Prospects of stem cell therapy in osteoarthritis

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibliography

• 1  Schroeppel JP, Crist JD, Anderson HC, Wang J: Molecular regulation of articular chondrocyte function and its significance in osteoarthritis. Histol. Histopathol.26(3),377–394 (2011).
  Medline CASGoogle Scholar
• 2  Sun HB: Mechanical loading, cartilage degradation, and arthritis. Ann. NY Acad. Sci.1211,37–50 (2010).
  Medline CASGoogle Scholar
• 3  Goldring SR, Goldring MB: Bone and cartilage in osteoarthritis: is what’s best for one good or bad for the other? Arthritis Res. Ther.12,143 (2011).
  Google Scholar
• 4  Evangelou E, Valdes AM, Kerkhof HJ, Styrkarsdottir U, Zhu Y, Meulenbelt I: Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22. Ann. Rheum. Dis.70,349–355 (2011).
  Medline CASGoogle Scholar
• 5  Malchau H, Herberts P, Garellick G, Soderman P, Eisler T: Prognosis of total hip replacement: update of results and risk-ratio analysis for revision and re-revision from the Swedish National Hip Arthoplasty Register 1979–2000. Scientific Exhibition. Presented at: 69th Annual Meeting of the American Academy of Orthopaedic Surgeons. Dallas, TX, USA, 11–15 June 2002.
  Google Scholar
• 6  Chen FH, Tuan RS: Mesenchymal stem cells in arthritic diseases. Arthritis Res. Ther.10(5),223 (2008).
  MedlineGoogle Scholar
• 7  Johnson MH, McConnell JM: Lineage allocation and cell polarity during mouse embryogenesis. Sem. Cell Dev. Biol.15(5),583–597 (2004).
  Medline CASGoogle Scholar
• 8  Evans MJ , Kaufman MH: Establishment in culture of pluripotent cells from mouse embryos. Nature292(5819),154–156 (1981).
  Medline CASGoogle Scholar
• 9  Martin GR: Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc. Natl Acad. Sci. USA78(12),7634–7638 (1981).
  Medline CASGoogle Scholar
• 10  Bongso A, Fong CY, Ng SC, Ratnam S: Isolation and culture of inner cell mass cells from human blastocytes. Hum. Reprod.9(11),2110–2117 (1994).
  Medline CASGoogle Scholar
• 11  Thomson JA, Itskovitz-Eldor J, Shapiro SS et al.: Embryonic stem cell lines derived from human blastocytes. Science282(5391),1145–1147 (1998).
  Medline CASGoogle Scholar
• 12  Nichols J, Zevnik B, Anastassiadis K et al.: Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell95(3),379–391 (1998).
  Medline CASGoogle Scholar
• 13  Chambers I, Colby D, Robertson M et al.: Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell113(5),643–655 (2003).
  Medline CASGoogle Scholar
• 14  Rodda DJ, Chew JL, Lim LH et al.: Transcriptional regulation of nanog by OCT4 and SOX2. J. Biol. Chem.280(26),24731–24737 (2005).
  Medline CASGoogle Scholar
• 15  Johansson H, Simonsson S: Core transcription factors, Oct4 Sox2 and Nanog, individually form complexes with nucleophosmin (Npm1) to control embryonic stem (ES) cell fate determination. Aging2(11),1–8 (2010).
  MedlineGoogle Scholar
• 16  Boyer LA, Plath K, Zeitlinger J et al.: Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature441(7091),349–353 (2006).
  Medline CASGoogle Scholar
• 17  Lee JH, Hart SR, Skalnik DG: Histone deacetylase activity is required for embryonic stem cell differentiation. Genesis38(1),32–38 (2004).
  Medline CASGoogle Scholar
• 18  Meshorer E, Misteli T: Chromatin in pluripotent embryonic stem cells and differentiation. Nat. Rev. Mol. Cell Biol.7(7),540–546 (2006).
  Medline CASGoogle Scholar
• 19  Efroni S, Duttagupta R, Cheng J et al.: Global transcription in pluripotent embryonic stem cells. Cell Stem Cell2(5),437–447 (2008).
