Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

Overview of Stem Cell Therapy in Intervertebral Disc Disease: Clinical Perspective

Author(s): Ayshe Hajiesmailpoor, Omid Mohamadi, Gholamreza Farzanegan, Payam Emami and Masoud Ghorbani*

Volume 18, Issue 5, 2023

Published on: 01 September, 2022

Page: [595 - 607] Pages: 13

DOI: 10.2174/1574888X17666220628123912

Price: $65

Abstract

Intervertebral Disc Degeneration (IDD) is recognized as an aging process, an important and most common pathological condition caused by an imbalance of anabolic and catabolic metabolisms in the Intervertebral Disc (IVD), and leads to changes in the Extracellular Matrix (ECM), impaired metabolic regulation of Nucleus Pulposus (NP), and increased oxidative stress. IDD is mostly associated with pain in the back and neck, which is referred to as a type of disability. Pharmacological and surgical interventions are currently used to treat IDD, but evidence has shown that these interventions do not have the ability to inhibit the progression of IDD and restore IVD function because IVD lacks the intrinsic capacity for regeneration. Thus, therapies that rely on a degenerative cell repair mechanism may be a viable alternative strategy. Biological interventions have been assessed by attempting to regenerate IVD by restoring ECM and cellular function. Over the past decade, stem cell-based therapies have been considered, and promising results have been obtained in various studies. Given this, we reviewed clinical trials and preliminary studies of biological disc repair with a focus on stem cell therapy-based therapies.

Keywords: Intervertebral disc degeneration , Intervertebral disc, Stem cell therapy, Biological therapy, Clinical trial, disc regeneration

Graphical Abstract

[1]
Pennicooke B, Moriguchi Y, Hussain I, Bonssar L, Härtl R. Biological treatment approaches for degenerative disc disease: A review of clinical trials and future directions. Cureus 2016; 8(11): e892.
[http://dx.doi.org/10.7759/cureus.892]
[2]
Sun Y, Leung VY, Cheung KM. Clinical trials of intervertebral disc regeneration: Current status and future developments. Int Orthop 2019; 43(4): 1003-10.
[http://dx.doi.org/10.1007/s00264-018-4245-8] [PMID: 30498908]
[3]
Pattappa G, Li Z, Peroglio M, Wismer N, Alini M, Grad S. Diversity of intervertebral disc cells: Phenotype and function. J Anat 2012; 221(6): 480-96.
[http://dx.doi.org/10.1111/j.1469-7580.2012.01521.x] [PMID: 22686699]
[4]
Choi Y-S. Pathophysiology of degenerative disc disease. Asian Spine J 2009; 3(1): 39-44.
[http://dx.doi.org/10.4184/asj.2009.3.1.39] [PMID: 20404946]
[5]
Maher C, Underwood M, Buchbinder R. Non-specific low back pain. Lancet 2017; 389(10070): 736-47.
[http://dx.doi.org/10.1016/S0140-6736(16)30970-9] [PMID: 27745712]
[6]
Krut Z, Pelled G, Gazit D, Gazit Z. Stem cells and exosomes: New therapies for intervertebral disc degeneration. Cells 2021; 10(9): 2241.
[http://dx.doi.org/10.3390/cells10092241] [PMID: 34571890]
[7]
Kloppenburg M, Berenbaum F. Osteoarthritis year in review 2019: Epidemiology and therapy. Osteoarthritis Cartilage 2020; 28(3): 242-8.
[http://dx.doi.org/10.1016/j.joca.2020.01.002] [PMID: 31945457]
[8]
Maldonado CV, Paz RD, Martin CB. Adjacent-level degeneration after cervical disc arthroplasty versus fusion. Eur Spine J 2011; 20 (Suppl. 3): 403-37.
[http://dx.doi.org/10.1007/s00586-011-1916-1]
[9]
Sugawara T, Itoh Y, Hirano Y, Higashiyama N, Mizoi K. Long term outcome and adjacent disc degeneration after anterior cervical discectomy and fusion with titanium cylindrical cages. Acta Neurochir (Wien) 2009; 151(4): 303-9.
[http://dx.doi.org/10.1007/s00701-009-0217-5] [PMID: 19262984]
[10]
Nagae M, Ikeda T, Mikami Y, et al. Intervertebral disc regeneration using platelet-rich plasma and biodegradable gelatin hydrogel microspheres. Tissue Eng 2007; 13(1): 147-58.
[http://dx.doi.org/10.1089/ten.2006.0042] [PMID: 17518588]
[11]
Chujo T, An HS, Akeda K, et al. Effects of growth differentiation factor-5 on the intervertebral disc - in vitro bovine study and in vivo rabbit disc degeneration model study. Spine 2006; 31(25): 2909-17.
[http://dx.doi.org/10.1097/01.brs.0000248428.22823.86] [PMID: 17139221]
[12]
Willems N, Bach FC, Plomp SG, et al. Intradiscal application of rhBMP-7 does not induce regeneration in a canine model of spontaneous intervertebral disc degeneration. Arthritis Res Ther 2015; 17(1): 137.
[http://dx.doi.org/10.1186/s13075-015-0625-2] [PMID: 26013758]
[13]
Matta A, Erwin WM. Injectable biologics for the treatment of degenerative disc disease. Curr Rev Musculoskelet Med 2020; 13(6): 680-7.
