Skip to main content
Top
Published in: European Spine Journal 11/2014

01-11-2014 | Original Article

Viability, growth kinetics and stem cell markers of single and clustered cells in human intervertebral discs: implications for regenerative therapies

Authors: Sarah Turner, Birender Balain, Bruce Caterson, Clare Morgan, Sally Roberts

Published in: European Spine Journal | Issue 11/2014

Login to get access

Abstract

Purpose

There is much interest in the development of a cellular therapy for the repair or regeneration of degenerate intervertebral discs (IVDs) utilising autologous cells, with some trials already underway. Clusters of cells are commonly found in degenerate IVDs and are formed via cell proliferation, possibly as a repair response. We investigated whether these clusters may be more suitable as a source of cells for biological repair than the single cells in the IVD.

Methods

Discs were obtained at surgery from 95 patients and used to assess the cell viability, growth kinetics and stem or progenitor cell markers in both the single and clustered cell populations.

Results

Sixty-nine percent (±15) of cells in disc tissue were viable. The clustered cell population consistently proliferated more slowly in monolayer than single cells, although this difference was only significant at P0–1 and P3–4. Both populations exhibited progenitor or notochordal cell markers [chondroitin sulphate epitopes (3B3(−), 7D4, 4C3 and 6C3), Notch-1, cytokeratin 8 and 19] via immunohistochemical examination; stem cell markers assessed with flow cytometry (CD73, 90 and 105 positivity) were similar to those seen on bone marrow-derived mesenchymal stem cells.

