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Published in: International Orthopaedics 4/2019

01-04-2019 | Review

Cell therapy for intervertebral disc herniation and degenerative disc disease: clinical trials

Authors: Jordy Schol, Daisuke Sakai

Published in: International Orthopaedics | Issue 4/2019

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Abstract

Low back pain is the primary cause of disability and is highly associated with progression of intervertebral disc degeneration. Current treatment options are limited and fail to address the origin of the problem. New advancements in cellular therapies might offer novel and potent strategies for low back pain patients. In this review, we summarize and discuss the contemporary status of in-human trials investigating cellular transplantation for treatment of low back pain. We aim to highlight current trends, shortcomings, and hurdles for effective clinical trials and consecutive commercialization.
Literature
1.
go back to reference Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V et al (2012) Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the global burden of disease study 2010. Lancet (London, England) 380(9859):2163–2196CrossRef Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V et al (2012) Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the global burden of disease study 2010. Lancet (London, England) 380(9859):2163–2196CrossRef
2.
go back to reference Meucci RD, Fassa AG, Faria NM (2015) Prevalence of chronic low back pain: systematic review. Rev Saude Publica 49:1518–8787 (Electronic)CrossRef Meucci RD, Fassa AG, Faria NM (2015) Prevalence of chronic low back pain: systematic review. Rev Saude Publica 49:1518–8787 (Electronic)CrossRef
3.
go back to reference Katz JN (2006) Lumbar disc disorders and low-back pain: socioeconomic factors and consequences. J Bone Joint Surg Am 88 Suppl 2(4):21–24PubMed Katz JN (2006) Lumbar disc disorders and low-back pain: socioeconomic factors and consequences. J Bone Joint Surg Am 88 Suppl 2(4):21–24PubMed
4.
go back to reference Martin BI, Deyo RA, Mirza SK, Turner JA, Comstock BA, Hollingworth W, Sullivan SD (2008) Expenditures and health status among adults with back and neck problems. Jama 299(6):656–664PubMedCrossRef Martin BI, Deyo RA, Mirza SK, Turner JA, Comstock BA, Hollingworth W, Sullivan SD (2008) Expenditures and health status among adults with back and neck problems. Jama 299(6):656–664PubMedCrossRef
5.
go back to reference Loisel P, Lemaire J, Poitras S, Durand MJ, Champagne F, Stock S, Diallo B, Tremblay C (2002) Cost-benefit and cost-effectiveness analysis of a disability prevention model for back pain management: a six year follow up study. Occup Environ Med 59(12):807–815PubMedPubMedCentralCrossRef Loisel P, Lemaire J, Poitras S, Durand MJ, Champagne F, Stock S, Diallo B, Tremblay C (2002) Cost-benefit and cost-effectiveness analysis of a disability prevention model for back pain management: a six year follow up study. Occup Environ Med 59(12):807–815PubMedPubMedCentralCrossRef
6.
go back to reference Freemont AJ (2009) The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain. Rheumatology (Oxford, England) 48(1):5–10CrossRef Freemont AJ (2009) The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain. Rheumatology (Oxford, England) 48(1):5–10CrossRef
7.
go back to reference Ringwalt C, Gugelmann H, Garrettson M, Dasgupta N, Chung AE, Proescholdbell SK, Skinner AC (2014) Differential prescribing of opioid analgesics according to physician specialty for Medicaid patients with chronic noncancer pain diagnoses. Pain Res Manag 19(4):179–185PubMedPubMedCentralCrossRef Ringwalt C, Gugelmann H, Garrettson M, Dasgupta N, Chung AE, Proescholdbell SK, Skinner AC (2014) Differential prescribing of opioid analgesics according to physician specialty for Medicaid patients with chronic noncancer pain diagnoses. Pain Res Manag 19(4):179–185PubMedPubMedCentralCrossRef
8.
go back to reference Yoshihara H, Yoneoka D (2015) National trends in the surgical treatment for lumbar degenerative disc disease: United States, 2000 to 2009. Spine J 15(2):265–271PubMedCrossRef Yoshihara H, Yoneoka D (2015) National trends in the surgical treatment for lumbar degenerative disc disease: United States, 2000 to 2009. Spine J 15(2):265–271PubMedCrossRef
9.