[http://dx.doi.org/10.1007/s12178-020-09668-2] [PMID: 32705541]
[14]
Huang Y-C, Xiao J, Leung VY, Lu WW, Hu Y, Luk KDK. Lumbar intervertebral disc allograft transplantation: The revascularisation pattern. Eur Spine J 2018; 27(3): 728-36.
[http://dx.doi.org/10.1007/s00586-017-5419-6] [PMID: 29214370]
[15]
Chan SC, Stoyanov J, Bertolo A, Zhang X, Guerrero J, Sakai D, et al. Fluorescence-activated cell sorting is more potent to fish intervertebral disk progenitor cells than magnetic and beads-based methods. Tissue Eng Part C Methods 2019; 25(10): 571-80.
[16]
Roberts S, Menage J, Urban JP. Biochemical and structural properties of the cartilage end-plate and its relation to the intervertebral disc. Spine 1989; 14(2): 166-74.
[http://dx.doi.org/10.1097/00007632-198902000-00005] [PMID: 2922637]
[17]
De Geer CM. Intervertebral disk nutrients and transport mechanisms in relation to disk degeneration: A narrative literature review. J Chiropr Med 2018; 17(2): 97-105.
[http://dx.doi.org/10.1016/j.jcm.2017.11.006] [PMID: 30166966]
[18]
Newell N, Little JP, Christou A, Adams MA, Adam CJ, Masouros SD. Biomechanics of the human intervertebral disc: A review of testing techniques and results. J Mech Behav Biomed Mater 2017; 69: 420-34.
[http://dx.doi.org/10.1016/j.jmbbm.2017.01.037] [PMID: 28262607]
[19]
Nedresky D, Reddy V, Singh G. Anatomy, back, nucleus pulposus 2018.
[20]
Maroudas A, Stockwell RA, Nachemson A, Urban J. Factors involved in the nutrition of the human lumbar intervertebral disc: Cellularity and diffusion of glucose in vitro. J Anat 1975; 120(Pt 1): 113-30.
[PMID: 1184452]
[21]
Bayliss MT, Johnstone B, O’Brien JP. 1988 Volvo award in basic science. Proteoglycan synthesis in the human intervertebral disc. Variation with age, region and pathology. Spine 1988; 13(9): 972-81.
[http://dx.doi.org/10.1097/00007632-198809000-00003] [PMID: 3206304]
[22]
Risbud MV, Shapiro IM. Notochordal cells in the adult intervertebral disc: New perspective on an old question. Critical Reviews™ in Eukaryotic Gene Expression 2011; 21(1)
[http://dx.doi.org/10.1615/CritRevEukarGeneExpr.v21.i1.30]
[23]
Fernandez-Moure J, Moore CA, Kim K, et al. Novel therapeutic strategies for degenerative disc disease: Review of cell biology and intervertebral disc cell therapy. SAGE Open Med 2018; 6: 2050312118761674.
[http://dx.doi.org/10.1177/2050312118761674] [PMID: 29568524]
[24]
Marchand F, Ahmed AM. Investigation of the laminate structure of lumbar disc anulus fibrosus. Spine 1990; 15(5): 402-10.
[http://dx.doi.org/10.1097/00007632-199005000-00011] [PMID: 2363068]
[25]
Hastreiter D, Ozuna RM, Spector M. Regional variations in certain cellular characteristics in human lumbar intervertebral discs, including the presence of α-smooth muscle actin. J Orthop Res 2001; 19(4): 597-604.
[http://dx.doi.org/10.1016/S0736-0266(00)00069-3] [PMID: 11518268]
[26]
Donohue PJ, Jahnke MR, Blaha JD, Caterson B. Characterization of link protein(s) from human intervertebral-disc tissues. Biochem J 1988; 251(3): 739-47.
[http://dx.doi.org/10.1042/bj2510739] [PMID: 3415643]
[27]
Cheung KM, Samartzis D, Karppinen J, Luk KD. Are “patterns” of lumbar disc degeneration associated with low back pain?: New insights based on skipped level disc pathology. Spine 2012; 37(7): E430-8.
[http://dx.doi.org/10.1097/BRS.0b013e3182304dfc] [PMID: 22466575]
[28]
Samartzis D, Karppinen J, Mok F, Fong DY, Luk KD, Cheung KM. A population-based study of juvenile disc degeneration and its association with overweight and obesity, low back pain, and diminished functional status. J Bone Joint Surg Am 2011; 93(7): 662-70.
[http://dx.doi.org/10.2106/JBJS.I.01568] [PMID: 21471420]
[29]
Cheung KM. The relationship between disc degeneration, low back pain, and human pain genetics. Spine J 2010; 10(11): 958-60.
[http://dx.doi.org/10.1016/j.spinee.2010.09.011] [PMID: 20970736]
[30]
Roberts S, Caterson B, Menage J, Evans EH, Jaffray DC, Eisenstein SM. Matrix metalloproteinases and aggrecanase: Their role in disorders of the human intervertebral disc. Spine 2000; 25(23): 3005-13.