Conclusions

These results confirm those of previous studies indicating that progenitor or stem cells reside in adult human intervertebral discs. However, although the cell clusters have arisen via proliferation, there appear to be no greater incidence of these progenitor cells within clusters compared to single cells. Rather, since they proliferate more slowly in vitro than the single cell population, it may be beneficial to avoid the use of clustered cells when sourcing autologous cells for regenerative therapies.
Appendix
Available only for authorised users
Literature
1.
go back to reference Cheung KMC, Karppinen J, Chan D, Ho DWH, Song YQ, Sham P, Cheah KSE, Leong JCY, Luk KDK (2009) Prevalence and pattern of lumbar magnetic resonance imaging changes in a population study of one thousand forty-three individuals. Spine 34:934–940PubMedCrossRef Cheung KMC, Karppinen J, Chan D, Ho DWH, Song YQ, Sham P, Cheah KSE, Leong JCY, Luk KDK (2009) Prevalence and pattern of lumbar magnetic resonance imaging changes in a population study of one thousand forty-three individuals. Spine 34:934–940PubMedCrossRef
2.
go back to reference Adams MA, Roughley PJ (2006) What is intervertebral disc degeneration, and what causes it? Spine 31:2151–2161PubMedCrossRef Adams MA, Roughley PJ (2006) What is intervertebral disc degeneration, and what causes it? Spine 31:2151–2161PubMedCrossRef
3.
go back to reference Bhosale A, Kuiper JH, Johnson WEB, Harrison P, Richardson JB (2009) Midterm to long-term longitudinal outcome of autologous chondrocyte implantation in the knee joint––a multilevel analysis. Am J Sports Med 20:1–8 Bhosale A, Kuiper JH, Johnson WEB, Harrison P, Richardson JB (2009) Midterm to long-term longitudinal outcome of autologous chondrocyte implantation in the knee joint––a multilevel analysis. Am J Sports Med 20:1–8
4.
go back to reference Jungmann PM, Salzmann GM, Schmal H, Pestka JM, Sudkamp NP, Niemeyer P (2012) Autologous chondrocyte implantation for treatment of cartilage defects of the knee: what predicts the need for reintervention? Am J Sports Med 40:58–67PubMedCrossRef Jungmann PM, Salzmann GM, Schmal H, Pestka JM, Sudkamp NP, Niemeyer P (2012) Autologous chondrocyte implantation for treatment of cartilage defects of the knee: what predicts the need for reintervention? Am J Sports Med 40:58–67PubMedCrossRef
5.
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. Euro Spine J 15(3):397–405CrossRef Meisel HJ, Ganey T, Hutton WC, Libera J, Minkus Y, Alasevic O (2006) Clinical experience in cell-based therapeutics: intervention and outcome. Euro Spine J 15(3):397–405CrossRef
7.
go back to reference Trout JJ, Buckwalter JA, Moore KC (1982) Ultrastructure of the human intervertebral disc: II. Cells of the nucleus pulposus. Anat Rec 204:307–314PubMedCrossRef Trout JJ, Buckwalter JA, Moore KC (1982) Ultrastructure of the human intervertebral disc: II. Cells of the nucleus pulposus. Anat Rec 204:307–314PubMedCrossRef
8.
go back to reference Sitte I, Kathrein A, Pfaller K, Pedross F, Roberts S (2009) Intervertebral disc cell death in the porcine and human injured cervical spine after trauma. Spine 34:131–140PubMedCrossRef Sitte I, Kathrein A, Pfaller K, Pedross F, Roberts S (2009) Intervertebral disc cell death in the porcine and human injured cervical spine after trauma. Spine 34:131–140PubMedCrossRef
9.
go back to reference Pritzker KPH (1977) Aging and degeneration in the lumbar intervertebral disc. Orthop Clin N Am 8:65–77 Pritzker KPH (1977) Aging and degeneration in the lumbar intervertebral disc. Orthop Clin N Am 8:65–77
10.
go back to reference Roberts S, Evans EH, Kletsas D, Jaffray DC, Eisenstein SM (2006) Senescence in human intervertebral discs. Eur Spine J 15:S312–S316PubMedCrossRef Roberts S, Evans EH, Kletsas D, Jaffray DC, Eisenstein SM (2006) Senescence in human intervertebral discs. Eur Spine J 15:S312–S316PubMedCrossRef
11.