go back to reference Deyo RA, Nachemson A, Mirza SK (2004) Spinal-fusion surgery—the case for restraint. N Engl J Med 350(7):722–726PubMedCrossRef Deyo RA, Nachemson A, Mirza SK (2004) Spinal-fusion surgery—the case for restraint. N Engl J Med 350(7):722–726PubMedCrossRef
10.
go back to reference Pettine KA, Suzuki RK, Sand TT, Murphy MB (2017) Autologous bone marrow concentrate intradiscal injection for the treatment of degenerative disc disease with three-year follow-up. Int Orthop 41(10):2097–2103PubMedCrossRef Pettine KA, Suzuki RK, Sand TT, Murphy MB (2017) Autologous bone marrow concentrate intradiscal injection for the treatment of degenerative disc disease with three-year follow-up. Int Orthop 41(10):2097–2103PubMedCrossRef
11.
go back to reference Fritzell P, Hagg O, Wessberg P, Nordwall A, Swedish Lumbar Spine Study G (2001) 2001 Volvo award winner in clinical studies: lumbar fusion versus nonsurgical treatment for chronic low back pain: a multicenter randomized controlled trial from the Swedish lumbar spine study group. Spine 26(23):2521–2532 discussion 2532-2524 PubMedCrossRef Fritzell P, Hagg O, Wessberg P, Nordwall A, Swedish Lumbar Spine Study G (2001) 2001 Volvo award winner in clinical studies: lumbar fusion versus nonsurgical treatment for chronic low back pain: a multicenter randomized controlled trial from the Swedish lumbar spine study group. Spine 26(23):2521–2532 discussion 2532-2524 PubMedCrossRef
12.
go back to reference Nguyen TH, Randolph DC, Talmage J, Succop P, Travis R (2011) Long-term outcomes of lumbar fusion among workers’ compensation subjects: a historical cohort study. Spine 36(4):320–331PubMedCrossRef Nguyen TH, Randolph DC, Talmage J, Succop P, Travis R (2011) Long-term outcomes of lumbar fusion among workers’ compensation subjects: a historical cohort study. Spine 36(4):320–331PubMedCrossRef
13.
go back to reference Epstein NE (2015) Adjacent level disease following lumbar spine surgery: a review. Surg Neurol Int 6 Suppl 24:S591–S599CrossRef Epstein NE (2015) Adjacent level disease following lumbar spine surgery: a review. Surg Neurol Int 6 Suppl 24:S591–S599CrossRef
14.
go back to reference Han I, Ropper AE, Konya D, Kabatas S, Toktas Z, Aljuboori Z, Zeng X, Chi JH, Zafonte R, Teng YD (2015) Biological approaches to treating intervertebral disk degeneration: devising stem cell therapies. Cell Transplant 24(11):2197–2208PubMedCrossRef Han I, Ropper AE, Konya D, Kabatas S, Toktas Z, Aljuboori Z, Zeng X, Chi JH, Zafonte R, Teng YD (2015) Biological approaches to treating intervertebral disk degeneration: devising stem cell therapies. Cell Transplant 24(11):2197–2208PubMedCrossRef
15.
go back to reference Buckley CT, Hoyland JA, Fujii K, Pandit A, Iatridis JC, Grad S (2018) Critical aspects and challenges for intervertebral disc repair and regeneration-harnessing advances in tissue engineering. JOR Spine 1:3CrossRef Buckley CT, Hoyland JA, Fujii K, Pandit A, Iatridis JC, Grad S (2018) Critical aspects and challenges for intervertebral disc repair and regeneration-harnessing advances in tissue engineering. JOR Spine 1:3CrossRef
16.
go back to reference Gullbrand SE, Smith LJ, Smith HE, Mauck RL (2018) Promise, progress, and problems in whole disc tissue engineering. JOR Spine 1:2CrossRef Gullbrand SE, Smith LJ, Smith HE, Mauck RL (2018) Promise, progress, and problems in whole disc tissue engineering. JOR Spine 1:2CrossRef
18.
go back to reference Smith LJ, Silverman L, Sakai D, Le Maitre CL, Mauck RL, Malhotra NR, Lotz JC, Buckley CT (2018) Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: recommendations of the ORS spine section. JOR Spine e1036. https://doi.org/10.1002/jsp2.1036 Smith LJ, Silverman L, Sakai D, Le Maitre CL, Mauck RL, Malhotra NR, Lotz JC, Buckley CT (2018) Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: recommendations of the ORS spine section. JOR Spine e1036. https://​doi.​org/​10.​1002/​jsp2.​1036
19.