[http://dx.doi.org/10.1097/00007632-200012010-00007] [PMID: 11145811]
[31]
Vo NV, Hartman RA, Yurube T, Jacobs LJ, Sowa GA, Kang JD. Expression and regulation of metalloproteinases and their inhibitors in intervertebral disc aging and degeneration. Spine J 2013; 13(3): 331-41.
[http://dx.doi.org/10.1016/j.spinee.2012.02.027] [PMID: 23369495]
[32]
Buckwalter JA. Aging and degeneration of the human intervertebral disc. Spine 1995; 20(11): 1307-14.
[http://dx.doi.org/10.1097/00007632-199506000-00022] [PMID: 7660243]
[33]
Huang YC, Urban JP, Luk KD. Intervertebral disc regeneration: Do nutrients lead the way? Nat Rev Rheumatol 2014; 10(9): 561-6.
[http://dx.doi.org/10.1038/nrrheum.2014.91] [PMID: 24914695]
[34]
Cazzanelli P, Wuertz-Kozak K. MicroRNAs in intervertebral disc degeneration, apoptosis, inflammation, and mechanobiology. Int J Mol Sci 2020; 21(10): 3601.
[http://dx.doi.org/10.3390/ijms21103601] [PMID: 32443722]
[35]
Xia C, Zeng Z, Fang B, et al. Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects. Free Radic Biol Med 2019; 143: 1-15.
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.07.026] [PMID: 31351174]
[36]
Urban JP, Roberts S. Degeneration of the intervertebral disc. Arthritis Res Ther 2003; 5(3): 120-30.
[http://dx.doi.org/10.1186/ar629] [PMID: 12723977]
[37]
Zhao K, An R, Xiang Q, et al. Acid-sensing ion channels regulate nucleus pulposus cell inflammation and pyroptosis via the NLRP3 inflammasome in intervertebral disc degeneration. Cell Prolif 2021; 54(1): e12941.
[http://dx.doi.org/10.1111/cpr.12941] [PMID: 33111436]
[38]
Song Y, Wang Y, Zhang Y, et al. Advanced glycation end products regulate anabolic and catabolic activities via NLRP3-inflammasome activation in human nucleus pulposus cells. J Cell Mol Med 2017; 21(7): 1373-87.
[http://dx.doi.org/10.1111/jcmm.13067] [PMID: 28224704]
[39]
Wang J, Nisar M, Huang C, et al. Small molecule natural compound agonist of SIRT3 as a therapeutic target for the treatment of intervertebral disc degeneration. Exp Mol Med 2018; 50(11): 1-14.
[http://dx.doi.org/10.1038/s12276-018-0173-3] [PMID: 30420619]
[40]
Sudo H, Minami A. Regulation of apoptosis in nucleus pulposus cells by optimized exogenous Bcl-2 overexpression. J Orthop Res 2010; 28(12): 1608-13.
[http://dx.doi.org/10.1002/jor.21185] [PMID: 20589931]
[41]
Risbud MV, Shapiro IM. Role of cytokines in intervertebral disc degeneration: Pain and disc content. Nat Rev Rheumatol 2014; 10(1): 44-56.
[http://dx.doi.org/10.1038/nrrheum.2013.160] [PMID: 24166242]
[42]
Butler WF. Comparative anatomy and development of the mammalian disc The Biology of the Intervertebral Disc 1988.
[43]
Ohshima H, Urban J. Effect of lactate concentrations and pH on matrix synthesis rates in the intervertebral disc. Spine 1992; 17: 1079-82.
[http://dx.doi.org/10.1097/00007632-199209000-00012] [PMID: 1411761]
[44]
Ishihara H, Urban JP. Effects of low oxygen concentrations and metabolic inhibitors on proteoglycan and protein synthesis rates in the intervertebral disc. J Orthop Res 1999; 17(6): 829-35.
[http://dx.doi.org/10.1002/jor.1100170607] [PMID: 10632449]
[45]
Horner HA, Urban JP. 2001 volvo award winner in basic science studies: Effect of nutrient supply on the viability of cells from the nucleus pulposus of the intervertebral disc. Spine 2001; 26(23): 2543-9.
[http://dx.doi.org/10.1097/00007632-200112010-00006] [PMID: 11725234]
[46]
Kauppila LI, McAlindon T, Evans S, Wilson PW, Kiel D, Felson DT. Disc degeneration/back pain and calcification of the abdominal aorta. A 25-year follow-up study in Framingham. Spine 1997; 22(14): 1642-7.
[http://dx.doi.org/10.1097/00007632-199707150-00023] [PMID: 9253101]
[47]
Kauppila LI. Prevalence of stenotic changes in arteries supplying the lumbar spine. A postmortem angiographic study on 140 subjects. Ann Rheum Dis 1997; 56(10): 591-5.
[http://dx.doi.org/10.1136/ard.56.10.591] [PMID: 9389219]
[48]
Jones J. Subchondral osteonecrosis can conceivably cause disk degeneration and” primary” osteoarthritis. Osteonecrosis 1997.
[49]
Holm S, Nachemson A. Variations in the nutrition of the canine intervertebral disc induced by motion. Spine 1983; 8(8): 866-74.
[http://dx.doi.org/10.1097/00007632-198311000-00009] [PMID: 6670021]
[50]
Holm S, Nachemson A. Nutritional changes in the canine intervertebral disc after spinal fusion. Clin Orthop Relat Res 1982; (169): 243-58.