go back to reference Johnson WEB, Eisenstein SM, Roberts S (2001) Cell cluster formation in degenerate lumbar intervertebral disc is associated with increased disc cell proliferation. Connect Tissue Res 42:197–207PubMedCrossRef Johnson WEB, Eisenstein SM, Roberts S (2001) Cell cluster formation in degenerate lumbar intervertebral disc is associated with increased disc cell proliferation. Connect Tissue Res 42:197–207PubMedCrossRef
12.
go back to reference McGlashan SR, Cluett EC, Jensen CG, Poole CA (2008) Primary cilia in osteoarthritic chondrocytes: from chondrons to clusters. Dev Dyn 237:2013–2020PubMedCrossRef McGlashan SR, Cluett EC, Jensen CG, Poole CA (2008) Primary cilia in osteoarthritic chondrocytes: from chondrons to clusters. Dev Dyn 237:2013–2020PubMedCrossRef
13.
go back to reference Hayes AJ, Tudor D, Nowell MA, Caterson B, Hughes CE (2007) Chondroitin sulfate sulfation motifs as putative biomarkers for isolation of articular cartilage progenitor cells. J Histochem Cytochem 62:125–138CrossRef Hayes AJ, Tudor D, Nowell MA, Caterson B, Hughes CE (2007) Chondroitin sulfate sulfation motifs as putative biomarkers for isolation of articular cartilage progenitor cells. J Histochem Cytochem 62:125–138CrossRef
14.
go back to reference Hayes AJ, Hughes CE, Ralphs JR, Caterson B (2011) Chondroitin sulphate sulphation motif expression in the ontogeny of the intervertebral disc. Eur Cells Mater 21:1–14 Hayes AJ, Hughes CE, Ralphs JR, Caterson B (2011) Chondroitin sulphate sulphation motif expression in the ontogeny of the intervertebral disc. Eur Cells Mater 21:1–14
15.
go back to reference Brisby H, Papadimitriou N, Brantsing C, Bergh P, Lindahl A, Barreto HH (2013) The presence of local mesenchymal progenitor cells in human degenerated intervertebral discs and possibilities to influence these in vitro: a descriptive study in humans. Stem Cells Dev 22:804–814PubMedCrossRef Brisby H, Papadimitriou N, Brantsing C, Bergh P, Lindahl A, Barreto HH (2013) The presence of local mesenchymal progenitor cells in human degenerated intervertebral discs and possibilities to influence these in vitro: a descriptive study in humans. Stem Cells Dev 22:804–814PubMedCrossRef
16.
go back to reference Mead TJ, Yutzey KE (2009) Notch pathway regulation of chondrocyte differentiation and proliferation during appendicular and axial skeleton development. Proc Natl Acad Sci USA 106:14420–14425PubMedCrossRefPubMedCentral Mead TJ, Yutzey KE (2009) Notch pathway regulation of chondrocyte differentiation and proliferation during appendicular and axial skeleton development. Proc Natl Acad Sci USA 106:14420–14425PubMedCrossRefPubMedCentral
17.
go back to reference Khan IM, Palmer EA, Archer CW (2010) Fibroblast growth factor-2 induced chondrocyte cluster formation in experimentally wounded articular cartilage is blocked by soluble Jagged-1. Osteoarthr Cartil 18:208–219PubMedCrossRef Khan IM, Palmer EA, Archer CW (2010) Fibroblast growth factor-2 induced chondrocyte cluster formation in experimentally wounded articular cartilage is blocked by soluble Jagged-1. Osteoarthr Cartil 18:208–219PubMedCrossRef
18.
go back to reference Gruber HE, Gordon B, Norton HJ, Kilburn J, Williams C, Zinchenko N, Heath J, Ingram J, Hanley EN Jr (2008) Analysis of cell death and vertebral end plate bone mineral density in the annulus of the aging sand rat. Spine J 8:475–481PubMedCrossRef Gruber HE, Gordon B, Norton HJ, Kilburn J, Williams C, Zinchenko N, Heath J, Ingram J, Hanley EN Jr (2008) Analysis of cell death and vertebral end plate bone mineral density in the annulus of the aging sand rat. Spine J 8:475–481PubMedCrossRef
19.
go back to reference Khan IM, Bishop JC, Gilbert S, Archer CW (2009) Clonal chondroprogenitors maintain telomerase activity and Sox9 expression during extended monolayer culture and retain chondrogenic potential. Osteoarthr Cartil 17:518–528PubMedCrossRef Khan IM, Bishop JC, Gilbert S, Archer CW (2009) Clonal chondroprogenitors maintain telomerase activity and Sox9 expression during extended monolayer culture and retain chondrogenic potential. Osteoarthr Cartil 17:518–528PubMedCrossRef