go back to reference Centeno C, Markle J, Dodson E, Stemper I, Williams CJ, Hyzy M, Ichim T, Freeman M (2017) 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 15(1):197PubMedPubMedCentralCrossRef Centeno C, Markle J, Dodson E, Stemper I, Williams CJ, Hyzy M, Ichim T, Freeman M (2017) 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 15(1):197PubMedPubMedCentralCrossRef
20.
go back to reference Comella K, Silbert R, Parlo M (2017) Effects of the intradiscal implantation of stromal vascular fraction plus platelet rich plasma in patients with degenerative disc disease. J Transl Med 15(1):12PubMedCrossRef Comella K, Silbert R, Parlo M (2017) Effects of the intradiscal implantation of stromal vascular fraction plus platelet rich plasma in patients with degenerative disc disease. J Transl Med 15(1):12PubMedCrossRef
21.
go back to reference Coric D, Pettine K, Sumich A, Boltes MO (2013) Prospective study of disc repair with allogeneic chondrocytes presented at the 2012 Joint Spine Section Meeting. J Neurosurg Spine 18(1):85–95PubMedCrossRef Coric D, Pettine K, Sumich A, Boltes MO (2013) Prospective study of disc repair with allogeneic chondrocytes presented at the 2012 Joint Spine Section Meeting. J Neurosurg Spine 18(1):85–95PubMedCrossRef
22.
go back to reference Elabd C, Centeno CJ, Schultz JR, Lutz G, Ichim T, Silva FJ (2016) 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 14:253PubMedPubMedCentralCrossRef Elabd C, Centeno CJ, Schultz JR, Lutz G, Ichim T, Silva FJ (2016) 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 14:253PubMedPubMedCentralCrossRef
23.
go back to reference Haufe SM, Mork AR (2006) Intradiscal injection of hematopoietic stem cells in an attempt to rejuvenate the intervertebral discs. Stem Cells Dev 15(1):136–137PubMedCrossRef Haufe SM, Mork AR (2006) Intradiscal injection of hematopoietic stem cells in an attempt to rejuvenate the intervertebral discs. Stem Cells Dev 15(1):136–137PubMedCrossRef
24.
go back to reference Kumar H, Ha DH, Lee EJ, Park JH, Shim JH, Ahn TK, Kim KT, Ropper AE, Sohn S, Kim CH et al (2017) 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):262PubMedPubMedCentralCrossRef Kumar H, Ha DH, Lee EJ, Park JH, Shim JH, Ahn TK, Kim KT, Ropper AE, Sohn S, Kim CH et al (2017) 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):262PubMedPubMedCentralCrossRef
25.
go back to reference Meisel HJ, Ganey T, Hutton WC, Libera J, Minkus Y, Alasevic O (2006) Clinical experience in cell-based therapeutics: intervention and outcome. Eur Spine J 15 Suppl 3:S397–S405PubMedCrossRef Meisel HJ, Ganey T, Hutton WC, Libera J, Minkus Y, Alasevic O (2006) Clinical experience in cell-based therapeutics: intervention and outcome. Eur Spine J 15 Suppl 3:S397–S405PubMedCrossRef
26.
go back to reference Meisel HJ, Siodla V, Ganey T, Minkus Y, Hutton WC, Alasevic OJ (2007) Clinical experience in cell-based therapeutics: disc chondrocyte transplantation a treatment for degenerated or damaged intervertebral disc. Biomol Eng 24(1):5–21PubMedCrossRef Meisel HJ, Siodla V, Ganey T, Minkus Y, Hutton WC, Alasevic OJ (2007) Clinical experience in cell-based therapeutics: disc chondrocyte transplantation a treatment for degenerated or damaged intervertebral disc. Biomol Eng 24(1):5–21PubMedCrossRef
27.
go back to reference Mochida J, Sakai D, Nakamura Y, Watanabe T, Yamamoto Y, Kato S (2015) Intervertebral disc repair with activated nucleus pulposus cell transplantation: a three-year, prospective clinical study of its safety. Eur Cell Mater 29:202–212 discussion 212 PubMedCrossRef Mochida J, Sakai D, Nakamura Y, Watanabe T, Yamamoto Y, Kato S (2015) Intervertebral disc repair with activated nucleus pulposus cell transplantation: a three-year, prospective clinical study of its safety. Eur Cell Mater 29:202–212 discussion 212 PubMedCrossRef
28.
