全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用：99美元
投递稿件

查看量下载量

相关文章

更多...

椎间盘退变的机制及其治疗综述
The Mechanism and Treatment of Intervertebral Disc Degeneration

DOI: 10.12677/ACM.2020.1010347, PP. 2302-2310

Keywords: 椎间盘，退变，治疗
Intervertebral Disc, Degeneration, Treatment

Full-Text   Cite this paper   Add to My Lib

Abstract:

椎间盘退变(intervertebral disc degeneration, IVDD)是一个多因素的过程，其表现为表型和基因型的变化，导致椎管狭窄、脊柱不稳、腰腿痛等疾病。合成代谢与分解代谢的长期失衡导致椎间盘蛋白多糖和水合作用的逐渐丧失进而改变其组成，最终导致IVDD。目前对IVDD的处理只能缓解症状，无法从根本上解决椎间盘退变的情况。研究人员正在尝试确定造成椎间盘退变的各种因素以及再生策略。近期生物学方法在IVDD领域获得了推动力。本综述讲述了目前对椎间盘退变的理解，旨在提出促进椎间盘再生策略以及不同生物疗法的最新进展，如生长因子、细胞和基因疗法，这些疗法的潜力及结果也被广泛讨论。最初，椎间盘退变的治疗包括传统的保守治疗和手术治疗，通过人们不断地努力，将来生长因子、细胞和基因疗法可能被证明是非常有效的治疗IVDD的方法。
Intervertebral disc degeneration is a multifactorial process, which manifests as changes in phenotype and genotype, leading to spinal stenosis, spinal instability, low back pain and other diseases. The long-term imbalance between anabolism and catabolism leads to the gradual loss of intervertebral disc proteoglycan and hydration, which changes its composition and ultimately leads to IVDD. The current treatment of IVDD can only relieve symptoms, and cannot fundamentally solve the situation of intervertebral disc degeneration. Researchers are trying to determine the various factors that cause intervertebral disc degeneration and regeneration strategies. Recent biological methods have gained momentum in the field of IVDD. This review describes the current understanding of intervertebral disc degeneration, and aims to propose strategies to promote intervertebral disc regeneration and the latest advances in different biological therapies, such as growth factors, cell and gene therapies. The potential and results of these therapies have also been widely discussed. Initially, the treatment of intervertebral disc degeneration included traditional conservative treatment and surgical treatment. Through continuous efforts, growth factor, cell and gene therapy may prove to be very effective treatments for IVDD in the future.

