Low-dose Mesenchymal Stem Cell Therapy for Discogenic Pain: Safety and Efficacy Results From a 1-year Feasibility Study

References

• DeyoRA , RainvilleJ , KentDL. What can the history and physical examination tell us about low back pain?JAMA268(6), 760–765 (1992).
   PubMed Web of Science ®Google Scholar
• KinkadeS. Evaluation and treatment of acute low back pain. Am. Fam. Physician75(8), 1181–1188 (2007).
   PubMed Web of Science ®Google Scholar
• WalkerBF , MullerR , GrantWD. Low back pain in Australian adults. Prevalence and associated disability. J. Manipulative Physiol. Ther.27(4), 238–244 (2004).
   PubMed Web of Science ®Google Scholar
• WaddellG , NewtonM , HendersonI , SomervilleD , MainCJ. A Fear-Avoidance Beliefs Questionnaire (FABQ) and the role of fear-avoidance beliefs in chronic low back pain and disability. Pain52(2), 157–168 (1993).
   PubMed Web of Science ®Google Scholar
• EngersAJ , JellemaP , WensingM , vander Windt DA , GrolR , van TulderMW. Individual patient education for low back pain. Cochrane Database Syst. Rev.2008(1), CD004057 (2008).
   PubMedGoogle Scholar
• ManiadakisN , GrayA. The economic burden of back pain in the UK. Pain84(1), 95–103 (2000).
   PubMed Web of Science ®Google Scholar
• van TulderMW , KoesBW , BouterLM. A cost-of-illness study of back pain in The Netherlands. Pain62(2), 233–240 (1995).
   PubMed Web of Science ®Google Scholar
• StevensonC , Al-YamanF , GrauJet al.Australian Institute of Health and Welfare 2000. Australia's Health 2000: the seventh biennial report of the Australian Institute of Health and Welfare. Canberra: AIHW. 97–100 (2000).
   Google Scholar
• Von KorffM , DeyoRA , CherkinD , BarlowW. Back pain in primary care. Outcomes at 1 year. Spine18(7), 855–862 (1993).
   PubMed Web of Science ®Google Scholar
• SchwarzerAC , AprillCN , DerbyR , FortinJ , KineG , BogdukN. The prevalence and clinical features of internal disc disruption in patients with chronic low back pain. Spine20(17), 1878–1883 (1995).
   PubMed Web of Science ®Google Scholar
• PengB , FuX , PangXet al.Prospective clinical study on natural history of discogenic low back pain at 4 years of follow-up. Pain Physician15(6), 525–532 (2012).
   PubMed Web of Science ®Google Scholar
• AdamsM , McNallyD , WagstaffJ , GoodshipA. Abnormal stress concentrations in lumbar intervertebral discs following damage to the vertebral bodies: a cause of disc failure?Eur. Spine J.1(4), 214–221 (1993).
   PubMedGoogle Scholar
• HanssonT , KellerT , SpenglerD. Mechanical behavior of the human lumbar spine. II. Fatigue strength during dynamic compressive loading. J. Orthop. Res.5(4), 479–487 (1987).
   PubMed Web of Science ®Google Scholar
• LiuYK , NjusG , BuckwalterJ , WakanoK. Fatigue response of lumbar intervertebral joints under axial cyclic loading. Spine8(8), 857–865 (1983).
   PubMed Web of Science ®Google Scholar
• HolmS , HolmAK , EkströmL , KarladaniA , HanssonT. Experimental disc degeneration due to endplate injury. J. Spinal Disord. Tech.17(1), 64–71 (2004).
   PubMedGoogle Scholar
• JarrayaM , GuermaziA , LorbergsALet al.A longitudinal study of disc height narrowing and facet joint osteoarthritis at the thoracic and lumbar spine, evaluated by computed tomography: the Framingham Study. Spine J.18(11), 2065–2073 (2018).
   PubMed Web of Science ®Google Scholar
• SiemionowK , AnH , MasudaK , AnderssonG , Cs-SzaboG. The Effects of age, gender, ethnicity, and spinal level on the rate of intervertebral disc degeneration. A review of 1712 intervertebral discs. Spine36(17), 1333 (2011).
   PubMed Web of Science ®Google Scholar
• VidemanT , BattiéMC , ParentE , GibbonsLE , VainioP , KaprioJ. Progression and determinants of quantitative magnetic resonance imaging measures of lumbar disc degeneration: a five-year follow-up of adult male monozygotic twins. Spine33(13), 1484–1490 (2008).