go back to reference Noriega DC, Ardura F, Hernandez-Ramajo R, Martin-Ferrero MA, Sanchez-Lite I, Toribio B, Alberca M, Garcia V, Moraleda JM, Sanchez A et al (2017) Intervertebral disc repair by allogeneic mesenchymal bone marrow cells: a randomized controlled trial. Transplantation 101(8):1945–1951PubMedCrossRef Noriega DC, Ardura F, Hernandez-Ramajo R, Martin-Ferrero MA, Sanchez-Lite I, Toribio B, Alberca M, Garcia V, Moraleda JM, Sanchez A et al (2017) Intervertebral disc repair by allogeneic mesenchymal bone marrow cells: a randomized controlled trial. Transplantation 101(8):1945–1951PubMedCrossRef
29.
go back to reference Orozco L, Soler R, Morera C, Alberca M, Sanchez A, Garcia-Sancho J (2011) Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation 92(7):822–828PubMedCrossRef Orozco L, Soler R, Morera C, Alberca M, Sanchez A, Garcia-Sancho J (2011) Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation 92(7):822–828PubMedCrossRef
30.
go back to reference Pang X, Yang H, Peng B (2014) Human umbilical cord mesenchymal stem cell transplantation for the treatment of chronic discogenic low back pain. Pain Physician 17(4):E525–E530PubMed Pang X, Yang H, Peng B (2014) Human umbilical cord mesenchymal stem cell transplantation for the treatment of chronic discogenic low back pain. Pain Physician 17(4):E525–E530PubMed
31.
go back to reference Pettine KA, Murphy MB, Suzuki RK, Sand TT (2015) Percutaneous injection of autologous bone marrow concentrate cells significantly reduces lumbar discogenic pain through 12 months. Stem Cells 33(1):146–156PubMedCrossRef Pettine KA, Murphy MB, Suzuki RK, Sand TT (2015) Percutaneous injection of autologous bone marrow concentrate cells significantly reduces lumbar discogenic pain through 12 months. Stem Cells 33(1):146–156PubMedCrossRef
32.
go back to reference Pettine K, Suzuki R, Sand T, Murphy M (2016) Treatment of discogenic back pain with autologous bone marrow concentrate injection with minimum two year follow-up. Int Orthop 40(1):135–140PubMedCrossRef Pettine K, Suzuki R, Sand T, Murphy M (2016) Treatment of discogenic back pain with autologous bone marrow concentrate injection with minimum two year follow-up. Int Orthop 40(1):135–140PubMedCrossRef
33.
go back to reference Tschugg A, Diepers M, Simone S, Michnacs F, Quirbach S, Strowitzki M, Meisel HJ, Thome C (2017) A prospective randomized multicenter phase I/II clinical trial to evaluate safety and efficacy of NOVOCART disk plus autologous disk chondrocyte transplantation in the treatment of nucleotomized and degenerative lumbar disks to avoid secondary disease: safety results of phase I—a short report. Neurosurg Rev 40(1):155–162PubMedCrossRef Tschugg A, Diepers M, Simone S, Michnacs F, Quirbach S, Strowitzki M, Meisel HJ, Thome C (2017) A prospective randomized multicenter phase I/II clinical trial to evaluate safety and efficacy of NOVOCART disk plus autologous disk chondrocyte transplantation in the treatment of nucleotomized and degenerative lumbar disks to avoid secondary disease: safety results of phase I—a short report. Neurosurg Rev 40(1):155–162PubMedCrossRef
34.
go back to reference Tschugg A, Michnacs F, Strowitzki M, Meisel HJ, Thome C (2016) A prospective multicenter phase I/II clinical trial to evaluate safety and efficacy of NOVOCART disc plus autologous disc chondrocyte transplantation in the treatment of nucleotomized and degenerative lumbar disc to avoid secondary disease: study protocol for a randomized controlled trial. Trials 17(1):108PubMedPubMedCentralCrossRef Tschugg A, Michnacs F, Strowitzki M, Meisel HJ, Thome C (2016) A prospective multicenter phase I/II clinical trial to evaluate safety and efficacy of NOVOCART disc plus autologous disc chondrocyte transplantation in the treatment of nucleotomized and degenerative lumbar disc to avoid secondary disease: study protocol for a randomized controlled trial. Trials 17(1):108PubMedPubMedCentralCrossRef
35.