[http://dx.doi.org/10.1097/00003086-198209000-00036] [PMID: 7105584]
[51]
Allan DB, Waddell G. An historical perspective on low back pain and disability. Acta Orthopaedica Scandinavica 1989; 60: 1-23.
[http://dx.doi.org/10.3109/17453678909153916]
[52]
Puustjärvi K, Lammi M, Helminen H, Inkinen R, Tammi M. Proteoglycans in the intervertebral disc of young dogs following strenuous running exercise. Connect Tissue Res 1994; 30(3): 225-40.
[http://dx.doi.org/10.3109/03008209409061974] [PMID: 8039389]
[53]
Iatridis JC, Mente PL, Stokes IA, Aronsson DD, Alini M. Compression-induced changes in intervertebral disc properties in a rat tail model. Spine 1999; 24(10): 996-1002.
[http://dx.doi.org/10.1097/00007632-199905150-00013] [PMID: 10332792]
[54]
Lotz JC, Colliou OK, Chin JR, Duncan NA, Liebenberg E. Compression-induced degeneration of the intervertebral disc: An in vivo mouse model and finite-element study. Spine 1998; 23(23): 2493-506.
[http://dx.doi.org/10.1097/00007632-199812010-00004] [PMID: 9854748]
[55]
Jay Lipson S, Muir H. Experimental intervertebral disc degeneration. Morphologic and proteoglycan changes over time. Arthritis & Rheumatism. Official J of the American College of Rheumatology 1981; 24(1): 12-21.
[56]
Pope MH, Goh KL, Magnusson ML. Spine ergonomics. Annu Rev Biomed Eng 2002; 4(1): 49-68.
[http://dx.doi.org/10.1146/annurev.bioeng.4.092101.122107] [PMID: 12117750]
[57]
Heliövaara M. Risk factors for low back pain and sciatica. Ann Med 1989; 21(4): 257-64.
[http://dx.doi.org/10.3109/07853898909149202] [PMID: 2528971]
[58]
Mohanty S, Dahia CL. Defects in intervertebral disc and spine during development, degeneration, and pain: New research directions for disc regeneration and therapy. Wiley Interdiscip Rev Dev Biol 2019; 8(4): e343.
[http://dx.doi.org/10.1002/wdev.343] [PMID: 30977275]
[59]
Heikkilä JK, Koskenvuo M, Heliövaara M, et al. Genetic and environmental factors in sciatica. Evidence from a nationwide panel of 9365 adult twin pairs. Ann Med 1989; 21(5): 393-8.
[http://dx.doi.org/10.3109/07853898909149227] [PMID: 2605032]
[60]
Matsui H, Kanamori M, Ishihara H, Yudoh K, Naruse Y, Tsuji H. Familial predisposition for lumbar degenerative disc disease. A case-control study. Spine 1998; 23(9): 1029-34.
[http://dx.doi.org/10.1097/00007632-199805010-00013] [PMID: 9589542]
[61]
Varlotta GP, Brown MD, Kelsey JL, Golden AL. Familial predisposition for herniation of a lumbar disc in patients who are less than twenty-one years old. J Bone Joint Surg Am 1991; 73(1): 124-8.
[http://dx.doi.org/10.2106/00004623-199173010-00016] [PMID: 1824705]
[62]
Battié MC, Videman T, Gibbons LE, Fisher LD, Manninen H, Gill K. 1995 Volvo Award in clinical sciences. Determinants of lumbar disc degeneration. A study relating lifetime exposures and magnetic resonance imaging findings in identical twins. Spine 1995; 20(24): 2601-12.
[http://dx.doi.org/10.1097/00007632-199512150-00001] [PMID: 8747238]
[63]
Sambrook PN, MacGregor AJ, Spector TD. Genetic influences on cervical and lumbar disc degeneration: A magnetic resonance imaging study in twins. Arthritis Rheum 1999; 42(2): 366-72.
[http://dx.doi.org/10.1002/1529-0131(199902)42:2<366:AID-ANR20>3.0.CO;2-6] [PMID: 10025932]
[64]
Battié MC, Haynor DR, Fisher LD, Gill K, Gibbons LE, Videman T. Similarities in degenerative findings on magnetic resonance images of the lumbar spines of identical twins. J Bone Joint Surg Am 1995; 77(11): 1662-70.
[http://dx.doi.org/10.2106/00004623-199511000-00004] [PMID: 7593075]
[65]
Ala-Kokko L. Genetic risk factors for lumbar disc disease. Ann Med 2002; 34(1): 42-7.
[http://dx.doi.org/10.1080/078538902317338634] [PMID: 12014433]
[66]
Annunen S, Paassilta P, Lohiniva J, et al. An allele of COL9A2 associated with intervertebral disc disease. Science 1999; 285(5426): 409-12.
[http://dx.doi.org/10.1126/science.285.5426.409] [PMID: 10411504]
[67]
Paassilta P, Lohiniva J, Göring HH, et al. Identification of a novel common genetic risk factor for lumbar disk disease. JAMA 2001; 285(14): 1843-9.
[http://dx.doi.org/10.1001/jama.285.14.1843] [PMID: 11308397]
[68]
Kawaguchi Y, Osada R, Kanamori M, et al. Association between an aggrecan gene polymorphism and lumbar disc degeneration. Spine 1999; 24(23): 2456-60.