References

[1]  Mirza, S.K. and White, A.A. III (1995) Anatomy of Intervertebral Disc and Pathophysiology of Herniated Disc Disease. Journal of Clinical Laser Medicine & Surgery, 13, 131-142.
https://doi.org/10.1089/clm.1995.13.131
[2]  Buckwalter, J.A. (1995) Aging and Degeneration of the Human Intervertebral Disc. Spine (Phila Pa 1976), 20, 1307-1314.
https://doi.org/10.1097/00007632-199506000-00022
[3]  Dowdell, J., Erwin, M., Choma, T., et al. (2017) Intervertebral Disk Degeneration and Repair. Neurosurgery, 80, S46-S54.
https://doi.org/10.1093/neuros/nyw078
[4]  Hemanta, D., Jiang, X.X., Feng, Z.Z., et al. (2016) Etiology for Degenerative Disc Disease. Chinese Medical Sciences Journal, 31, 185-191.
https://doi.org/10.1016/S1001-9294(16)30049-9
[5]  Mayer, J.E., Iatridis, J.C., Chan, D., et al. (2013) Review: Genetic Polymorphisms Associated with Intervertebral Disc Degeneration. Spine Journal, 13, 299-317.
https://doi.org/10.1016/j.spinee.2013.01.041
[6]  Seki, S., Kawaguchi, Y., Chiba, K., et al. (2005) A Functional SNP in CILP, Encoding Cartilage Intermediate Layer Protein, Is Associated with Susceptibility to Lumbar Disc Disease. Nature Genetics, 37, 607-612.
https://doi.org/10.1038/ng1557
[7]  Videman, T., Saarela, J., Kaprio, J., et al. (2009) Associations of 25 Structural, Degradative, and Inflammatory Candidate Genes with Lumbar Disc Desiccation, Bulging, and Height Narrowing. Arthritis & Rheumatology, 4, 470-481.
https://doi.org/10.1002/art.24268
[8]  Risbud, M.V. and Shapiro, I.M. (2014) Role of Cytokines in Intervertebral Disc Degeneration: Pain and Disc Content. Nature Reviews Rheumatology, 10, 44-56.
https://doi.org/10.1038/nrrheum.2013.160
[9]  Rizvi, M.R. (2015) Novel Treatment Strategies for Intervertebral Disc Degeneration. Saudi Journal for Health Sciences, 4, 5-15.
https://doi.org/10.4103/2278-0521.151403
[10]  Hayflick, L. (1965) The Limited in Vitro Lifetime of Human Diploid Cell Strains. Experimental Cell Research, 37, 614-636.
https://doi.org/10.1016/0014-4827(65)90211-9
[11]  Kepler, C.K., Ponnappan, R.K., Tannoury, C.A., et al. (2013) The Molecular Basis of Intervertebral Disc Degeneration. Spine Journal, 13, 318-330.
https://doi.org/10.1016/j.spinee.2012.12.003
[12]  Feng, C., Liu, H., Yang, M., et al. (2016) Disc Cell Senescence in Intervertebral Disc Degeneration: Causes and Molecular Pathways. Cell Cycle, 15, 1674-1684.
https://doi.org/10.1080/15384101.2016.1152433
[13]  Ding, F., Shao, Z., Xiong, L., et al. (2013) Cell Death in Intervertebral Disc Degeneration. Apoptosis, 18, 777-785.
https://doi.org/10.1007/s10495-013-0839-1
[14]  Blanquer, S.B.G., Grijpma, D.W., Poot, A.A., et al. (2015) Delivery Systems for the Treatment of Degenerated Intervertebral Discs. Advanced Drug Delivery Reviews, 84, 172-187.
https://doi.org/10.1016/j.addr.2014.10.024
[15]  Molinos, M., Almeida, C.R., Caldeira, J., et al. (2015) Inflammation in Intervertebral Disc Degeneration and Regeneration. Journal of the Royal Society Interface, 12, Article ID: 20141191.
https://doi.org/10.1098/rsif.2014.1191
[16]  Boni, M. and Denaro, V. (1987) Anatomo-Clinical Correlations in Cervical Spondylosis. In: Kehr, P. and Weidner, A., Eds., Cervical Spine, Springer-Verlag, Berlin, Vol. 1, 3-20.
https://doi.org/10.1007/978-3-7091-8882-8_1
[17]  Lotz, J.C. and Ulrich, J.A. (2006) Innervation, Inflammation, and Hypermobility May Characterize Pathologic Disc Degeneration. Review of Animal Model Data. The Journal of Bone and Joint Surgery. American Volume, 88, 76-82.