   PubMed Web of Science ®Google Scholar
• TeraguchiM , YoshimuraN , HashizumeHet al.Progression, incidence, and risk factors for intervertebral disc degeneration in a longitudinal population-based cohort: the Wakayama Spine Study. Osteoarthritis Cartilage25(7), 1122–1131 (2017).
   PubMed Web of Science ®Google Scholar
• HassettG , HartD , ManekN , DoyleD , SpectorT. Risk factors for progression of lumbar spine disc degeneration: the Chingford Study. Arthritis Rheum.48(11), 3112–3117 (2003).
   PubMedGoogle Scholar
• García-CosamalónJ , DelValle ME , CalaviaMGet al.Intervertebral disc, sensory nerves and neurotrophins: who is who in discogenic pain?J. Anat.217(1), 1–15 (2010).
   PubMed Web of Science ®Google Scholar
• BogdukN. Practice guidelines for spinal diagnostic and treatment procedures.International Spine Intervention Society, (2013).
   Google Scholar
• LennardTA , VivianDG , WalkowskiSD , SinglaAK. Pain Procedures in Clinical Practice E-Book.Elsevier Health Sciences, (2011).
   Google Scholar
• CarrageeEJ , LincolnT , ParmarVS , AlaminT. A gold standard evaluation of the “discogenic pain” diagnosis as determined by provocative discography. Spine31(18), 2115–2123 (2006).
   PubMed Web of Science ®Google Scholar
• LongoUG , PapapietroN , PetrilloS , FranceschettiE , MaffulliN , DenaroV. Mesenchymal stem cell for prevention and management of intervertebral disc degeneration. Stem Cells Int.2012, 921053 (2012).
   PubMed Web of Science ®Google Scholar
• TaherF , EssigD , LeblDRet al.Lumbar degenerative disc disease: current and future concepts of diagnosis and management. Adv. Orthop.2012, 970752 (2012).
   PubMedGoogle Scholar
• BarryFP. Biology and clinical applications of mesenchymal stem cells. Birth Defects Res. C Embryo Today69(3), 250–256 (2003).
   PubMedGoogle Scholar
• ArinzehTL. Mesenchymal stem cells for bone repair: preclinical studies and potential orthopaedic applications. Foot Ankle Clin.10(4), 651–665 (2005).
   PubMedGoogle Scholar
• NoelD , DjouadF , JorgenseC. Regenerative medicine through mesenchymal stem cells for bone and cartilage repair. Curr. Opin. Investig. Drugs3(7), 1000–1004 (2002).
   PubMedGoogle Scholar
• CaplanAI , CorreaD. The MSC: an injury drugstore. Cell Stem Cell9(1), 11–15 (2011).
   PubMed Web of Science ®Google Scholar
• NakagamiH , MorishitaR , MaedaK , KikuchiY , OgiharaT , KanedaY. Adipose tissue-derived stromal cells as a novel option for regenerative cell therapy. J. Atheroscler. Thromb.13(2), 77–81 (2006).
   PubMed Web of Science ®Google Scholar
• WuL , LeijtenJC , GeorgiN , PostJN , van BlitterswijkCA , KarperienM. Trophic effects of mesenchymal stem cells increase chondrocyte proliferation and matrix formation. Tissue Eng.17(9–10), 1425–1436 (2011).
   Google Scholar
• SpeesJL , LeeRH , GregoryCA. Mechanisms of mesenchymal stem/stromal cell function. Stem Cell. Res. Ther.7(1), 1–13 (2016).
   PubMedGoogle Scholar
• DjouadF , BouffiC , GhannamS. Mesenchymal stem cell: innovative therapeutic tools for rheumatic diseases. Nat. Rev. Rheumatol.5, 392–399 (2009).
   PubMed Web of Science ®Google Scholar
• CaplanAI. Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J. Cell. Physiol.213, 341–347 (2007).
   PubMed Web of Science ®Google Scholar
• LeungVY , AladinDM , LvFet al.Mesenchymal stem cells reduce intervertebral disc fibrosis and facilitate repair. Stem Cells32(8), 2164–2177 (2014).
   PubMed Web of Science ®Google Scholar
• MeiselHJ , SiodlaV , GaneyT , MinkusY , HuttonWC , AlasevicOJ. Clinical experience in cell-based therapeutics: disc chondrocyte transplantation: a treatment for degenerated or damaged intervertebral disc. Biomol. Eng.24(1), 5–21 (2007).