  Medline CASGoogle Scholar
• 20  Houbaviy HB, Murray MF, Sharp PA: Embryonic stem cell-specific microRNAs. Dev. Cell5(2),351–358 (2003).
  Medline CASGoogle Scholar
• 21  Kanellopoulou C, Muljo SA, Kung AL et al.: Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev.19(4),489–501 (2010).
  Google Scholar
• 22  Kim NW, Piatyszek MA, Prowse KR et al.: Specific association of human telomerase activity with immortal cells and cancer. Science266(5193),2011–2015 (1994).
  Medline CASGoogle Scholar
• 23  Miura T, Mattson MP, Roa MS: Cellular lifespan and senescence signaling in embryonic stem cells. Aging Cell3(6),333–343 (2010).
  Google Scholar
• 24  Zhong XY, Zhang B, Asadollahi R, Low SH, Holzgreve W: Umbilical blood stem cells: what to expect. Ann. NY Acad. Sci.1205,17–22 (2010).
  MedlineGoogle Scholar
• 25  Gluckman E, Broxmeyer HA, Auerbach AD et al.: Hematopoietic reconstruction in a patient with Fanconi’s anemia by means of umilical-cord blood from an HLA-identical sibling. N. Engl. J. Med.321(17),1174–1178 (1989).
  Medline CASGoogle Scholar
• 26  Quintin A, Schizas C, Scaletta C et al.: Isolation and in vitro chondrogenic potential of human fetal spine cells. J. Cell. Mol. Med.13,2559–2569 (2009).
  MedlineGoogle Scholar
• 27  O’Donoghue K, Fisk NM: Fetal stem cells. Best Pract. Res. Clin. Obstet. Gynaecol.18(6),853–875 (2004).
  MedlineGoogle Scholar
• 28  Gucciardo L, Lories R, Ochsenbein-Kolble N, Done E, Zwijsen A, Deprest J: Fetal mesenchymal stem cells: isolation, properties and potential use in perinatology and regenerative medicine. Br. J. Obstet. Gynaecol.116(2),166–172 (2009).
  CASGoogle Scholar
• 29  Pappa KL, Anganou NP: Novel sources of fetal stem cells: where do they fit on the deveopmental continuum? Regen. Med.4(3),423–433 (2009).
  Google Scholar
• 30  Kita K, Gauglitz GG, Phan TT, Herndon DN, Jeschke MG: Isolation and characterization of mesenchymal stem cells from the sub-amniotic human ubilical lining membrane. Stem Cells Dev.19(4),491–502 (2010).
  Medline CASGoogle Scholar
• 31  Takahashi K, Yamanaka S: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell126(4),663–676 (2006).▪▪ Landmark paper that demonstrated for the first time that adult cells could be reprogrammed to a pluripotent embryonic stem cell-like state by introducing as few as four key transcription factors.
  Medline CASGoogle Scholar
• 32  Takahashi K, Tanabe K, Ohnuki M et al.: Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell131(5),861–872 (2007).
  Medline CASGoogle Scholar
• 33  Wernig M, Meissner A, Foreman R et al.: In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature448(7151),318–324 (2007).
  Medline CASGoogle Scholar
• 34  Yu J, Vodyanik MA, Smuga-Otto K et al.: Induced pluripotent stem cell lines derived from human somatic cells. Science318(5858),1917–1920 (2007).
  Medline CASGoogle Scholar
• 35  Kim K, Doi A, Wen B: Epigenetic memory in induced pluripotent stem cellls. Nature467(7313),285–290 (2010).
  Medline CASGoogle Scholar
• 36  Pasi CE, Dedreli-Oz A, Negrini Set al.: Genomic instability in induced stem cells. Cell Death Diff.18(5),745–753(2011).
  Medline CASGoogle Scholar
• 37  Huangfu D, Osafune K, Maehr R et al.: Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat. Biotechnol.26(11),1269–1275 (2008).
  Medline CASGoogle Scholar
• 38  Woltjen K, Michale IP, Mohseni P et al.: A piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature458(7239),766–770 (2009).