https://doi.org/10.2106/00004623-200604002-00016
[18]  Yoon, S.T. (2005) Molecular Therapy of the Intervertebral Disc. Spine Journal, 5, S280-S286.
https://doi.org/10.1016/j.spinee.2005.02.017
[19]  Tow, B.P., Hsu, W.K., Wang, J.C., et al. (2007) Disc Regeneration: A Glimpse of the Future. Clinical Neurosurgery, 54, 122-128.
[20]  Navani, A., Ambach, M.A., Wei, J.J., et al. (2017) Biologic Therapies for Intervertebral Degenerative Disc Disease: A Review of Novel Applications. Journal of Stem Cells Research, Reviews & Reports, 4, 10-23.
[21]  Kadow, T., Sowa, G., Vo, N., et al. (2015) Molecular Basis of Intervertebral Disc Degeneration and Herniations: What Are the Important Translational Questions? Clinical Orthopaedics and Related Research, 473, 1903-1912.
https://doi.org/10.1007/s11999-014-3774-8
[22]  Radcliff, K.E., Kepler, C.K., Jakoi, A., et al. (2013) Adjacent Segment Disease in the Lumbar Spine Following Different Treatment Interventions. Spine Journal, 13, 1339-1349.
https://doi.org/10.1016/j.spinee.2013.03.020
[23]  Vadala, G., Russo, F., Ambrosio, L., et al. (2016) Stem Cells Sources for Intervertebral Disc Regeneration. World Journal of Stem Cells, 8, 185-201.
https://doi.org/10.4252/wjsc.v8.i5.185
[24]  Masuda, K. and An, H.S. (2004) Growth Factors and the Intervertebral Disc. Spine Journal, 4, 330S-340S.
https://doi.org/10.1016/j.spinee.2004.07.028
[25]  田海泉, 李放. 生长因子在椎间盘退行性变组织修复重建中的意义[J]. 中国组织工程研究与临床康复, 2008, 12(46): 9121-9125.
[26]  马健, 李放, 任大江, 等. 富含血小板血浆凝胶复合脂肪间充质干细胞构建可注射组织工程髓[J]. 中国脊柱脊髓杂志, 2011(5): 353-357.
[27]  Chen, W.H., Lo, W.C., Lee, J.J., et al. (2006) Tissue-Engineered Intervertebral Disc and Chondrogenesis Using Human Nucleus Pulposus Regulated through TGF-beta1 in Platelet-Rich Plasma. Journal of Cellular Physiology, 209, 744-754.
https://doi.org/10.1002/jcp.20765
[28]  王彦超, 席志鹏, 谢林. 细胞疗法是修复退变椎间盘最有前景的技术[J]. 中国组织工程研究, 2017, 21(20): 3234-3240.
[29]  Mwale, F., Roughley, P., Antoniou, J., et al. (2004) Distinction between the Extracellular Matrix of the Nucleus Pulposus and Hyaline Cartilage: A Requisite for Tissue Engineering of Intervertebral Disc. European Cells & Materials, 8, 58-63.
https://doi.org/10.22203/eCM.v008a06
[30]  南利平, 冯新民, 张亮, 等. 干细胞在椎间盘退变生物学治疗中的研究进展[J]. 中华损伤与修复杂志(电子版), 2018, 13(2): 134-138.
[31]  Sobajima, S., Kim, J.S., Gilbertson, L.G., et al. (2004) Gene Therapy for Degenerative Disc Disease. Gene Therapy, 11, 390-401.
https://doi.org/10.1038/sj.gt.3302200
[32]  肖剑. 重组腺病毒介导的人转化生长因子β1基因调节椎问盘生物功能的实验研究[D]: [博士学位论文]. 上海: 第二军医大学, 2002.
[33]  Paul, R., Haydon, R.C., Cheng, H.W., et al. (2003) Potential Use of Sox9 Gene Therapy for Intervertebral Degenerative Disc Disease. Spine (Phila Pa 1976), 28, 755-763.
https://doi.org/10.1097/01.BRS.0000058946.64222.92
[34]  Wang, H., Kroeber, M., Hanke, M., et al. (2004) Release of Active and Depot GDF-5 after Adenovirus Mediated over Expression Stimulates Rabbit and Human Intervertebral Disc Cells. Journal of Molecular Medicine, 82, 126-134.
https://doi.org/10.1007/s00109-003-0507-y
[35]  Cui, M., Wan, Y., Anderson, D.G., et al. (2008) Mouse Growth and Differentiation Factor-5 Protein and DNA Therapy Potentiates Intervertebral Disc Cell Aggregation and Chondrogenic Gene Expression. Spine Journal, 8, 287-295.
https://doi.org/10.1016/j.spinee.2007.05.012
[36]  Yoon, S.T., Park, J.S., Kim, K.S., et al. (2004) ISSLS Prize Winner: LMP-1 Upregulates Intervertebral Disc Cell Production of Proteoglycans and BMPs in Vitro and in Vivo. Spine, 29, 2603-2611.