20.
go back to reference Gilson A, Dreger M, Urban JP (2010) Differential expression level of cytokeratin 8 in cells of the bovine nucleus pulposus complicates the search for specific intervertebral disc cell markers. Arthritis Res Ther 12:R24PubMedCrossRefPubMedCentral Gilson A, Dreger M, Urban JP (2010) Differential expression level of cytokeratin 8 in cells of the bovine nucleus pulposus complicates the search for specific intervertebral disc cell markers. Arthritis Res Ther 12:R24PubMedCrossRefPubMedCentral
21.
go back to reference Roberts S, Menage J (2004) Microscopic methods for the analysis of engineered tissues. In: Hollander AP, Hatton PV (eds) Methods in molecular biology, vol 238., Biopolymer methods in tissue engineeringHumana Press Inc., Totowa, pp 171–195 Roberts S, Menage J (2004) Microscopic methods for the analysis of engineered tissues. In: Hollander AP, Hatton PV (eds) Methods in molecular biology, vol 238., Biopolymer methods in tissue engineeringHumana Press Inc., Totowa, pp 171–195
22.
go back to reference Johnson WEB, Sivan S, Wright KT, Eisenstein SM, Maroudas A, Roberts S (2006) Human intervertebral disc cells promote nerve growth over substrata of human intervertebral disc aggrecan. Spine 31:1187–1193PubMedCrossRef Johnson WEB, Sivan S, Wright KT, Eisenstein SM, Maroudas A, Roberts S (2006) Human intervertebral disc cells promote nerve growth over substrata of human intervertebral disc aggrecan. Spine 31:1187–1193PubMedCrossRef
23.
go back to reference Wright KT, El Masri W, Osman A, Roberts S, Travedi J, Ashton BA, Johnson WEB (2008) The cell culture expansion of bone marrow stromal cells from humans with spinal cord injury: implications for future cell transplantation therapy. Spinal Cord 46:811–817PubMedCrossRef Wright KT, El Masri W, Osman A, Roberts S, Travedi J, Ashton BA, Johnson WEB (2008) The cell culture expansion of bone marrow stromal cells from humans with spinal cord injury: implications for future cell transplantation therapy. Spinal Cord 46:811–817PubMedCrossRef
24.
go back to reference Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, Peacocke M, Campisi J (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci 92:9363–9367PubMedCrossRefPubMedCentral Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, Peacocke M, Campisi J (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci 92:9363–9367PubMedCrossRefPubMedCentral
25.
go back to reference Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini FC, Krause DS, Deans RJ, Prockop DJ, Horwitz EM (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317PubMedCrossRef Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini FC, Krause DS, Deans RJ, Prockop DJ, Horwitz EM (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317PubMedCrossRef
26.
go back to reference Mennan C, Wright K, Bhattacharjee A, Balain B, Richardson J, Roberts S (2013) Isolation and characterisation of mesenchymal stem cells from different regions of the human umbilical cord. Biomed Res Int 2013:916136PubMedCrossRefPubMedCentral Mennan C, Wright K, Bhattacharjee A, Balain B, Richardson J, Roberts S (2013) Isolation and characterisation of mesenchymal stem cells from different regions of the human umbilical cord. Biomed Res Int 2013:916136PubMedCrossRefPubMedCentral
27.
go back to reference Erskine L, McCaig CD (1997) Integrated interactions between chondroitin sulphate proteoglycans and weak dc electric fields regulate nerve growth cone guidance in vitro. J Cell Sci 110:1957–1966PubMed Erskine L, McCaig CD (1997) Integrated interactions between chondroitin sulphate proteoglycans and weak dc electric fields regulate nerve growth cone guidance in vitro. J Cell Sci 110:1957–1966PubMed