[http://dx.doi.org/10.1097/00007632-199912010-00006] [PMID: 10626307]
[69]
Watanabe H, Nakata K, Kimata K, Nakanishi I, Yamada Y. Dwarfism and age-associated spinal degeneration of heterozygote cmd mice defective in aggrecan. Proc Natl Acad Sci USA 1997; 94(13): 6943-7.
[http://dx.doi.org/10.1073/pnas.94.13.6943] [PMID: 9192671]
[70]
Li S-W, Prockop DJ, Helminen H, et al. Transgenic mice with targeted inactivation of the Col2 alpha 1 gene for collagen II develop a skeleton with membranous and periosteal bone but no endochondral bone. Genes Dev 1995; 9(22): 2821-30.
[http://dx.doi.org/10.1101/gad.9.22.2821] [PMID: 7590256]
[71]
Kimura T, Nakata K, Tsumaki N, et al. Progressive degeneration of articular cartilage and intervertebral discs. An experimental study in transgenic mice bearing a type IX collagen mutation. Int Orthop 1996; 20(3): 177-81.
[http://dx.doi.org/10.1007/s002640050058] [PMID: 8832322]
[72]
Superti-Furga A, Bonafé L, Rimoin DL. Molecular-pathogenetic classification of genetic disorders of the skeleton. Am J Med Genet 2001; 106(4): 282-93.
[http://dx.doi.org/10.1002/ajmg.10233] [PMID: 11891680]
[73]
Lee YC, Zotti MGT, Osti OL. Operative management of lumbar degenerative disc disease. Asian Spine J 2016; 10(4): 801-19.
[http://dx.doi.org/10.4184/asj.2016.10.4.801] [PMID: 27559465]
[74]
Clouet J, Vinatier C, Merceron C, et al. The intervertebral disc: From pathophysiology to tissue engineering. Joint Bone Spine 2009; 76(6): 614-8.
[http://dx.doi.org/10.1016/j.jbspin.2009.07.002] [PMID: 19819178]
[75]
Gruber HE, Norton HJ, Hanley EN Jr. Anti-apoptotic effects of IGF-1 and PDGF on human intervertebral disc cells in vitro. Spine 2000; 25(17): 2153-7.
[http://dx.doi.org/10.1097/00007632-200009010-00002] [PMID: 10973395]
[76]
Thompson JP, Oegema TR Jr, Bradford DS. Stimulation of mature canine intervertebral disc by growth factors. Spine 1991; 16(3): 253-60.
[http://dx.doi.org/10.1097/00007632-199103000-00001] [PMID: 2028297]
[77]
Li J, Yoon ST, Hutton WC. Effect of bone morphogenetic protein-2 (BMP-2) on matrix production, other BMPs, and BMP receptors in rat intervertebral disc cells. J Spinal Disord Tech 2004; 17(5): 423-8.
[http://dx.doi.org/10.1097/01.bsd.0000112084.85112.5d] [PMID: 15385883]
[78]
Sawamura K, Ikeda T, Nagae M, et al. Characterization of in vivo effects of platelet-rich plasma and biodegradable gelatin hydrogel microspheres on degenerated intervertebral discs. Tissue Eng Part A 2009; 15(12): 3719-27.
[http://dx.doi.org/10.1089/ten.tea.2008.0697] [PMID: 19514846]
[79]
Harrison P, Cramer EM. Platelet alpha-granules. Blood Rev 1993; 7(1): 52-62.
[http://dx.doi.org/10.1016/0268-960X(93)90024-X] [PMID: 8467233]
[80]
Tuakli-Wosornu YA, Terry A, Boachie-Adjei K, et al. Lumbar intradiskal platelet-rich plasma (PRP) injections: A prospective, double-blind, randomized controlled study. PM R 2016; 8(1): 1-10.
[http://dx.doi.org/10.1016/j.pmrj.2015.08.010] [PMID: 26314234]
[81]
Ross R. Platelet-derived growth factor. Annu Rev Med 1987; 38: 71-9.
[http://dx.doi.org/10.1146/annurev.me.38.020187.000443] [PMID: 3555311]
[82]
Carter CA, Jolly DG, Worden CE Sr, Hendren DG, Kane CJ. Platelet-rich plasma gel promotes differentiation and regeneration during equine wound healing. Exp Mol Pathol 2003; 74(3): 244-55.
[http://dx.doi.org/10.1016/S0014-4800(03)00017-0] [PMID: 12782011]
[83]
Monfett M, Harrison J, Boachie-Adjei K, Lutz G. Intradiscal platelet-rich plasma (PRP) injections for discogenic low back pain: An update. Int Orthop 2016; 40(6): 1321-8.
[http://dx.doi.org/10.1007/s00264-016-3178-3] [PMID: 27073034]
[84]
Gullung GB, Woodall JW, Tucci MA, James J, Black DA, McGuire RA. Platelet-rich plasma effects on degenerative disc disease: Analysis of histology and imaging in an animal model. Evid Based Spine Care J 2011; 2(4): 13-8.
[http://dx.doi.org/10.1055/s-0031-1274752] [PMID: 23230401]
[85]
Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 2010; 11(9): 597-610.