https://doi.org/10.1097/01.brs.0000146103.94600.85
[37]  Moon, S.H., Nishida, K., Gilbertson, L.G., et al. (2008) Biologic Response of Human Intervertebral Disc Cells to Gene Therapy Cocktail. Spine (Phila Pa 1976), 33, 1850-1855.
https://doi.org/10.1097/BRS.0b013e31817e1cd7
[38]  王珏, 王义生, 刘宏建. 腺病毒介导的骨形态发生蛋白-2对兔退变椎间盘组织Sox9基因的影响[J]. 中华实验外科杂志, 2011, 28(8): 1378-1380.
[39]  Douglas, J.T. (2007) Adenoviral Vectors for Gene Therapy. Molecular Biotechnology, 36, 71-80.
https://doi.org/10.1007/s12033-007-0021-5
[40]  Tripathy, S.K., Black, H.B. and Goldwasser, E. (1996) Immune Responses to Transgene-Encoded Proteins Limit the Stability of Gene Expression after Injection of Replication-Defective Adenovirus Vectors. Nature Medicine, 2, 545-550.
https://doi.org/10.1038/nm0596-545
[41]  Lattermann, C., Oxner, W.M. and Xiao, X. (2005) The Adeno Associated Viral Vector as a Strategy for Intradiscal Gene Transfer in Immune Competent and Pre-Exposed Rabbit. Spine (Phila Pa 1976), 30, 497-504.
https://doi.org/10.1097/01.brs.0000154764.62072.44
[42]  Ren, S., Liu, Y. and Ma, J. (2013) Treatment of Rabbit Intervertebral Disc Degeneration with Co-Transfection by Adeno-Associated Virus-Mediated SOX9 and Osteogenic Protein-1 Double Genes in Vivo. International Journal of Molecular Medicine, 32, 1063-1068.
https://doi.org/10.3892/ijmm.2013.1497
[43]  谌平, 何成宜, 陈志英. 非病毒载体在基因治疗中的发展与应用[J]. 集成技术, 2017, 6(2): 59-65.
[44]  Chung, S.A., Wei, A.Q., Connor, D.E., et al. (2007) Nucleus Pulposus Cellular Longevity by Telomerase Gene Therapy. Spine (Phila Pa 1976), 32, 1188-1196.
https://doi.org/10.1097/BRS.0b013e31805471a3
[45]  Nishida, K., Doita, M., Takada, T., et al. (2006) Sustained Transgene Expression in Intervertebral Disc Cells in Vivo Mediated by Microbubble-Enhanced Ultrasound Gene Therapy. Spine (Phila Pa 1976), 31, 1415-1419.
https://doi.org/10.1097/01.brs.0000219945.70675.dd
[46]  Ferree, B. (2003) Use of Extracellular Matrix Tissue to Preserve Cultured Cell Phenotype. Google Patents, 2003-02-06.
[47]  张丽, 关晓明, 马迅, 等. 人端粒酶反转录酶基因感染对人髓核细胞基本特性的影响[J]. 中国药物与临床, 2013, 13(Z1): 1-3.
[48]  Xin, H., Zhang, C., Wang, D., et al. (2013) Tissue-Engineered Allograft Intervertebral Disc Transplantation for the Treatment of Degenerative Disc Disease: Experimental Study in a Beagle Model. Tissue Engineering Part A, 19, 143-151.
https://doi.org/10.1089/ten.tea.2012.0255
[49]  Yi, Z., et al. (2014) Effects of Transplantation of hTIMP1-Expressing Bone Marrow Mesenchymal Stem Cells on the Extracellular Matrix of Degenerative Intervertebral Discs in an in Vivo Rabbit Model. Spine, 39, E669-E675.
https://doi.org/10.1097/BRS.0000000000000316
[50]  Lu, K., Li, H., Yang, K., et al. (2017) Exosomes as Potential Alternatives to Stem Cell Therapy for Intervertebral Disc Degeneration: In-Vitro Study on Exosomes in Interaction of Nucleus Pulposus Cells and Bone Marrow Mesenchymal Stem Cells. Stem Cell Research & Therapy, 8, 108.
https://doi.org/10.1186/s13287-017-0563-9
[51]  Ren, X.F., Diao, Z.Z., Xi, Y.M., et al. (2015) Adeno-Associated Virus-Mediated BMP-7 and SOX9 in Vitro Co-Transfection of Human Degenerative Intervertebral Disc Cells. Genetics and Molecular Research, 14, 3736-3744.
https://doi.org/10.4238/2015.April.22.1
[52]  Li, W., Wang, P., Zhang, Z., et al. (2017) MiR-184 Regulates Proliferation in Nucleus Pulposus Cells by Targeting GAS1. World Neurosurgery, 97, 710-715.
https://doi.org/10.1016/j.wneu.2016.01.024

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133