go back to reference Yoshikawa T, Ueda Y, Miyazaki K, Koizumi M, Takakura Y (2010) Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of two case studies. Spine 35(11):E475–E480PubMedCrossRef Yoshikawa T, Ueda Y, Miyazaki K, Koizumi M, Takakura Y (2010) Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of two case studies. Spine 35(11):E475–E480PubMedCrossRef
36.
go back to reference Thorpe AA, Bach FC, Tryfonidou MA, Le Maitre CL, Mwale F, Diwan AD, Ito K (2018) Leaping the hurdles in developing regenerative treatments for the intervertebral disc from preclinical to clinical. JOR Spine 1:e1027. https://doi.org/10.1002/jsp2.1027 Thorpe AA, Bach FC, Tryfonidou MA, Le Maitre CL, Mwale F, Diwan AD, Ito K (2018) Leaping the hurdles in developing regenerative treatments for the intervertebral disc from preclinical to clinical. JOR Spine 1:e1027. https://​doi.​org/​10.​1002/​jsp2.​1027
37.
go back to reference Holtedahl R, Brox JI, Tjomsland O (2015) Placebo effects in trials evaluating 12 selected minimally invasive interventions: a systematic review and meta-analysis. BMJ Open 5(1):e007331PubMedPubMedCentralCrossRef Holtedahl R, Brox JI, Tjomsland O (2015) Placebo effects in trials evaluating 12 selected minimally invasive interventions: a systematic review and meta-analysis. BMJ Open 5(1):e007331PubMedPubMedCentralCrossRef
38.
go back to reference Harden RN, Saracoglu M, Connolly S, Kirsling A, Comstock K, Khazey K, Gerson T, Burns J (2016) “Managing” the placebo effect: the single-blind placebo lead-in response in two pain models. Pain Med 17(12):2305–2310PubMedCrossRef Harden RN, Saracoglu M, Connolly S, Kirsling A, Comstock K, Khazey K, Gerson T, Burns J (2016) “Managing” the placebo effect: the single-blind placebo lead-in response in two pain models. Pain Med 17(12):2305–2310PubMedCrossRef
39.
go back to reference Brayda-Bruno M, Tibiletti M, Ito K, Fairbank J, Galbusera F, Zerbi A, Roberts S, Wachtel E, Merkher Y, Sivan SS (2014) Advances in the diagnosis of degenerated lumbar discs and their possible clinical application. Eur Spine J 23(3):315–323CrossRef Brayda-Bruno M, Tibiletti M, Ito K, Fairbank J, Galbusera F, Zerbi A, Roberts S, Wachtel E, Merkher Y, Sivan SS (2014) Advances in the diagnosis of degenerated lumbar discs and their possible clinical application. Eur Spine J 23(3):315–323CrossRef
40.
go back to reference Mader KT, Peeters M, Detiger SE, Helder MN, Smit TH, Le Maitre CL, Sammon C (2016) Investigation of intervertebral disc degeneration using multivariate FTIR spectroscopic imaging. Faraday Discuss 187:393–414PubMedPubMedCentralCrossRef Mader KT, Peeters M, Detiger SE, Helder MN, Smit TH, Le Maitre CL, Sammon C (2016) Investigation of intervertebral disc degeneration using multivariate FTIR spectroscopic imaging. Faraday Discuss 187:393–414PubMedPubMedCentralCrossRef
41.
go back to reference Wang AM, Cao P, Yee A, Chan D, Wu EX (2015) Detection of extracellular matrix degradation in intervertebral disc degeneration by diffusion magnetic resonance spectroscopy. Magn Reson Med 73(5):1703–1712PubMedCrossRef Wang AM, Cao P, Yee A, Chan D, Wu EX (2015) Detection of extracellular matrix degradation in intervertebral disc degeneration by diffusion magnetic resonance spectroscopy. Magn Reson Med 73(5):1703–1712PubMedCrossRef
42.
go back to reference Grad S, Bow C, Karppinen J, Luk KD, Cheung KM, Alini M, Samartzis D (2016) Systemic blood plasma CCL5 and CXCL6: potential biomarkers for human lumbar disc degeneration. Eur Cell Mater 31:1–10PubMedCrossRef Grad S, Bow C, Karppinen J, Luk KD, Cheung KM, Alini M, Samartzis D (2016) Systemic blood plasma CCL5 and CXCL6: potential biomarkers for human lumbar disc degeneration. Eur Cell Mater 31:1–10PubMedCrossRef
43.