[http://dx.doi.org/10.1038/nrg2843] [PMID: 20661255]
[86]
Smith LJ, Silverman L, Sakai D, et al. Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: Recommendations of the ORS spine section. JOR Spine 2018; 1(4): e1036.
[http://dx.doi.org/10.1002/jsp2.1036] [PMID: 30895277]
[87]
Hohaus C, Ganey TM, Minkus Y, Meisel HJ. Cell transplantation in lumbar spine disc degeneration disease. Eur Spine J 2008; 17(4) (Suppl. 4): 492-503.
[http://dx.doi.org/10.1007/s00586-008-0750-6] [PMID: 19005697]
[88]
Meisel HJ, Siodla V, Ganey T, Minkus Y, Hutton WC, Alasevic OJ. Clinical experience in cell-based therapeutics: Disc chondrocyte transplantation A treatment for degenerated or damaged intervertebral disc. Biomol Eng 2007; 24(1): 5-21.
[http://dx.doi.org/10.1016/j.bioeng.2006.07.002] [PMID: 16963315]
[89]
Hegewald AA, Endres M, Abbushi A, et al. Adequacy of herniated disc tissue as a cell source for nucleus pulposus regeneration. J Neurosurg Spine 2011; 14(2): 273-80.
[http://dx.doi.org/10.3171/2010.10.SPINE10223] [PMID: 21214312]
[90]
Silverman LI, Dulatova G, Tandeski T, et al. In vitro and in vivo evaluation of discogenic cells, an investigational cell therapy for disc degeneration. Spine J 2020; 20(1): 138-49.
[http://dx.doi.org/10.1016/j.spinee.2019.08.006] [PMID: 31442616]
[91]
Chen J, Lee EJ, Jing L, Christoforou N, Leong KW, Setton LA. Differentiation of mouse induced pluripotent stem cells (iPSCs) into nucleus pulposus-like cells in vitro. PLoS One 2013; 8(9): e75548.
[http://dx.doi.org/10.1371/journal.pone.0075548] [PMID: 24086564]
[92]
Urban JP, Holm S, Maroudas A, Nachemson A. Nutrition of the intervertebral disk. An in vivo study of solute transport. Clin Orthop Relat Res 1977; (129): 101-14.
[http://dx.doi.org/10.1097/00003086-197711000-00012] [PMID: 608268]
[93]
Blanco JF, Villarón EM, Pescador D, et al. Autologous mesenchymal stromal cells embedded in tricalcium phosphate for posterolateral spinal fusion: Results of a prospective phase I/II clinical trial with long-term follow-up. Stem Cell Res Ther 2019; 10(1): 63.
[http://dx.doi.org/10.1186/s13287-019-1166-4] [PMID: 30795797]
[94]
Guyer RD, McAfee PC, Banco RJ, et al. Prospective, randomized, multicenter Food and Drug Administration investigational device exemption study of lumbar total disc replacement with the CHARITE artificial disc versus lumbar fusion: Five-year follow-up. Spine J 2009; 9(5): 374-86.
[http://dx.doi.org/10.1016/j.spinee.2008.08.007] [PMID: 18805066]
[95]
Le Blanc K, Ringdén O. Mesenchymal stem cells: Properties and role in clinical bone marrow transplantation. Curr Opin Immunol 2006; 18(5): 586-91.
[http://dx.doi.org/10.1016/j.coi.2006.07.004] [PMID: 16879957]
[96]
Kumar H, Ha D-H, Lee E-J, et al. Safety and tolerability of intradiscal implantation of combined autologous adipose-derived mesenchymal stem cells and hyaluronic acid in patients with chronic discogenic low back pain: 1-year follow-up of a phase I study. Stem Cell Res Ther 2017; 8(1): 262.
[http://dx.doi.org/10.1186/s13287-017-0710-3] [PMID: 29141662]
[97]
Hwang NS, Zhang C, Hwang YS, Varghese S. Mesenchymal stem cell differentiation and roles in regenerative medicine. Wiley Interdiscip Rev Syst Biol Med 2009; 1(1): 97-106.
[http://dx.doi.org/10.1002/wsbm.26] [PMID: 20835984]
[98]
Hingert D, Nawilaijaroen P, Aldridge J, Baranto A, Brisby H. Investigation of the effect of secreted factors from mesenchymal stem cells on disc cells from degenerated discs. Cells Tissues Organs 2019; 208(1-2): 76-88.
[http://dx.doi.org/10.1159/000506350] [PMID: 32092752]
[99]
Xie B, Chen S, Xu Y, et al. Clinical efficacy and safety of human mesenchymal stem cell therapy for degenerative disc disease: A systematic review and meta-analysis of randomized controlled trials. Stem Cells Int 2021; 2021: 9149315.
[http://dx.doi.org/10.1155/2021/9149315] [PMID: 34557231]
[100]
Vadalà G, Ambrosio L, Russo F, Papalia R, Denaro V. Stem cells and intervertebral disc regeneration overview-what they can and can’t do. Int J Spine Surg 2021; 15(s1): 40-53.
[http://dx.doi.org/10.14444/8054] [PMID: 34376495]
[101]
Chen S, Zhao L, Deng X, et al. Mesenchymal stem cells protect nucleus pulposus cells from compression-induced apoptosis by inhibiting the mitochondrial pathway. Stem Cells Int 2017; 2017: 9843120.