28.
go back to reference Chelberg MK, Banks GM, Geiger DF, Oegema TR Jr (1995) Identification of heterogeneous cell populations in normal human intervertebral disc. J Anat 186(Pt 1):43–53PubMedPubMedCentral Chelberg MK, Banks GM, Geiger DF, Oegema TR Jr (1995) Identification of heterogeneous cell populations in normal human intervertebral disc. J Anat 186(Pt 1):43–53PubMedPubMedCentral
29.
go back to reference Kim JH, Deasy BM, Seo HY, Studer RK, Vo NV, Georgescu HI, Sowa GA, Kang JD (2009) Differentiation of intervertebral notochordal cells through live automated cell imaging system in vitro. Spine (Phila Pa 1976) 34:2486–2493 Kim JH, Deasy BM, Seo HY, Studer RK, Vo NV, Georgescu HI, Sowa GA, Kang JD (2009) Differentiation of intervertebral notochordal cells through live automated cell imaging system in vitro. Spine (Phila Pa 1976) 34:2486–2493
30.
go back to reference Hegewald AA, Endres M, Abbushi A, Cabraja M, Woiciechowsky C, Schmieder K, Kaps C, Thome C (2011) Adequacy of herniated disc tissue as a cell source for nucleus pulposus regeneration. J Neurosurg Spine 14:273–280PubMedCrossRef Hegewald AA, Endres M, Abbushi A, Cabraja M, Woiciechowsky C, Schmieder K, Kaps C, Thome C (2011) Adequacy of herniated disc tissue as a cell source for nucleus pulposus regeneration. J Neurosurg Spine 14:273–280PubMedCrossRef
31.
go back to reference Kassem M, Ankersen L, Eriksen EF, Clark BF, Rattan SI (1997) Demonstration of cellular aging and senescence in serially passaged long-term cultures of human trabecular osteoblasts. Osteoporos Int 7:514–524PubMedCrossRef Kassem M, Ankersen L, Eriksen EF, Clark BF, Rattan SI (1997) Demonstration of cellular aging and senescence in serially passaged long-term cultures of human trabecular osteoblasts. Osteoporos Int 7:514–524PubMedCrossRef
32.
go back to reference Mitsiadis TA, Barrandon O, Rochat A, Barrandon Y, De Bari C (2007) Stem cell niches in mammals. Exp Cell Res 313:3377–3385PubMedCrossRef Mitsiadis TA, Barrandon O, Rochat A, Barrandon Y, De Bari C (2007) Stem cell niches in mammals. Exp Cell Res 313:3377–3385PubMedCrossRef
33.
go back to reference Henriksson H, Thornemo M, Karlsson C, Hagg O, Junevik K, Lindahl A, Brisby H (2009) Identification of cell proliferation zones, progenitor cells and a potential stem cell niche in the intervertebral disc region: a study in four species. Spine (Phila Pa 1976) 34:2278–2287 Henriksson H, Thornemo M, Karlsson C, Hagg O, Junevik K, Lindahl A, Brisby H (2009) Identification of cell proliferation zones, progenitor cells and a potential stem cell niche in the intervertebral disc region: a study in four species. Spine (Phila Pa 1976) 34:2278–2287
34.
go back to reference Henriksson HB, Svala E, Skioldebrand E, Lindahl A, Brisby H (2012) Support of concept that migrating progenitor cells from stem cell niches contribute to normal regeneration of the adult mammal intervertebral disc: a descriptive study in the New Zealand white rabbit. Spine 37:722–732PubMedCrossRef Henriksson HB, Svala E, Skioldebrand E, Lindahl A, Brisby H (2012) Support of concept that migrating progenitor cells from stem cell niches contribute to normal regeneration of the adult mammal intervertebral disc: a descriptive study in the New Zealand white rabbit. Spine 37:722–732PubMedCrossRef
35.
go back to reference Henriksson HB, Brisby H (2013) Development and regeneration potential of the mammalian intervertebral disc. Cells Tissues Organs 197:1–13PubMedCrossRef Henriksson HB, Brisby H (2013) Development and regeneration potential of the mammalian intervertebral disc. Cells Tissues Organs 197:1–13PubMedCrossRef
36.