   PubMedGoogle Scholar
• OrozcoL , SolerR , MoreraC , AlbercaM , SánchezA , García-SanchoJ. Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation92(7), 822–828 (2011).
   PubMed Web of Science ®Google Scholar
• YoshikawaT , UedaY , MiyazakiK , KoizumiM , TakakuraY. Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of two case studies. Spine35(11), E475–E480 (2010).
   PubMed Web of Science ®Google Scholar
• Mesoblast. Positive spinal disc repair trial results using Mesoblast adult stem cells. Global Newswire, (2014).
   Google Scholar
• WuT , SongHX , DongY , LiJH. Cell-based therapies for lumbar discogenic low back pain. Spine43(1), 49–57 (2018).
   PubMed Web of Science ®Google Scholar
• LaluMM , McIntyreL , PuglieseCet al.Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS ONE7(10), e47559 (2012).
   PubMed Web of Science ®Google Scholar
• PeetersCM , LeijsMJ. Safety of intra-articular cell-therapy with culture-expanded stem cells in humans: a systematic literature review. Osteo Cartilage21(10), 1465–1473 (2013).
   PubMed Web of Science ®Google Scholar
• PittengerMF , MackayAM , BeckSCet al.Multilineage potential of adult human mesenchymal stem cells. Science284(5411), 143–147 (1999).
   PubMed Web of Science ®Google Scholar
• DeUgarte DA. Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs174(3), 101–109 (2003).
   PubMed Web of Science ®Google Scholar
• KernS , EichlerJS , KluterH. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells24(5), 1294–1301 (2006).
   PubMed Web of Science ®Google Scholar
• ZukPA , ZhuM , MizunoHet al.Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng.7(2), 211–228 (2001).
   PubMedGoogle Scholar
• IzadpanahR , TryggC , PatelBet al.Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J. Cell. Biochem.99(5), 1285–1297 (2006).
   PubMed Web of Science ®Google Scholar
• KimJ , KangJW , ParkJHet al.Biological characterization of long-term cultured human mesenchymal stem cells. Arch. Pharm. Res.32(1), 117–126 (2009).
   PubMed Web of Science ®Google Scholar
• WangY , HanZ , SongY , HanZC. Safety of mesenchymal stem cells for clinical application. Stem Cells Int.2012, 652034 (2012).
   PubMed Web of Science ®Google Scholar
• RaJC , ShinIS , KimSHet al.Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem Cells Dev.20(8), 1297–1308 (2011).
   PubMed Web of Science ®Google Scholar
• KumarH , HaDH , LeeEJet 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.8(1), 1–14 (2017).
   PubMedGoogle Scholar
• FreitagJ , WickhamJ , ShahK , LiD , NorsworthyC , TenenA. Mesenchymal stem cell therapy combined with arthroscopic abrasion arthroplasty regenerates cartilage in patients with severe knee osteoarthritis: a case series. Regen. Med.15(8), 1957–1977 (2020).
   PubMed Web of Science ®Google Scholar
• MessinghamMJ , ArpeyCJ. Update on the use of antibiotics in cutaneous surgery. Dermatol. Surg.31, 1068–1078 (2005).
   PubMed Web of Science ®Google Scholar
• MartinelloT , BronziniI , MaccatrozzoLet al.Canine adipose-derived mesenchymal stem cells do not lose stem features after a long-term cryopreservation. Res. Vet. Sci.91(1), 18–24 (2011).
   PubMed Web of Science ®Google Scholar
• GohBC , ThirumalaS , KilroyG , DevireddyRV , GimbleJM. Cryopreservation characteristics of adipose-derived stem cells: maintenance of differentiation potential and viability. J. Tissue Eng. Regen. Med.1(4), 322–324 (2007).
   PubMed Web of Science ®Google Scholar
• DominiciM , BlancK , MuellerIet al.Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy8(4), 315–317 (2006).
   PubMed Web of Science ®Google Scholar
• KarciogluO , TopacogluH , DikmeO , DikmeO. A systematic review of the pain scales in adults: which to use?Am. J. Emerg. Med.36(4), 707–714 (2018).
   PubMed Web of Science ®Google Scholar
• DworkinRH , TurkDC , FarrarJTet al.Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain113(1–2), 9–19 (2005).
   PubMed Web of Science ®Google Scholar
• GuyW. ECDEU assessment manual for psychopharmacology.US Department of Health, Education, and Welfare, Public Health Service, (1976).