[http://dx.doi.org/10.1155/2017/9843120] [PMID: 29387092]
[102]
Elabd C, Ichim TE, Miller K, et al. Comparing atmospheric and hypoxic cultured mesenchymal stem cell transcriptome: Implication for stem cell therapies targeting intervertebral discs. J Transl Med 2018; 16(1): 222.
[http://dx.doi.org/10.1186/s12967-018-1601-9] [PMID: 30097061]
[103]
Yoshikawa T, Ueda Y, Miyazaki K, Koizumi M, Takakura Y. Disc regeneration therapy using marrow mesenchymal cell transplantation: A report of two case studies. Spine 2010; 35(11): E475-80.
[http://dx.doi.org/10.1097/BRS.0b013e3181cd2cf4] [PMID: 20421856]
[104]
Orozco L, Soler R, Morera C, Alberca M, Sánchez A, García-Sancho J. Intervertebral disc repair by autologous mesenchymal bone marrow cells: A pilot study. Transplantation 2011; 92(7): 822-8.
[http://dx.doi.org/10.1097/TP.0b013e3182298a15] [PMID: 21792091]
[105]
Elabd C, Centeno CJ, Schultz JR, Lutz G, Ichim T, Silva FJ. Intra-discal injection of autologous, hypoxic cultured bone marrow-derived mesenchymal stem cells in five patients with chronic lower back pain: A long-term safety and feasibility study. J Transl Med 2016; 14(1): 253.
[http://dx.doi.org/10.1186/s12967-016-1015-5] [PMID: 27585696]
[106]
Henriksson HB, Papadimitriou N, Hingert D, Baranto A, Lindahl A, Brisby H. The traceability of mesenchymal stromal cells after injection into degenerated discs in patients with low back pain. Stem Cells Dev 2019; 28(17): 1203-11.
[http://dx.doi.org/10.1089/scd.2019.0074] [PMID: 31237488]
[107]
Centeno C, Markle J, Dodson E, et al. Treatment of lumbar degenerative disc disease-associated radicular pain with culture-expanded autologous mesenchymal stem cells: A pilot study on safety and efficacy. J Transl Med 2017; 15(1): 197.
[http://dx.doi.org/10.1186/s12967-017-1300-y] [PMID: 28938891]
[108]
Wang P, Li Y, Huang L, et al. Effects and safety of allogenic mesenchymal stem cell intravenous infusion in active ankylosing spondylitis patients who failed NSAIDs: A 20-week clinical trial. Cell Transplant 2014; 23(10): 1293-303.
[http://dx.doi.org/10.3727/096368913X667727] [PMID: 23711393]
[109]
Noriega DC, Ardura F, Hernández-Ramajo R, et al. Intervertebral disc repair by allogeneic mesenchymal bone marrow cells: A randomized controlled trial. Transplantation 2017; 101(8): 1945-51.
[http://dx.doi.org/10.1097/TP.0000000000001484] [PMID: 27661661]
[110]
Amirdelfan K, Bae H, McJunkin T, et al. Allogeneic mesenchymal precursor cells treatment for chronic low back pain associated with degenerative disc disease: A prospective randomized, placebo-controlled 36-month study of safety and efficacy. Spine J 2021; 21(2): 212-30.
[http://dx.doi.org/10.1016/j.spinee.2020.10.004] [PMID: 33045417]
[111]
Pang X, Yang H, Peng B. Human umbilical cord mesenchymal stem cell transplantation for the treatment of chronic discogenic low back pain. Pain Physician 2014; 17(4): E525-30.
[http://dx.doi.org/10.36076/ppj.2014/17/E525] [PMID: 25054402]
[112]
Haufe SM, Mork AR. Intradiscal injection of hematopoietic stem cells in an attempt to rejuvenate the intervertebral discs. Stem Cells Dev 2006; 15(1): 136-7.
[http://dx.doi.org/10.1089/scd.2006.15.136] [PMID: 16522171]
[113]
Chun H-J, Kim YS, Kim BK, et al. Transplantation of human adipose-derived stem cells in a rabbit model of traumatic degeneration of lumbar discs. World Neurosurg 2012; 78(3-4): 364-71.
[http://dx.doi.org/10.1016/j.wneu.2011.12.084] [PMID: 22381275]
[114]
Marfia G, Campanella R, Navone SE, et al. Potential use of human adipose mesenchymal stromal cells for intervertebral disc regeneration: A preliminary study on biglycan-deficient murine model of chronic disc degeneration. Arthritis Res Ther 2014; 16(5): 457.
[http://dx.doi.org/10.1186/s13075-014-0457-5] [PMID: 25293819]
[115]
Comella K, Silbert R, Parlo M. Effects of the intradiscal implantation of stromal vascular fraction plus platelet rich plasma in patients with degenerative disc disease. J Transl Med 2017; 15(1): 1-8.
[PMID: 28049494]
[116]
Piccirilli M, Delfinis CP, Santoro A, Salvati M. Mesenchymal stem cells in lumbar spine surgery: A single institution experience about red bone marrow and fat tissue derived MSCs. J Neurosurg Sci 2017; 61(2): 124-33.