go back to reference Shu C, Hughes C, Smith SM, Smith MM, Hayes A, Caterson B, Little CB, Melrose J (2013) The ovine newborn and human foetal intervertebral disc contain perlecan and aggrecan variably substituted with native 7D4 CS sulphation motif: spatiotemporal immunolocalisation and co-distribution with Notch-1 in the human foetal disc. Glycoconj J 30:717–725PubMedCrossRef Shu C, Hughes C, Smith SM, Smith MM, Hayes A, Caterson B, Little CB, Melrose J (2013) The ovine newborn and human foetal intervertebral disc contain perlecan and aggrecan variably substituted with native 7D4 CS sulphation motif: spatiotemporal immunolocalisation and co-distribution with Notch-1 in the human foetal disc. Glycoconj J 30:717–725PubMedCrossRef
37.
38.
go back to reference Visco DM, Johnstone B, Hill MA, Jolly GA, Caterson B (1993) Immunohistochemical analysis of 3-B-3(−) and 7-D-4 epitope expression in canine osteoarthritis. Arthritis Rheum 36:1718–1725PubMedCrossRef Visco DM, Johnstone B, Hill MA, Jolly GA, Caterson B (1993) Immunohistochemical analysis of 3-B-3(−) and 7-D-4 epitope expression in canine osteoarthritis. Arthritis Rheum 36:1718–1725PubMedCrossRef
39.
go back to reference Hazell PK, Dent C, Fairclough JA, Bayliss MT, Hardingham TE (1995) Changes in glycosaminoglycan epitope levels in knee joint fluid following injury. Arthritis Rheum 38:953–959PubMedCrossRef Hazell PK, Dent C, Fairclough JA, Bayliss MT, Hardingham TE (1995) Changes in glycosaminoglycan epitope levels in knee joint fluid following injury. Arthritis Rheum 38:953–959PubMedCrossRef
40.
go back to reference Melrose J, Isaacs MD, Smith SM, Hughes CE, Little CB, Caterson B, Hayes AJ (2012) Chondroitin sulphate and heparan sulphate sulphation motifs and their proteoglycans are involved in articular cartilage formation during human foetal knee joint development. Histochem Cell Biol 138(3):461–475 Melrose J, Isaacs MD, Smith SM, Hughes CE, Little CB, Caterson B, Hayes AJ (2012) Chondroitin sulphate and heparan sulphate sulphation motifs and their proteoglycans are involved in articular cartilage formation during human foetal knee joint development. Histochem Cell Biol 138(3):461–475
41.
go back to reference Naka T, Iwamoto Y, Shinohara N, Chuman H, Fukui M, Tsuneyoshi M (1997) Cytokeratin subtyping in chordomas and the fetal notochord: an immunohistochemical analysis of aberrant expression. Mod Pathol 10:545–551PubMed Naka T, Iwamoto Y, Shinohara N, Chuman H, Fukui M, Tsuneyoshi M (1997) Cytokeratin subtyping in chordomas and the fetal notochord: an immunohistochemical analysis of aberrant expression. Mod Pathol 10:545–551PubMed
42.
go back to reference Weiler C, Nerlich AG, Schaaf R, Bachmeier BE, Wuertz K, Boos N (2010) Immunohistochemical identification of notochordal markers in cells in the aging human lumbar intervertebral disc. Eur Spine J 19:1761–1770PubMedCrossRefPubMedCentral Weiler C, Nerlich AG, Schaaf R, Bachmeier BE, Wuertz K, Boos N (2010) Immunohistochemical identification of notochordal markers in cells in the aging human lumbar intervertebral disc. Eur Spine J 19:1761–1770PubMedCrossRefPubMedCentral
43.
go back to reference Sun Z, Wang HQ, Liu ZH, Chang L, Chen YF, Zhang YZ, Zhang WL, Gao Y, Wan ZY, Che L, Liu X, Samartzis D, Luo ZJ (2013) Down-regulated CK8 expression in human intervertebral disc degeneration. Int J Med Sci 10:948–956PubMedCrossRefPubMedCentral Sun Z, Wang HQ, Liu ZH, Chang L, Chen YF, Zhang YZ, Zhang WL, Gao Y, Wan ZY, Che L, Liu X, Samartzis D, Luo ZJ (2013) Down-regulated CK8 expression in human intervertebral disc degeneration. Int J Med Sci 10:948–956PubMedCrossRefPubMedCentral
44.
go back to reference Ralphs JR, Benjamin M, Lewis A, Archer CW (1993) Cytokeratin expression in articular chondrocytes. Trans Orthop Res Soc 18:616 Ralphs JR, Benjamin M, Lewis A, Archer CW (1993) Cytokeratin expression in articular chondrocytes. Trans Orthop Res Soc 18:616
45.
go back to reference Krampera M, Galipeau J, Shi Y, Tarte K, Sensebe L (2013) Immunological characterization of multipotent mesenchymal stromal cells––the International Society for Cellular Therapy (ISCT) working proposal. Cytotherapy 15:1054–1061PubMedCrossRef Krampera M, Galipeau J, Shi Y, Tarte K, Sensebe L (2013) Immunological characterization of multipotent mesenchymal stromal cells––the International Society for Cellular Therapy (ISCT) working proposal. Cytotherapy 15:1054–1061PubMedCrossRef