  Medline CASGoogle Scholar
• 39  Kaji K, Norrby K, Paca A, Mileikovsky M, Mohseni P, Woltjen K: Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature458(7239),771–775 (2009).
  Medline CASGoogle Scholar
• 40  Nakagawa M, Takizawa N, Narita M, Ichisaka T, Yamanaka S: Promotion of direct reprogramming by transformation-deficient Myc. Proc. Natl Acad. Sci. USA107(32),14152–14157 (2010).
  Medline CASGoogle Scholar
• 41  Flores I, Blasco MA: The role of telomeres and telomerase in stem cell aging. Fed. Eur. Biochem. Soc. Lett.584(17),3826–3830 (2010).
  Medline CASGoogle Scholar
• 42  Scadden DT: The stem cell niche as an entity of action. Nature441(7097),1075–1079 (2006).
  Medline CASGoogle Scholar
• 43  Friedenstein AJ, Chailakhjan RK, Lalykina KS: The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Res.3(4),393–403 (1970).▪▪ Colony formation identified as an important indicator of ‘stem cell-ness’.
  CASGoogle Scholar
• 44  Caplan AI: Mesenchymal stem cells. J. Orthop. Res.9(5),641–650 (1991).
  Medline CASGoogle Scholar
• 45  Horwitz EM, Le Blanc K, Dominici M et al.: Clarification of the nomenclature for MSC: the International Society for Cellular Therapy position statement. Cytotherapy7(5),393–395 (2005).
  Medline CASGoogle Scholar
• 46  Bianco P, Robey PG, Saggio I, Riminucci M: Mesenchymal stem cells in human bone marrow (skeletal stem cells): a critical discussion of their nature, identity and significance in incurable skeletal disease. Hum. Gene Ther.21(9),1057–1066 (2010).
  Medline CASGoogle Scholar
• 47  da Silva ML, Chagatelles PC, Nardi NB: Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J. Cell Sci.119(11),2204–2213 (2006).
  MedlineGoogle Scholar
• 48  Pittenger MF, Mackay AM, Beck SC et al.: Multilineage potential of human mesenchymal stem cells. Science284,143–147 (1999).▪ Provides evidence of existence of multipotent mesenchymal stem cells (MSCs) in bone marrow.
  Medline CASGoogle Scholar
• 49  Dominici M, Le Blanc K, Mueller I et al.: Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular position statement. Cytotherapy8(4),315–317 (2006).
  Medline CASGoogle Scholar
• 50  Simmons PJ, Torok-Storb B: Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood78(1),55–62 (1991).
  Medline CASGoogle Scholar
• 51  Jones EA, Kinsey SE, English A et al.: Isolation and characterization of bone marrow multipotential mesenchymal progenitor cells. Arthritis Rheum.46(12),3349–3360 (2002).
  MedlineGoogle Scholar
• 52  Sacchetti B, Funari A, Michienzi S et al.: Self-renewing osteoprogenitors in bone marrow sinusoids can organise a hematopoietic microenvironment. Cell131(2),324–336 (2007).▪▪ Provides first evidence of self-renewal of bone marrow MSCs via serial transplantation.
  Medline CASGoogle Scholar
• 53  Barzilay R, Melamed E, Offen D: Introducing transcription factors to multipotent mesenchymal stem cells: making transdifferentiation possible. Stem Cells27(10),2590–2515 (2009).
  Google Scholar
• 54  Frith J, Genever P: Transcriptional control of mesenchymal stem cell differentiation. Transf. Med. Hemother.35(3),216–227 (2008).
  Google Scholar
• 55  Jaiswal N, Haynesworth SE, Caplan AI, Bruder SP: Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro.J. Cell. Biochem.64(2),295–312 (1997).
  Medline CASGoogle Scholar
• 56  de Crombrugghe B, Lefebvre V, Behringer RR, Bi W, Murakami S, Huang W: Transcriptional mechanisms of chondrocyte differentiation. Matrix Biol.19,389–394 (2000).
  Medline CASGoogle Scholar
• 57  Zhou G, Zheng Q, Engin F et al.: Dominance of SOX9 function over RUNX2 during skeletogenesis. Proc. Natl Acad. Sci. USA103(50),19004–19009 (2006).