go back to reference Davies BM, Atkinson RA, Ludwinski F, Freemont AJ, Hoyland JA, Gnanalingham KK (2016) Qualitative grading of disc degeneration by magnetic resonance in the lumbar and cervical spine: lack of correlation with histology in surgical cases. Br J Neurosurg 30(4):414–421PubMedCrossRef Davies BM, Atkinson RA, Ludwinski F, Freemont AJ, Hoyland JA, Gnanalingham KK (2016) Qualitative grading of disc degeneration by magnetic resonance in the lumbar and cervical spine: lack of correlation with histology in surgical cases. Br J Neurosurg 30(4):414–421PubMedCrossRef
44.
go back to reference Nukaga T, Sakai D, Tanaka M, Hiyama A, Nakai T, Mochida J (2016) Transplantation of activated nucleus pulposus cells after cryopreservation: efficacy study in a canine disc degeneration model. Eur Cell Mater 31:1473–2262 (Electronic), 95-106 Nukaga T, Sakai D, Tanaka M, Hiyama A, Nakai T, Mochida J (2016) Transplantation of activated nucleus pulposus cells after cryopreservation: efficacy study in a canine disc degeneration model. Eur Cell Mater 31:1473–2262 (Electronic), 95-106
45.
go back to reference Gantenbein B, Calandriello E, Wuertz-Kozak K, Benneker LM, Keel MJ, Chan SC (2014) Activation of intervertebral disc cells by co-culture with notochordal cells, conditioned medium and hypoxia. BMC Musculoskelet Disord 15(1):422PubMedPubMedCentralCrossRef Gantenbein B, Calandriello E, Wuertz-Kozak K, Benneker LM, Keel MJ, Chan SC (2014) Activation of intervertebral disc cells by co-culture with notochordal cells, conditioned medium and hypoxia. BMC Musculoskelet Disord 15(1):422PubMedPubMedCentralCrossRef
46.
go back to reference Hiraishi S, Schol J, Sakai D, Nukaga T, Erickson I, Silverman L, Foley K, Watanabe M (2018) Discogenic cell transplantation directly from a cryopreserved state in an induced intervertebral disc degeneration canine model. JOR Spine 1:2CrossRef Hiraishi S, Schol J, Sakai D, Nukaga T, Erickson I, Silverman L, Foley K, Watanabe M (2018) Discogenic cell transplantation directly from a cryopreserved state in an induced intervertebral disc degeneration canine model. JOR Spine 1:2CrossRef
47.
go back to reference Ganey T, Libera J, Moos V, Alasevic O, Fritsch KG, Meisel HJ, Hutton WC (2003) Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc. Spine 28(23):2609–2620PubMedCrossRef Ganey T, Libera J, Moos V, Alasevic O, Fritsch KG, Meisel HJ, Hutton WC (2003) Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc. Spine 28(23):2609–2620PubMedCrossRef
48.
go back to reference Arpinar VE, Rand SD, Klein AP, Maiman DJ, Muftuler LT (2015) Changes in perfusion and diffusion in the endplate regions of degenerating intervertebral discs: a DCE-MRI study. Eur Spine J 24(11):2458–2467PubMedCrossRef Arpinar VE, Rand SD, Klein AP, Maiman DJ, Muftuler LT (2015) Changes in perfusion and diffusion in the endplate regions of degenerating intervertebral discs: a DCE-MRI study. Eur Spine J 24(11):2458–2467PubMedCrossRef
49.
go back to reference Muftuler LT, Jarman JP, Yu HJ, Gardner VO, Maiman DJ, Arpinar VE (2015) Association between intervertebral disc degeneration and endplate perfusion studied by DCE-MRI. Eur Spine J 24(4):679–685PubMedCrossRef Muftuler LT, Jarman JP, Yu HJ, Gardner VO, Maiman DJ, Arpinar VE (2015) Association between intervertebral disc degeneration and endplate perfusion studied by DCE-MRI. Eur Spine J 24(4):679–685PubMedCrossRef
50.
go back to reference Clarke LE, McConnell JC, Sherratt MJ, Derby B, Richardson SM, Hoyland JA (2014) Growth differentiation factor 6 and transforming growth factor-beta differentially mediate mesenchymal stem cell differentiation, composition, and micromechanical properties of nucleus pulposus constructs. Arthritis Res Ther 16(2):R67PubMedPubMedCentralCrossRef Clarke LE, McConnell JC, Sherratt MJ, Derby B, Richardson SM, Hoyland JA (2014) Growth differentiation factor 6 and transforming growth factor-beta differentially mediate mesenchymal stem cell differentiation, composition, and micromechanical properties of nucleus pulposus constructs. Arthritis Res Ther 16(2):R67PubMedPubMedCentralCrossRef
51.
go back to reference Colombier P, Clouet J, Boyer C, Ruel M, Bonin G, Lesoeur J, Moreau A, Fellah BH, Weiss P, Lescaudron L et al (2016) TGF-beta1 and GDF5 act synergistically to drive the differentiation of human adipose stromal cells toward nucleus pulposus-like cells. Stem Cells 34(3):653–667PubMedCrossRef Colombier P, Clouet J, Boyer C, Ruel M, Bonin G, Lesoeur J, Moreau A, Fellah BH, Weiss P, Lescaudron L et al (2016) TGF-beta1 and GDF5 act synergistically to drive the differentiation of human adipose stromal cells toward nucleus pulposus-like cells. Stem Cells 34(3):653–667PubMedCrossRef
52.
go back to reference Stoyanov JV, Gantenbein-Ritter B, Bertolo A, Aebli N, Baur M, Alini M, Grad S (2011) Role of hypoxia and growth and differentiation factor-5 on differentiation of human mesenchymal stem cells towards intervertebral nucleus pulposus-like cells. Eur Cell Mater 21:533–547PubMedCrossRef Stoyanov JV, Gantenbein-Ritter B, Bertolo A, Aebli N, Baur M, Alini M, Grad S (2011) Role of hypoxia and growth and differentiation factor-5 on differentiation of human mesenchymal stem cells towards intervertebral nucleus pulposus-like cells. Eur Cell Mater 21:533–547PubMedCrossRef
53.
go back to reference Mwale F, Roughley P, Antoniou J (2004) Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: a requisite for tissue engineering of intervertebral disc. Eur Cell Mater 8:58–63 discussion 63-54 PubMedCrossRef Mwale F, Roughley P, Antoniou J (2004) Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: a requisite for tissue engineering of intervertebral disc. Eur Cell Mater 8:58–63 discussion 63-54 PubMedCrossRef
54.
go back to reference Sakai D, Nakamura Y, Nakai T, Mishima T, Kato S, Grad S, Alini M, Risbud MV, Chan D, Cheah KS et al (2012) Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc. Nat Commun 3:1264PubMedCrossRef Sakai D, Nakamura Y, Nakai T, Mishima T, Kato S, Grad S, Alini M, Risbud MV, Chan D, Cheah KS et al (2012) Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc. Nat Commun 3:1264PubMedCrossRef
55.
go back to reference Sakai D, Schol J, Bach FC, Tekari A, Sagawa N, Nakamura Y, Chan SCW, Nakai T, Creemers LB, Frauchiger DA et al. (2018) Successful fishing for nucleus pulposus progenitor cells of the intervertebral disc across species. JOR Spine 1:e1018. https://doi.org/10.1002/jsp2.1018 Sakai D, Schol J, Bach FC, Tekari A, Sagawa N, Nakamura Y, Chan SCW, Nakai T, Creemers LB, Frauchiger DA et al. (2018) Successful fishing for nucleus pulposus progenitor cells of the intervertebral disc across species. JOR Spine 1:e1018. https://​doi.​org/​10.​1002/​jsp2.​1018
56.
go back to reference Wu T, Song HX, Dong Y, Li JH (2018) Cell-based therapies for lumbar discogenic low back pain: systematic review and single-arm meta-analysis. Spine 43(1):49–57PubMedCrossRef Wu T, Song HX, Dong Y, Li JH (2018) Cell-based therapies for lumbar discogenic low back pain: systematic review and single-arm meta-analysis. Spine 43(1):49–57PubMedCrossRef
57.
go back to reference Ganguly P, El-Jawhari JJ, Giannoudis PV, Burska AN, Ponchel F, Jones EA (2017) Age-related changes in bone marrow mesenchymal stromal cells: a potential impact on osteoporosis and osteoarthritis development. Cell Transplant 26(9):1520–1529PubMedPubMedCentralCrossRef Ganguly P, El-Jawhari JJ, Giannoudis PV, Burska AN, Ponchel F, Jones EA (2017) Age-related changes in bone marrow mesenchymal stromal cells: a potential impact on osteoporosis and osteoarthritis development. Cell Transplant 26(9):1520–1529PubMedPubMedCentralCrossRef
58.
