prasad A, Teh DB, Shah Jahan FR, et al. Direct conversion through trans-differentiation: efficacy and safety. Stem Cells Dev. 2017, 26(3): 154-165.
[48]   Liu YG, Miao QL, Yuan JC, et al. Ascl1 converts dorsal midbrain astrocytes into functional neurons in vivo. J Neurosci. 2015, 35(25): 9336-9355.
[49]   Bonilla-Porras AR, Velez-Pardo C, Jimenez-Del-Rio M. Fast transdifferentiation of human Wharton’s jelly mesenchymal stem cells into neurospheres and nerve-Like cells. J Neurosci Methods. 2017, 282: 52-60.
[50]   Kleiderman S, Gutbier S, Ugur Tufekci K, et al. Conversion of nonproliferating astrocytes into neurogenic neural stem cells: control by FGF2 and interferon-Γ. Stem Cells. 2016, 34(12): 2861-2874.
[51]   Kurian L, Sancho-Martinez I, Nivet E, et al. Conversion of human fibroblasts to angioblast-Like progenitor cells. Nat Methods. 2013, 10(1): 77-83.
[52]   Lim MS, Chang MY, Kim SM, et al. Generation of dopamine neurons from rodent fibroblasts through the expandable neural precursor cell stage. J Biol Chem. 2015, 290(28): 17401-17414.
[53]   Doeser MC, Sch?ler HR, Wu GM. Reduction of fibrosis and scar formation by partial reprogramming in vivo. Stem Cells. 2018, 36(8): 1216-1225.
[54]   Pekny M, Wilhelmsson U, Tatlisumak T, et al. Astrocyte activation and reactive gliosis-A new target in stroke? Neurosci Lett. 2019, 689: 45-55.
[55]   Frik J, Merl-Pham J, Plesnila N, et al. Cross-talk between monocyte invasion and astrocyte proliferation regulates scarring in brain injury. EMBO Rep. 2018, 19(5): e45294.
[56]   Falo MC, Fillmore HL, Reeves TM, et al. Matrix metalloproteinase-3 expression profile differentiates adaptive and maladaptive synaptic plasticity induced by traumatic brain injury. J Neurosci Res. 2006, 84(4): 768-781.
[57]   Yin G, Du MJ, Li R, et al. Glia maturation factor beta is required for reactive gliosis after traumatic brain injury in zebrafish. Exp Neurol. 2018, 305: 129-138.
[58]   Chen CH, Zhong XL, Smith DK, et al. Astrocyte- specific deletion of Sox2 promotes functional recovery after traumatic brain injury. Cereb Cortex. 2019, 29(1): 54-69.
[59]   Faiz M, Sachewsky N, Gascón S, et al. Adult neural stem cells from the subventricular zone give rise to reactive astrocytes in the cortex after stroke. Cell Stem Cell. 2015, 17(5): 624-634.
[60]   Guo ZY, Zhang L, Wu Z, et al. In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer’s disease model. Cell Stem Cell. 2014, 14(2): 188-202.
[61]   Magnusson JP, G?ritz C, Tatarishvili J, et al. A latent neurogenic program in astrocytes regulated by Notch signaling in the mouse. Science. 2014, 346(6206): 237-241.
[62]   Sirko S, Behrendt G, Johansson PA, et al. Reactive Glia in the injured brain acquire stem cell properties in response to sonic hedgehog. [corrected]. Cell Stem Cell. 2013, 12(4): 426-439.
[63]   Cao L, Liu L, Chen ZY, et al. Olfactory ensheathing cells genetically modified to secrete GDNF to promote spinal cord repair. Brain. 2004, 127(Pt 3): 535-549.
[64]   Fouad K, Schnell L, Bunge MB, et al. Combining Schwann cell bridges and olfactory-ensheathing Glia grafts with chondroitinase promotes locomotor recovery after complete transection of the spinal cord. J Neurosci. 2005, 25(5): 1169-1178.
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