   Google Scholar
• SalaffiF , StancatiA , SilvestriCA , CiapettiA , GrassiW. Minimal clinically important changes in chronic musculoskeletal pain intensity measured on a numerical rating scale. Eur. J. Pain8(4), 283–291 (2004).
   PubMed Web of Science ®Google Scholar
• FarrarJT , YoungJPJr , LaMoreauxL , WerthJL , PooleRM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain94(2), 149–158 (2001).
   PubMed Web of Science ®Google Scholar
• LovibondSH , LovibondPF. Manual for the depression anxiety stress scales.Psychology Foundation of Australia, Sydney (1995).
   Google Scholar
• FairbankJC , PynsentPB. The Oswestry disability index. Spine25(22), 2940–2953 (2000).
   PubMed Web of Science ®Google Scholar
• FairbankJ , CouperJ , DaviesJ , O'BrienJ. The Oswestry low back pain disability questionnaire. Physiotherapy66(8), 271–273 (1980).
   PubMedGoogle Scholar
• Group TE. EuroQol-a new facility for the measurement of health-related quality of life. Health Policy16(3), 199–208 (1990).
   PubMed Web of Science ®Google Scholar
• BrooksR , GroupE. EuroQol: the current state of play. Health Policy37(1), 53–72 (1996).
   PubMed Web of Science ®Google Scholar
• RabinR , CharroFd. EQ-SD: a measure of health status from the EuroQol Group. Ann. Med.33(5), 337–343 (2001).
   PubMed Web of Science ®Google Scholar
• AsherAM , OleiskyER , PenningsJSet al.Measuring clinically relevant improvement after lumbar spine surgery: is it time for something new?Spine J.20(6), 847–856 (2020).
   PubMed Web of Science ®Google Scholar
• BombardierC , HaydenJ , BeatonD. Minimal clinically important difference. Low back pain: outcome measures. J. Rheumatol.28(2), 431–438 (2001).
   PubMed Web of Science ®Google Scholar
• CopayAG , GlassmanSD , SubachBR , BervenS , SchulerTC , CarreonLY. Minimum clinically important difference in lumbar spine surgery patients: a choice of methods using the Oswestry Disability Index, Medical Outcomes Study questionnaire Short Form 36, and pain scales. Spine J.8(6), 968–974 (2008).
   PubMed Web of Science ®Google Scholar
• MaughanEF , LewisJS. Outcome measures in chronic low back pain. Eur. Spine J.19(9), 1484–1494 (2010).
   PubMed Web of Science ®Google Scholar
• VanHornTA , KnioZO , O'GARATJ. Defining a minimum clinically important difference in patient-reported outcome measures in lumbar tubular microdecompression patients. Int. J. Spine Surg.14(4), 538–543 (2020).
   PubMed Web of Science ®Google Scholar
• KarppinenJ , ShenFH , LukKD , AnderssonGB , CheungKM , SamartzisD. Management of degenerative disk disease and chronic low back pain. Orthop. Clin. North Am.42(4), 513–528 (2011).
   PubMed Web of Science ®Google Scholar
• ZhaoL , ManchikantiL , KayeAD , Abd-ElsayedA. Treatment of discogenic low back pain: current treatment strategies and future options—a literature review. Curr. Pain Headache Rep.23(11), 86 (2019).
   PubMed Web of Science ®Google Scholar
• TennyS , GillisCC. Annular Disc Tear.StatPearls Publishing, Treasure Island (FL) (2017).
   Google Scholar
• ManchikantiL , HirschJA. An update on the management of chronic lumbar discogenic pain. Pain Manag.5(5), 373–386 (2015).
   PubMedGoogle Scholar
• UritsI , CapucoA , SharmaMet al.Stem cell therapies for treatment of discogenic low back pain: a comprehensive review. Curr. Pain Headache Rep.23(9), 1–12 (2019).
   PubMed Web of Science ®Google Scholar
• ManchikantiL , CashKA , McManusCD , PampatiV. Fluoroscopic caudal epidural injections in managing chronic axial low back pain without disc herniation, radiculitis, or facet joint pain. J. Pain Res.5, 381 (2012).
   PubMedGoogle Scholar
• NakashimaH , KawakamiN , TsujiTet al.Adjacent segment disease after posterior lumbar interbody fusion. Spine40(14), E831–E841 (2015).
   PubMed Web of Science ®Google Scholar
• ChakravarthyK , ChenY , HeC , ChristoPJ. Stem cell therapy for chronic pain management: review of uses, advances, and adverse effects. Pain Physician20(4), 293–305 (2017).
   PubMed Web of Science ®Google Scholar