46.
47.
go back to reference Pilz GA, Braun J, Ulrich C, Felka T, Warstat K, Ruh M, Schewe B, Abele H, Larbi A, Aicher WK (2011) Human mesenchymal stromal cells express CD14 cross-reactive epitopes. Cytometry A 79:635–645PubMedCrossRef Pilz GA, Braun J, Ulrich C, Felka T, Warstat K, Ruh M, Schewe B, Abele H, Larbi A, Aicher WK (2011) Human mesenchymal stromal cells express CD14 cross-reactive epitopes. Cytometry A 79:635–645PubMedCrossRef
48.
go back to reference Meachim G, Cornah MS (1970) Fine structure of juvenile human nucleus pulposus. J Anat 107(Pt 2):337–350 Meachim G, Cornah MS (1970) Fine structure of juvenile human nucleus pulposus. J Anat 107(Pt 2):337–350
49.
go back to reference Bibby SRS, Fairbank J, Urban MR, Urban JPG (2002) Cell viability in scoliotic discs in relation to disc deformity and nutrient levels. Spine 27:2220–2228PubMedCrossRef Bibby SRS, Fairbank J, Urban MR, Urban JPG (2002) Cell viability in scoliotic discs in relation to disc deformity and nutrient levels. Spine 27:2220–2228PubMedCrossRef
50.
go back to reference Tew SR, Kwan APL, Hann A, Thomson BM, Archer CW (2000) The reactions of articular cartilage to experimental wounding. Role of apoptosis. Arthritis Rheum 43:215–225PubMedCrossRef Tew SR, Kwan APL, Hann A, Thomson BM, Archer CW (2000) The reactions of articular cartilage to experimental wounding. Role of apoptosis. Arthritis Rheum 43:215–225PubMedCrossRef
51.
go back to reference Tibiletti M, Kregar-Velikonja N, Urban JP, Fairbank JC (2014) Disc cell therapies: critical issues. Eur Spine J 23(3):375–384 Tibiletti M, Kregar-Velikonja N, Urban JP, Fairbank JC (2014) Disc cell therapies: critical issues. Eur Spine J 23(3):375–384
53.
go back to reference Sharp CA, Roberts S, Evans H, Brown SJ (2009) Disc cell clusters in pathological human intervertebral discs are associated with increased stress protein immunostaining. Eur Spine J 18:1587–1594PubMedCrossRefPubMedCentral Sharp CA, Roberts S, Evans H, Brown SJ (2009) Disc cell clusters in pathological human intervertebral discs are associated with increased stress protein immunostaining. Eur Spine J 18:1587–1594PubMedCrossRefPubMedCentral
54.
go back to reference Sorrell JM, Lintala AM, Mahmoodian F, Caterson B (1988) Epitope-specific changes in chondroitin sulfate/dermatan sulfate proteoglycans as markers in the lymphopoietic and granulopoetic compartments of developing bursae of fabricius. J Immunol 140:4263–4270PubMed Sorrell JM, Lintala AM, Mahmoodian F, Caterson B (1988) Epitope-specific changes in chondroitin sulfate/dermatan sulfate proteoglycans as markers in the lymphopoietic and granulopoetic compartments of developing bursae of fabricius. J Immunol 140:4263–4270PubMed
55.
go back to reference Caterson B, Griffin J, Mahmoodian F, Sorrell JM (1990) Monoclonal antibodies against chondroitin sulphate isomers: their use as probes for investigating proteoglycan metabolism. Biochem Soc Trans 18:820–821PubMed Caterson B, Griffin J, Mahmoodian F, Sorrell JM (1990) Monoclonal antibodies against chondroitin sulphate isomers: their use as probes for investigating proteoglycan metabolism. Biochem Soc Trans 18:820–821PubMed
Metadata
Title
Viability, growth kinetics and stem cell markers of single and clustered cells in human intervertebral discs: implications for regenerative therapies
Authors
Sarah Turner
Birender Balain
Bruce Caterson
Clare Morgan
Sally Roberts
Publication date
01-11-2014
Publisher
Springer Berlin Heidelberg
Published in
European Spine Journal / Issue 11/2014
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI
https://doi.org/10.1007/s00586-014-3500-y

Other articles of this Issue 11/2014

European Spine Journal 11/2014 Go to the issue