  Medline CASGoogle Scholar
• 58  Cheng A, Genever PG: SOX9 determines RUNX transactivity by directing intracellular degradation. J. Miner. Res.25(12),2404–2413 (2010).
  CASGoogle Scholar
• 59  Si YL, Zhao YL, Hao HJ, Fu XB, Han WD: MSCs: biological characteristics, clinical applications and their outstanding concerns. Ageing Res. Rev.10(1),93–103 (2011).
  Medline CASGoogle Scholar
• 60  Hoogduijn MJ, Popp F, Verbeek R et al.: The immunomodulatory properties of mesenchymal stem cells and their use for immunotherapy. Int. Immunopharmacol.10(12),1496–1500 (2010).
  Medline CASGoogle Scholar
• 61  Liu Y, Mu R, Wang S et al.: Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis. Arthritis Res. Ther.12(6),R210 (2010).
  MedlineGoogle Scholar
• 62  Di Nicola M, Carlo-Stella C, Magni M et al.: Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood99,3838–3843 (2002).
  Medline CASGoogle Scholar
• 63  Popp FC, Eggenhofer E, Renner P et al.: Mesenchymal stem cells can induce long-term acceptance of solid organ allografts in synergy with low-dose mycophenolate. Transplant Immunol.20,55–60 (2008).
  Medline CASGoogle Scholar
• 64  Bartholomew A, Sturgeon C, Siatskas M et al.: Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp. Haematol.30,42–48 (2002).
  MedlineGoogle Scholar
• 65  Aggarwal S, Pittenger MF: Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood105,1815–1822 (2005).
  Medline CASGoogle Scholar
• 66  Yao C, Sakata D, Esaki Y et al.: Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion. Nat. Med.15,633–640 (2009).
  Medline CASGoogle Scholar
• 67  Yanez R, Oviedo A, Aldea M, Bueren JA, Lamana ML: Prostaglandin E2 plays a key role in the immunosuppressive properties of adipose and bone marrow tissue-derived mesenchymal stromal cells. Exp. Cell Res.316,3109–3123 (2010).
  Medline CASGoogle Scholar
• 68  Sbano P, Cuccia A, Mazzanti B et al.: Use of donor bone marrow mesenchymal stem cells for treatment of skin allograft rejection in a preclinical rat model. Arch. Dermatol. Res.300(3),115–124 (2008).
  MedlineGoogle Scholar
• 69  Mias C, Lairez O, Trouche E et al.: Mesenchymal stem cells promote matrix metalloproteinase secretion by cardiac fibroblasts and reduce cardiac ventricle fibrosis after myocardial infarction. Stem Cells27(11),2734–2743 (2009).
  Medline CASGoogle Scholar
• 70  Yagi H, Soto-Guitierrez A, Parekkadan B et al.: Mesenchymal stem cells: mechanisms of immunomodulation and homing. Cell Transplant.19(6),667–679 (2010).
  MedlineGoogle Scholar
• 71  Chamberlain G, Fox J, Ashton B, Middleton J: Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells25,2739–2749 (2007).
  Medline CASGoogle Scholar
• 72  Ding C, Cicuttini F, Cooley H, Boon C, Jones G: Natural history of knee cartilage defects and factors affecting change. Arch. Int. Med.166(6),651–658 (2006).
  MedlineGoogle Scholar
• 73  Messner K, Maletius W: The long-term prognosis for severe damage to weight-bearing cartilage in the knee: a 14 year clinical and radiographic follow-up in 28 young athletes. Acta Orthop. Scand.67(2),165–168 (1996).
  Medline CASGoogle Scholar
• 74  Shelbourne KD, Jari S, Gray T: Outcome of untreated traumatic articular cartilage defects of the knee: a natural history study. J. Bone Joint Surg. Am.85A(Suppl. 2),8–16 (2003).
  Google Scholar
• 75  Shapiro F, Koide S, Glimcher MJ: Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. J. Bone Joint Surg. Am.75A(4),532–553 (1993).