[PMID: 26082381]
[117]
Pettine KA, Murphy MB, Suzuki RK, Sand TT. Percutaneous injection of autologous bone marrow concentrate cells significantly reduces lumbar discogenic pain through 12 months. Stem Cells 2015; 33(1): 146-56.
[http://dx.doi.org/10.1002/stem.1845] [PMID: 25187512]
[118]
Subach BR, Copay AG, Martin MM, Schuler TC, DeWolfe DS. Epidural abscess and cauda equina syndrome after percutaneous intradiscal therapy in degenerative lumbar disc disease. Spine J 2012; 12(11): e1-4.
[http://dx.doi.org/10.1016/j.spinee.2012.10.004] [PMID: 23131581]
[119]
Kasamkattil J, Gryadunova A, Martin I, et al. Spheroid-based tissue engineering strategies for regeneration of the intervertebral disc. Int J Mol Sci 2022; 23(5): 2530.
[http://dx.doi.org/10.3390/ijms23052530] [PMID: 35269672]
[120]
Williams RJ, Tryfonidou MA, Snuggs JW, Le Maitre CL. Cell sources proposed for nucleus pulposus regeneration. JOR Spine 2021; 4(4): e1175.
[http://dx.doi.org/10.1002/jsp2.1175] [PMID: 35005441]
[121]
Shu CC, Dart A, Bell R, et al. Efficacy of administered mesenchymal stem cells in the initiation and co-ordination of repair processes by resident disc cells in an ovine (Ovis aries) large destabilizing lesion model of experimental disc degeneration. JOR Spine 2018; 1(4): e1037.
[http://dx.doi.org/10.1002/jsp2.1037] [PMID: 31463452]
[122]
Blanquer SBG, Grijpma DW, Poot AA. Delivery systems for the treatment of degenerated intervertebral discs. Adv Drug Deliv Rev 2015; 84: 172-87.
[http://dx.doi.org/10.1016/j.addr.2014.10.024] [PMID: 25451138]
[123]
Clouet J, Fusellier M, Camus A, Le Visage C, Guicheux J. Intervertebral disc regeneration: From cell therapy to the development of novel bioinspired endogenous repair strategies. Adv Drug Deliv Rev 2019; 146: 306-24.
[http://dx.doi.org/10.1016/j.addr.2018.04.017] [PMID: 29705378]
[124]
Guiot BH, Fessler RG. Molecular biology of degenerative disc disease. Neurosurgery 2000; 47(5): 1034-40.
[http://dx.doi.org/10.1097/00006123-200011000-00003] [PMID: 11063096]
[125]
Cowell HR, Hall JN, MacEwen GD. Genetic aspects of idiopathic scoliosis. A Nicholas Andry Award essay, 1970. Clin Orthop Relat Res 1972; 86(86): 121-31.
[http://dx.doi.org/10.1097/00003086-197207000-00018] [PMID: 5047777]
[126]
Emery AE, Lawrence JS. Genetics of ankylosing spondylitis. J Med Genet 1967; 4(4): 239-44.
[http://dx.doi.org/10.1136/jmg.4.4.239] [PMID: 6082899]
[127]
Schlosstein L, Terasaki PI, Bluestone R, Pearson CM. High association of an HL-A antigen, W27, with ankylosing spondylitis. N Engl J Med 1973; 288(14): 704-6.
[http://dx.doi.org/10.1056/NEJM197304052881403] [PMID: 4688372]
[128]
Sobajima S, Vadala G, Shimer A, Kim JS, Gilbertson LG, Kang JD. Feasibility of a stem cell therapy for intervertebral disc degeneration. Spine J 2008; 8(6): 888-96.
[http://dx.doi.org/10.1016/j.spinee.2007.09.011] [PMID: 18082460]
[129]
Binch ALA, Fitzgerald JC, Growney EA, Barry F. Cell-based strategies for IVD repair: Clinical progress and translational obstacles. Nat Rev Rheumatol 2021; 17(3): 158-75.
[http://dx.doi.org/10.1038/s41584-020-00568-w] [PMID: 33526926]
[130]
McDonnell EE, Buckley CT. Consolidating and re-evaluating the human disc nutrient microenvironment. JOR SPINE 5(1)
[http://dx.doi.org/10.1002/jsp2.1192]
[131]
Wuertz K, Godburn K, Neidlinger-Wilke C, Urban J, Iatridis JC. Behavior of mesenchymal stem cells in the chemical microenvironment of the intervertebral disc. Spine 2008; 33(17): 1843-9.
[http://dx.doi.org/10.1097/BRS.0b013e31817b8f53] [PMID: 18670337]
[132]
Vadalà G, Sowa G, Hubert M, Gilbertson LG, Denaro V, Kang JD. Mesenchymal stem cells injection in degenerated intervertebral disc: Cell leakage may induce osteophyte formation. J Tissue Eng Regen Med 2012; 6(5): 348-55.
[http://dx.doi.org/10.1002/term.433] [PMID: 21671407]
[133]
Vadalà G, Russo F, Musumeci M, Valentini A, Bernardini M, Denaro L, et al. Disc regeneration using MSC transplanted via the endplate route. Global Spine Journal 2016; 6: s-0036-s-1582614.
[http://dx.doi.org/10.1055/s-0036-1582614]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy