Please note this is a comparison between Version 2 by Bruce Ren and Version 1 by Benjamin Gantenbein.
Chronic low back pain (LBP) remains a challenging condition to treat, and especially to cure. If conservative treatment approaches fail, the current “gold standard” for intervertebral disc degeneration (IDD)-provoked back pain is spinal fusion. However, due to its invasive and destructive nature, the focus of orthopedic research related to the intervertebral disc (IVD) has shifted more towards cell-based therapeutic approaches. They aim to reduce or even reverse the degenerative cascade by mimicking the human body’s physiological healing system. The implementation of progenitor and/or stem cells and, in particular, the delivery of mesenchymal stromal cells (MSCs) has revealed significant potential to cure the degenerated/injured IVD.
mesenchymal stromal cells
homing
cell-based therapy
intervertebral disc regeneration
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References
Oichi, T.; Taniguchi, Y.; Oshima, Y.; Tanaka, S.; Saito, T. Pathomechanism of intervertebral disc degeneration. JOR Spine 2020, 3, e1076.
DALYs, G.B.D.; Collaborators, H. Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017, 390, 1260–1344.
Hartvigsen, J.; Hancock, M.J.; Kongsted, A.; Louw, Q.; Ferreira, M.L.; Genevay, S.; Hoy, D.; Karppinen, J.; Pransky, G.; Sieper, J.; et al. What low back pain is and why we need to pay attention. Lancet 2018, 391, 2356–2367.
Bevan, S.; Quadrello, T.; McGee, R.; Mahdon, M.; Vavrovsky, A.; Barham, L. Fit for Work? Musculoskeletal Disorders in the European Workforce: Fit for Work Europe; Part of Lancaster University: Lancashire, UK, 2009.
Hoy, D.; Bain, C.; Williams, G.; March, L.; Brooks, P.; Blyth, F.; Woolf, A.; Vos, T.; Buchbinder, R. A systematic review of the global prevalence of low back pain. Arthritis Rheum 2012, 64, 2028–2037.
Katz, J.N. Lumbar disc disorders and low-back pain: Socioeconomic factors and consequences. J. Bone Jt. Surg. Am. 2006, 88 (Suppl. 2), 21–24.
Macfarlane, G.J.; Thomas, E.; Croft, P.R.; Papageorgiou, A.C.; Jayson, M.I.; Silman, A.J. Predictors of early improvement in low back pain amongst consulters to general practice: The influence of pre-morbid and episode-related factors. Pain 1999, 80, 113–119.
Dunn, K.M.; Hestbaek, L.; Cassidy, J.D. Low back pain across the life course. Best Pract. Res. Clin. Rheumatol. 2013, 27, 591–600.
Golob, A.L.; Wipf, J.E. Low back pain. Med. Clin. N. Am. 2014, 98, 405–428.
Cheung, K.M.; Karppinen, J.; Chan, D.; Ho, D.W.; Song, Y.Q.; Sham, P.; Cheah, K.S.; Leong, J.C.; Luk, K.D. Prevalence and pattern of lumbar magnetic resonance imaging changes in a population study of one thousand forty-three individuals. Spine 2009, 34, 934–940.
White, A.A., 3rd; Panjabi, M.M. The basic kinematics of the human spine. A review of past and current knowledge. Spine 1978, 3, 12–20.
Sun, Z.; Liu, B.; Luo, Z.J. The Immune Privilege of the Intervertebral Disc: Implications for Intervertebral Disc Degeneration Treatment. Int. J. Med. Sci. 2020, 17, 685–692.
Cassidy, J.J.; Hiltner, A.; Baer, E. Hierarchical structure of the intervertebral disc. Connect Tissue Res. 1989, 23, 75–88.
Adams, P.; Eyre, D.R.; Muir, H. Biochemical aspects of development and ageing of human lumbar intervertebral discs. Rheumatol. Rehabil. 1977, 16, 22–29.
Inoue, H.; Takeda, T. Three-dimensional observation of collagen framework of lumbar intervertebral discs. Acta Orthop. Scand. 1975, 46, 949–956.
Sakai, D.; Andersson, G.B. Stem cell therapy for intervertebral disc regeneration: Obstacles and solutions. Nat. Rev. Rheumatol. 2015, 11, 243–256.
Urban, J.P.; Smith, S.; Fairbank, J.C. Nutrition of the intervertebral disc. Spine 2004, 29, 2700–2709.
Kurunlahti, M.; Tervonen, O.; Vanharanta, H.; Ilkko, E.; Suramo, I. Association of atherosclerosis with low back pain and the degree of disc degeneration. Spine 1999, 24, 2080–2084.
Johnstone, B.; Bayliss, M.T. The large proteoglycans of the human intervertebral disc. Changes in their biosynthesis and structure with age, topography, and pathology. Spine 1995, 20, 674–684.
Risbud, M.V.; Shapiro, I.M. Role of cytokines in intervertebral disc degeneration: Pain and disc content. Nat. Rev. Rheumatol. 2014, 10, 44–56.
Freemont, A.J.; Peacock, T.E.; Goupille, P.; Hoyland, J.A.; O’Brien, J.; Jayson, M.I. Nerve ingrowth into diseased intervertebral disc in chronic back pain. Lancet 1997, 350, 178–181.
Carreon, L.Y.; Ito, T.; Yamada, M.; Uchiyama, S.; Takahashi, H.E. Neovascularization induced by anulus and its inhibition by cartilage endplate. Its role in disc absorption. Spine 1997, 22, 1429–1434.
Kadow, T.; Sowa, G.; Vo, N.; Kang, J.D. Molecular basis of intervertebral disc degeneration and herniations: What are the important translational questions? Clin. Orthop. Relat. Res. 2015, 473, 1903–1912.
Luoma, K.; Riihimaki, H.; Luukkonen, R.; Raininko, R.; Viikari-Juntura, E.; Lamminen, A. Low back pain in relation to lumbar disc degeneration. Spine 2000, 25, 487–492.
Qaseem, A.; Wilt, T.J.; McLean, R.M.; Forciea, M.A.; Clinical Guidelines Committee of the American College of Physicians. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann. Intern. Med. 2017, 166, 514–530.
Vas, J.; Aranda, J.M.; Modesto, M.; Benitez-Parejo, N.; Herrera, A.; Martinez-Barquin, D.M.; Aguilar, I.; Sanchez-Araujo, M.; Rivas-Ruiz, F. Acupuncture in patients with acute low back pain: A multicentre randomised controlled clinical trial. Pain 2012, 153, 1883–1889.
Lee, J.H.; Choi, T.Y.; Lee, M.S.; Lee, H.; Shin, B.C.; Lee, H. Acupuncture for acute low back pain: A systematic review. Clin. J. Pain 2013, 29, 172–185.
Saper, R.B.; Lemaster, C.; Delitto, A.; Sherman, K.J.; Herman, P.M.; Sadikova, E.; Stevans, J.; Keosaian, J.E.; Cerrada, C.J.; Femia, A.L.; et al. Yoga, Physical Therapy, or Education for Chronic Low Back Pain. Ann. Intern. Med. 2017, 167.
Chou, R.; Cote, P.; Randhawa, K.; Torres, P.; Yu, H.; Nordin, M.; Hurwitz, E.L.; Haldeman, S.; Cedraschi, C. The Global Spine Care Initiative: Applying evidence-based guidelines on the non-invasive management of back and neck pain to low- and middle-income communities. Eur. Spine J. 2018, 27, 851–860.
May, R.D.; Frauchiger, D.A.; Albers, C.E.; Benneker, L.M.; Kohl, S.; Gantenbein, B. Inhibitory Effects of Human Primary Intervertebral Disc Cells on Human Primary Osteoblasts in a Co-Culture System. Int. J. Mol. Sci. 2018, 19, 1195.
De Kunder, S.L.; Rijkers, K.; Caelers, I.; de Bie, R.A.; Koehler, P.J.; van Santbrink, H. Lumbar Interbody Fusion: A Historical Overview and a Future Perspective. Spine 2018, 43, 1161–1168.
Bodalia, P.N.; Balaji, V.; Kaila, R.; Wilson, L. Effectiveness and safety of recombinant human bone morphogenetic protein-2 for adults with lumbar spine pseudarthrosis following spinal fusion surgery: A systematic review. Bone Jt. Res. 2016, 5, 145–152.
May, R.D.; Frauchiger, D.A.; Albers, C.E.; Tekari, A.; Benneker, L.M.; Klenke, F.M.; Hofstetter, W.; Gantenbein, B. Application of Cytokines of the Bone Morphogenetic Protein (BMP) Family in Spinal Fusion—Effects on the Bone, Intervertebral Disc and Mesenchymal Stromal Cells. Curr. Stem Cell Res. Ther. 2019, 14, 618–643.
Wang, X.; Wanyan, P.; Tian, J.H.; Hu, L. Meta-analysis of randomized trials comparing fusion surgery to non-surgical treatment for discogenic chronic low back pain. J. Back Musculoskelet. Rehabil. 2015, 28, 621–627.
Harris, I.A.; Traeger, A.; Stanford, R.; Maher, C.G.; Buchbinder, R. Lumbar spine fusion: What is the evidence? Intern. Med. J. 2018, 48, 1430–1434.
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, 306–324.
Sakai, D.; Nakamura, Y.; Nakai, T.; Mishima, T.; Kato, S.; Grad, S.; Alini, M.; Risbud, M.V.; Chan, D.; Cheah, K.S.; et al. Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc. Nat. Commun. 2012, 3, 1264.
Takahashi, K.; Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006, 126, 663–676.
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, E475–E480.
Sheikh, H.; Zakharian, K.; De La Torre, R.P.; Facek, C.; Vasquez, A.; Chaudhry, G.R.; Svinarich, D.; Perez-Cruet, M.J. In vivo intervertebral disc regeneration using stem cell-derived chondroprogenitors. J. Neurosurg. Spine 2009, 10, 265–272.
Vadala, G.; Ambrosio, L.; Russo, F.; Papalia, R.; Denaro, V. Interaction between Mesenchymal Stem Cells and Intervertebral Disc Microenvironment: From Cell Therapy to Tissue Engineering. Stem Cells Int. 2019, 2019, 2376172.
Liu, Z.J.; Zhuge, Y.; Velazquez, O.C. Trafficking and differentiation of mesenchymal stem cells. J. Cell Biochem. 2009, 106, 984–991.
Caplan, A.I. Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J. Cell Physiol. 2007, 213, 341–347.
Bertolo, A.; Thiede, T.; Aebli, N.; Baur, M.; Ferguson, S.J.; Stoyanov, J.V. Human mesenchymal stem cell co-culture modulates the immunological properties of human intervertebral disc tissue fragments in vitro. Eur. Spine J. 2011, 20, 592–603.
Shim, E.K.; Lee, J.S.; Kim, D.E.; Kim, S.K.; Jung, B.J.; Choi, E.Y.; Kim, C.S. Autogenous Mesenchymal Stem Cells from the Vertebral Body Enhance Intervertebral Disc Regeneration via Paracrine Interaction: An in Vitro Pilot Study. Cell Transpl. 2016, 25, 1819–1832.
Stoyanov, J.V.; Gantenbein-Ritter, B.; Bertolo, A.; Aebli, N.; Baur, M.; Alini, M.; Grad, S. 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. 2011, 21, 533–547.
Clarke, L.E.; McConnell, J.C.; Sherratt, M.J.; Derby, B.; Richardson, S.M.; Hoyland, J.A. 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. 2014, 16, R67.
Berebichez-Fridman, R.; Gomez-Garcia, R.; Granados-Montiel, J.; Berebichez-Fastlicht, E.; Olivos-Meza, A.; Granados, J.; Velasquillo, C.; Ibarra, C. The Holy Grail of Orthopedic Surgery: Mesenchymal Stem Cells-Their Current Uses and Potential Applications. Stem Cells Int. 2017, 2017, 2638305.
Hodgkinson, T.; Shen, B.; Diwan, A.; Hoyland, J.A.; Richardson, S.M. Therapeutic potential of growth differentiation factors in the treatment of degenerative disc diseases. JOR Spine 2019, 2, e1045.
Lyu, F.J.; Cheung, K.M.; Zheng, Z.; Wang, H.; Sakai, D.; Leung, V.Y. IVD progenitor cells: A new horizon for understanding disc homeostasis and repair. Nat. Rev. Rheumatol. 2019, 15, 102–112.
Kraus, P.; Lufkin, T. Implications for a Stem Cell Regenerative Medicine Based Approach to Human Intervertebral Disk Degeneration. Front. Cell Dev. Biol. 2017, 5, 17.
Loibl, M.; Wuertz-Kozak, K.; Vadala, G.; Lang, S.; Fairbank, J.; Urban, J.P. Controversies in regenerative medicine: Should intervertebral disc degeneration be treated with mesenchymal stem cells? JOR Spine 2019, 2, e1043.
Ma, K.; Chen, S.; Li, Z.; Deng, X.; Huang, D.; Xiong, L.; Shao, Z. Mechanisms of endogenous repair failure during intervertebral disc degeneration. Osteoarthr. Cartil. 2019, 27, 41–48.
Melrose, J. Strategies in regenerative medicine for intervertebral disc repair using mesenchymal stem cells and bioscaffolds. Regen. Med. 2016, 11, 705–724.
Piazza, N.; Dehghani, M.; Gaborski, T.R.; Wuertz-Kozak, K. Therapeutic Potential of Extracellular Vesicles in Degenerative Diseases of the Intervertebral Disc. Front. Bioeng. Biotechnol. 2020, 8, 311.
Richardson, S.M.; Kalamegam, G.; Pushparaj, P.N.; Matta, C.; Memic, A.; Khademhosseini, A.; Mobasheri, R.; Poletti, F.L.; Hoyland, J.A.; Mobasheri, A. Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration. Methods 2016, 99, 69–80.
Urits, I.; Capuco, A.; Sharma, M.; Kaye, A.D.; Viswanath, O.; Cornett, E.M.; Orhurhu, V. Stem Cell Therapies for Treatment of Discogenic Low Back Pain: A Comprehensive Review. Curr. Pain Headache Rep. 2019, 23, 65.
Vadala, G.; Russo, F.; Ambrosio, L.; Papalia, R.; Denaro, V. Mesenchymal stem cells for intervertebral disc regeneration. J. Biol. Regul. Homeost. Agents 2016, 30, 173–179.
Vadala, G.; Russo, F.; Ambrosio, L.; Loppini, M.; Denaro, V. Stem cells sources for intervertebral disc regeneration. World J. Stem Cells 2016, 8, 185–201.
Stergar, J.; Gradisnik, L.; Velnar, T.; Maver, U. Intervertebral disc tissue engineering: A brief review. Bosn. J. Basic Med. Sci. 2019, 19, 130–137.
Frauchiger, D.A.; Heeb, S.R.; May, R.D.; Woltje, M.; Benneker, L.M.; Gantenbein, B. Differentiation of MSC and annulus fibrosus cells on genetically engineered silk fleece-membrane-composites enriched for GDF-6 or TGF-beta3. J. Orthop. Res. 2018, 36, 1324–1333.
Peroglio, M.; Eglin, D.; Benneker, L.M.; Alini, M.; Grad, S. Thermoreversible hyaluronan-based hydrogel supports in vitro and ex vivo disc-like differentiation of human mesenchymal stem cells. Spine J. 2013, 13, 1627–1639.
Zhang, C.; Gullbrand, S.E.; Schaer, T.P.; Boorman, S.; Elliott, D.M.; Chen, W.; Dodge, G.R.; Mauck, R.L.; Malhotra, N.R.; Smith, L.J. Combined Hydrogel and Mesenchymal Stem Cell Therapy for Moderate-Severity Disc Degeneration in Goats. Tissue Eng. Part A 2020.
Sun, B.; Lian, M.; Han, Y.; Mo, X.; Jiang, W.; Qiao, Z.; Dai, K. A 3D-Bioprinted dual growth factor-releasing intervertebral disc scaffold induces nucleus pulposus and annulus fibrosus reconstruction. Bioact. Mater. 2021, 6, 179–190.
Karp, J.M.; Leng Teo, G.S. Mesenchymal stem cell homing: The devil is in the details. Cell Stem Cell 2009, 4, 206–216.
Migliorini, F.; Rath, B.; Tingart, M.; Baroncini, A.; Quack, V.; Eschweiler, J. Autogenic mesenchymal stem cells for intervertebral disc regeneration. Int. Orthop. 2019, 43, 1027–1036.
Orozco, L.; Soler, R.; Morera, C.; Alberca, M.; Sanchez, A.; Garcia-Sancho, J. Intervertebral disc repair by autologous mesenchymal bone marrow cells: A pilot study. Transplantation 2011, 92, 822–828.
Noriega, D.C.; Ardura, F.; Hernandez-Ramajo, R.; Martin-Ferrero, M.A.; Sanchez-Lite, I.; Toribio, B.; Alberca, M.; Garcia, V.; Moraleda, J.M.; Sanchez, A.; et al. Intervertebral Disc Repair by Allogeneic Mesenchymal Bone Marrow Cells: A Randomized Controlled Trial. Transplantation 2017, 101, 1945–1951.
Centeno, C.; Markle, J.; Dodson, E.; Stemper, I.; Williams, C.J.; Hyzy, M.; Ichim, T.; Freeman, M. 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, 197.
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, 12.
Elabd, C.; Centeno, C.J.; Schultz, J.R.; Lutz, G.; Ichim, T.; Silva, F.J. 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, 253.
Kumar, H.; Ha, D.H.; Lee, E.J.; Park, J.H.; Shim, J.H.; Ahn, T.K.; Kim, K.T.; Ropper, A.E.; Sohn, S.; Kim, C.H.; 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, 262.
Pettine, K.A.; Suzuki, R.K.; Sand, T.T.; Murphy, M.B. Autologous bone marrow concentrate intradiscal injection for the treatment of degenerative disc disease with three-year follow-up. Int. Orthop. 2017, 41, 2097–2103.
Michalek, A.J.; Buckley, M.R.; Bonassar, L.J.; Cohen, I.; Iatridis, J.C. The effects of needle puncture injury on microscale shear strain in the intervertebral disc annulus fibrosus. Spine J. 2010, 10, 1098–1105.
Carragee, E.J.; Don, A.S.; Hurwitz, E.L.; Cuellar, J.M.; Carrino, J.A.; Herzog, R. 2009 ISSLS Prize Winner: Does discography cause accelerated progression of degeneration changes in the lumbar disc: A ten-year matched cohort study. Spine 2009, 34, 2338–2345.
Hu, M.H.; Yang, K.C.; Chen, Y.J.; Sun, Y.H.; Lin, F.H.; Yang, S.H. Optimization of puncture injury to rat caudal disc for mimicking early degeneration of intervertebral disc. J. Orthop. Res. 2018, 36, 202–211.
Issy, A.C.; Castania, V.; Castania, M.; Salmon, C.E.; Nogueira-Barbosa, M.H.; Bel, E.D.; Defino, H.L. Experimental model of intervertebral disc degeneration by needle puncture in Wistar rats. Braz. J. Med. Biol. Res. 2013, 46, 235–244.
Vadala, G.; Sowa, G.; Hubert, M.; Gilbertson, L.G.; Denaro, V.; Kang, J.D. Mesenchymal stem cells injection in degenerated intervertebral disc: Cell leakage may induce osteophyte formation. J. Tissue Eng. Regen. Med. 2012, 6, 348–355.
Huang, Y.C.; Leung, V.Y.; Lu, W.W.; Luk, K.D. The effects of microenvironment in mesenchymal stem cell-based regeneration of intervertebral disc. Spine J. 2013, 13, 352–362.
Wu, G.D.; Nolta, J.A.; Jin, Y.S.; Barr, M.L.; Yu, H.; Starnes, V.A.; Cramer, D.V. Migration of mesenchymal stem cells to heart allografts during chronic rejection. Transplantation 2003, 75, 679–685.
Chen, J.; Li, Y.; Wang, L.; Lu, M.; Zhang, X.; Chopp, M. Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats. J. Neurol. Sci. 2001, 189, 49–57.
Shafei, A.E.; Ali, M.A.; Ghanem, H.G.; Shehata, A.I.; Abdelgawad, A.A.; Handal, H.R.; Talaat, K.A.; Ashaal, A.E.; El-Shal, A.S. Mesenchymal stem cell therapy: A promising cell-based therapy for treatment of myocardial infarction. J. Gene Med. 2017, 19.
Barbash, I.M.; Chouraqui, P.; Baron, J.; Feinberg, M.S.; Etzion, S.; Tessone, A.; Miller, L.; Guetta, E.; Zipori, D.; Kedes, L.H.; et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: Feasibility, cell migration, and body distribution. Circulation 2003, 108, 863–868.
Shahror, R.A.; Ali, A.A.A.; Wu, C.C.; Chiang, Y.H.; Chen, K.Y. Enhanced Homing of Mesenchymal Stem Cells Overexpressing Fibroblast Growth Factor 21 to Injury Site in a Mouse Model of Traumatic Brain Injury. Int. J. Mol. Sci. 2019, 20, 2624.
Fan, M.; Zhang, J.; Xin, H.; He, X.; Zhang, X. Current Perspectives on Role of MSC in Renal Pathophysiology. Front. Physiol. 2018, 9, 1323.
Shao, Y.; Zhou, F.; He, D.; Zhang, L.; Shen, J. Overexpression of CXCR7 promotes mesenchymal stem cells to repair phosgene-induced acute lung injury in rats. Biomed. Pharmacother. 2019, 109, 1233–1239.
Yao, W.; Lay, Y.E.; Kot, A.; Liu, R.; Zhang, H.; Chen, H.; Lam, K.; Lane, N.E. Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference. Stem Cells 2016, 34, 2587–2600.
Sakai, D.; Nishimura, K.; Tanaka, M.; Nakajima, D.; Grad, S.; Alini, M.; Kawada, H.; Ando, K.; Mochida, J. Migration of bone marrow-derived cells for endogenous repair in a new tail-looping disc degeneration model in the mouse: A pilot study. Spine J. 2015, 15, 1356–1365.
Illien-Junger, S.; Pattappa, G.; Peroglio, M.; Benneker, L.M.; Stoddart, M.J.; Sakai, D.; Mochida, J.; Grad, S.; Alini, M. Homing of mesenchymal stem cells in induced degenerative intervertebral discs in a whole organ culture system. Spine 2012, 37, 1865–1873.
Ponte, A.L.; Marais, E.; Gallay, N.; Langonne, A.; Delorme, B.; Herault, O.; Charbord, P.; Domenech, J. The in vitro migration capacity of human bone marrow mesenchymal stem cells: Comparison of chemokine and growth factor chemotactic activities. Stem Cells 2007, 25, 1737–1745.
Lapidot, T.; Kollet, O. The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD/SCID and NOD/SCID/B2m(null) mice. Leukemia 2002, 16, 1992–2003.
Pereira, C.L.; Goncalves, R.M.; Peroglio, M.; Pattappa, G.; D’Este, M.; Eglin, D.; Barbosa, M.A.; Alini, M.; Grad, S. The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the recruitment of MSCs in degenerating intervertebral discs. Biomaterials 2014, 35, 8144–8153.
Pattappa, G.; Peroglio, M.; Sakai, D.; Mochida, J.; Benneker, L.M.; Alini, M.; Grad, S. CCL5/RANTES is a key chemoattractant released by degenerative intervertebral discs in organ culture. Eur. Cell Mater. 2014, 27, 124–136.
Wangler, S.; Menzel, U.; Li, Z.; Ma, J.; Hoppe, S.; Benneker, L.M.; Alini, M.; Grad, S.; Peroglio, M. CD146/MCAM distinguishes stem cell subpopulations with distinct migration and regenerative potential in degenerative intervertebral discs. Osteoarthr. Cartil. 2019, 27, 1094–1105.
Tam, V.; Rogers, I.; Chan, D.; Leung, V.Y.; Cheung, K.M. A comparison of intravenous and intradiscal delivery of multipotential stem cells on the healing of injured intervertebral disk. J. Orthop. Res. 2014, 32, 819–825.
Cunha, C.; Almeida, C.R.; Almeida, M.I.; Silva, A.M.; Molinos, M.; Lamas, S.; Pereira, C.L.; Teixeira, G.Q.; Monteiro, A.T.; Santos, S.G.; et al. Systemic Delivery of Bone Marrow Mesenchymal Stem Cells for In Situ Intervertebral Disc Regeneration. Stem Cells Transl. Med. 2017, 6, 1029–1039.
Gruber, H.E.; Ashraf, N.; Kilburn, J.; Williams, C.; Norton, H.J.; Gordon, B.E.; Hanley, E.N., Jr. Vertebral endplate architecture and vascularization: Application of micro-computerized tomography, a vascular tracer, and immunocytochemistry in analyses of disc degeneration in the aging sand rat. Spine 2005, 30, 2593–2600.
Hassler, O. The human intervertebral disc. A micro-angiographical study on its vascular supply at various ages. Acta Orthop. Scand. 1969, 40, 765–772.
Pereira, C.L.; Teixeira, G.Q.; Ribeiro-Machado, C.; Caldeira, J.; Costa, M.; Figueiredo, F.; Fernandes, R.; Aguiar, P.; Grad, S.; Barbosa, M.A.; et al. Mesenchymal Stem/Stromal Cells seeded on cartilaginous endplates promote Intervertebral Disc Regeneration through Extracellular Matrix Remodeling. Sci. Rep. 2016, 6, 33836.
Wangler, S.; Peroglio, M.; Menzel, U.; Benneker, L.M.; Haglund, L.; Sakai, D.; Alini, M.; Grad, S. Mesenchymal Stem Cell Homing Into Intervertebral Discs Enhances the Tie2-positive Progenitor Cell Population, Prevents Cell Death, and Induces a Proliferative Response. Spine 2019, 44, 1613–1622.