  Google Scholar
• 76  Eltawil NM, De Bari C, Achan P,Pitzalis C, Dell’Accio F: A novel in vivo murine model of cartilage regeneration. Age and strain-dependent outcome after joint surface injury. Osteoarthritis Cart.17(6),695–704 (2009).
  Medline CASGoogle Scholar
• 77  Lee CH, Cook JL, Mendelson A, Moioli EK, Yao H, Mao JJ: Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study. Lancet7(376),440–448 (2010).
  Google Scholar
• 78  Jones EA, English A, Henshaw K et al.: Enumeration and phenotypic characterization of synovial fluid multipotential mesenchymal stem cells in inflammatory and degenerative arthritis. Arthritis Rheum.50(3),315–317 (2004).
  Google Scholar
• 79  De Bari C, Dell’Accio F, Tylzanowski P, Luyten FP: Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum.44(8),1928–1942 (2001).
  Medline CASGoogle Scholar
• 80  De Bari C, Dell’Accio F, Vandenabeele F, Vermeesch JR, Raymackers JM, Luyten F: Skeletal muscle repair by adult human mesenchymal stem cells from synovial membrane. J. Cell Biol.160(6),909–918 (2003).
  Medline CASGoogle Scholar
• 81  De Bari C, Dell’Accio F, Luyten F:Human periosteum-derived cells maintain phenotypic stability and chondrogenic potential throughout expansion regardless of donor age. Arthritis Rheum.44(1),85–95 (2001).
  Medline CASGoogle Scholar
• 82  De Bari C, Dell’Accio F, Vanlauwe J et al.: Mesenchymal multipotency of adult human periosteal cells demonstrated by single-cell lineage analysis. Arthritis Rheum.54(4),1209–1221 (2006).
  Medline CASGoogle Scholar
• 83  Nakahara H, Dennis JE, Bruder SP, Haynesworth SE, Lennon DP, Caplan A: In vitro differentiation of bone and hypertrophic cartilage from periosteal-derived cells. Exp. Cell Res.195,492–503 (1991).
  Medline CASGoogle Scholar
• 84  Sakai D: Biological treatment: future beyond cell transplantation. Proc. World Forum Spine Res. (2010) (Epub ahead of print).
  Google Scholar
• 85  Zuk PA, Zhu M, Ashjian P et al.:Human adipose tissue is a source of multipotent stem cells. Mol. Biol. Cell13,4279–4295 (2002).
  Medline CASGoogle Scholar
• 86  Dowthwaite GP, Bishop JC, Redman SN et al.: The surface of articular cartilage contains a progenitor cell population. J. Cell Sci.117,889–897 (2004).
  Medline CASGoogle Scholar
• 87  Williams R, Khan IM, Richardson K et al.: Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. PLoS One5(10),1–14 (2010).
  Google Scholar
• 88  Shi S , Gronthos S: Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J. Bone Miner. Res.18(4),696–704 (2003).
  MedlineGoogle Scholar
• 89  De Bari C, Pringle S, Pitzalis C, Dell’Accio F: The stem cell niche: a new target in medicine. Curr. Opin. Orthop.17(5),398–404 (2006).
  Google Scholar
• 90  da Silva ML, Caplan AI, Nardi NB: In search of the in vivo identity of mesenchymal stem cells. Stem Cells26(9),2287–2299 (2008).
  MedlineGoogle Scholar
• 91  Khan IM, Bishop JC, Gilbert S, Archer CW: Clonal chondroprogenitors maintain telomerase activity and Sox9 expression during extended monolayer culture and retain chondrogenic potential. Osteoarthritis Cart.17,518–528 (2009).
  Medline CASGoogle Scholar
• 92  Koelling S, Krugel J, Irmer M et al.: Migratory chondrogenic progenitor cells from repair tissue during the later stages of human osteoarthritis. Cell Stem Cell4(4),324–335 (2009).
  Medline CASGoogle Scholar
• 93  Koelling S, Miosge N: Sex differences of chondrogenic progenitor cells in late stages of osteoarthritis. Arthritis Rheum.62(4),1077–1087 (2010).