go back to reference Serigano K, Sakai D, Hiyama A, Tamura F, Tanaka M, Mochida J (2010) Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model. J Orthop Res 28(10):1267–1275PubMedCrossRef Serigano K, Sakai D, Hiyama A, Tamura F, Tanaka M, Mochida J (2010) Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model. J Orthop Res 28(10):1267–1275PubMedCrossRef
59.
go back to reference Michalek AJ, Buckley MR, Bonassar LJ, Cohen I, Iatridis JC (2010) The effects of needle puncture injury on microscale shear strain in the intervertebral disc annulus fibrosus. Spine J 10(12):1098–1105PubMedPubMedCentralCrossRef Michalek AJ, Buckley MR, Bonassar LJ, Cohen I, Iatridis JC (2010) The effects of needle puncture injury on microscale shear strain in the intervertebral disc annulus fibrosus. Spine J 10(12):1098–1105PubMedPubMedCentralCrossRef
60.
go back to reference Gullbrand SE, Malhotra NR, Schaer TP, Zawacki Z, Martin JT, Bendigo JR, Milby AH, Dodge GR, Vresilovic EJ, Elliott DM et al (2017) A large animal model that recapitulates the spectrum of human intervertebral disc degeneration. Osteoarthr Cartil 25(1):146–156CrossRef Gullbrand SE, Malhotra NR, Schaer TP, Zawacki Z, Martin JT, Bendigo JR, Milby AH, Dodge GR, Vresilovic EJ, Elliott DM et al (2017) A large animal model that recapitulates the spectrum of human intervertebral disc degeneration. Osteoarthr Cartil 25(1):146–156CrossRef
61.
go back to reference Vadala G, Sowa G, Hubert M, Gilbertson LG, Denaro V, Kang JD (2012) Mesenchymal stem cells injection in degenerated intervertebral disc: cell leakage may induce osteophyte formation. J Tissue Eng Regen Med 6(5):348–355PubMedCrossRef Vadala G, Sowa G, Hubert M, Gilbertson LG, Denaro V, Kang JD (2012) Mesenchymal stem cells injection in degenerated intervertebral disc: cell leakage may induce osteophyte formation. J Tissue Eng Regen Med 6(5):348–355PubMedCrossRef
62.
go back to reference Vadala G, Russo F, Pattappa G, Schiuma D, Peroglio M, Benneker LM, Grad S, Alini M, Denaro V (2013) The transpedicular approach as an alternative route for intervertebral disc regeneration. Spine 38(6):E319–E324PubMedCrossRef Vadala G, Russo F, Pattappa G, Schiuma D, Peroglio M, Benneker LM, Grad S, Alini M, Denaro V (2013) The transpedicular approach as an alternative route for intervertebral disc regeneration. Spine 38(6):E319–E324PubMedCrossRef
63.
go back to reference Illien-Junger S, Pattappa G, Peroglio M, Benneker LM, Stoddart MJ, Sakai D, Mochida J, Grad S, Alini M (2012) Homing of mesenchymal stem cells in induced degenerative intervertebral discs in a whole organ culture system. Spine 37(22):1865–1873PubMedCrossRef Illien-Junger S, Pattappa G, Peroglio M, Benneker LM, Stoddart MJ, Sakai D, Mochida J, Grad S, Alini M (2012) Homing of mesenchymal stem cells in induced degenerative intervertebral discs in a whole organ culture system. Spine 37(22):1865–1873PubMedCrossRef
64.
go back to reference Sakai D, Schol J, Foldager CB, Sato M, Watanabe M (2017) Regenerative technologies to bed side: evolving the regulatory framework. J Orthop Translat 9:1–7PubMedPubMedCentralCrossRef Sakai D, Schol J, Foldager CB, Sato M, Watanabe M (2017) Regenerative technologies to bed side: evolving the regulatory framework. J Orthop Translat 9:1–7PubMedPubMedCentralCrossRef
Metadata
Title
Cell therapy for intervertebral disc herniation and degenerative disc disease: clinical trials
Authors
Jordy Schol
Daisuke Sakai
Publication date
01-04-2019
Publisher
Springer Berlin Heidelberg
Published in
International Orthopaedics / Issue 4/2019
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-018-4223-1

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