  Medline CASGoogle Scholar
• 94  English A, Jones EA, Corscadden D et al.: A comparative assessment of cartilage and joint fat pad as a potential source of cells for autologous therapy development in knee osteoarthritis. Rheumatology46,1676–1683 (2007).
  Medline CASGoogle Scholar
• 95  Yarak S, Okamoto OK: Human adipose-derived stem cells: current challenges and clinical perspectives. An. Bras. Dermatol.85(5),647–656 (2010).
  MedlineGoogle Scholar
• 96  Kurth TB, Dell’Accio F, Crouch V, Augello A, Sharpe PT, De Bari C: Functional mesenchymal stem cell niches in the adult knee joint synovium in vivo.Arthritis Rheum. (2010) (Epub ahead of print).▪ Provides first evidence of existence of endogenous MSCs in the adult synovium in vivo.
  Google Scholar
• 97  Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L: Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N. Engl. J. Med.331(6),889–895 (1994).
  Medline CASGoogle Scholar
• 98  Meisel HJ, Siodla V, Ganey T, Minkus Y, Hutton WC, Alasevic O: Clinical experience in cell-based therapeutics: disc chondrocyte transplantation – a treatment for degenerated or damaged intervertebral disc. Biomol. Eng.24,5–21 (2006).
  MedlineGoogle Scholar
• 99  Bajada S, Harrison PE, Ashton BA, Cassar-Pullicino VN, Ashammakhi N, Richardson JB: Successful treatment of refactory tibial nonunion using calcium sulphate and bone marrow stromal cell implantation. J. Bone Joint Surg. Br.89,1382–1386 (2007).
  Medline CASGoogle Scholar
• 100  Centeno CJ, Schultz JR, Cheever M, Robinson B, Freeman M, Marasco W: Safety and compliations reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique. Curr. Stem Cell Res. Ther.5,81–93 (2010).
  Medline CASGoogle Scholar
• 101  Bhosale A, Kuiper JH, Johnson WEB, Harrison P, Richardson JB: Midterm to long-term longitudinal outcome of autologous chondrocyte implantation in the knee joint – a multilevel analysis. Am. J. Sports Med.20(10),1–8 (2009).
  Google Scholar
• 102  Hollander AP, Dickinson SC, Sims TJ, Soranzo C, Pavesio A: Quantitative analysis of repair tissue biopsies following chondrocyte implantation. Tissue Eng. Cart. Bone249,218–233 (2003).
  Google Scholar
• 103  Haddo O, Mahroof S, Higgs D et al.: The use of chondrogide membrane in autologous chondrocyte implantation. Knee11,51–55 (2004).
  MedlineGoogle Scholar
• 104  Zheng M-H, Willers C, Kirilak L et al.: Matrix-induced autologous chondrocyte implantation (MACI): biological and histological assessment. Tissue Eng.13(4),737–746 (2007).
  Medline CASGoogle Scholar
• 105  Kreuz PC, Muller S, Ossendorf C, Kaps C, Erggelet C: Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: four-year clinical results. Arthritis Res. Ther.11(2),R33 (2009).
  MedlineGoogle Scholar
• 106  Warnke PH, Springer ING, Wiltfang J et al.: Growth and transplantation of a custom vascularised bone graft in a man. Lancet364,766–769 (2005).
  Google Scholar
• 107  Macchiarini M, Jungebluth P, Go T et al.: Clinical transplantation of a tissue-engineered airway. Lancet372(9655),2023–2030 (2008).
  MedlineGoogle Scholar
• 108  De Bari C, Pitzalis C, Dell’Accio F: Reparative medicine: from tissue engineering to joint surface regeneration. Regen. Med.1(1),59–69 (2006).
  CASGoogle Scholar
• 109  Dell’Accio F, De Bari C, Luyten FP: Molecular markers predictive of the capacity of expanded human articular chondrocytes to form stable cartilage in vivo. Arthritis Rheum.44(7),1608–2619 (2001).▪▪ Proposes an in vivo potency assay for chondrocyte preparations to be used for autologous chondrocyte implantation and links its outcome to molecular markers.
  MedlineGoogle Scholar
• 110  Roberts S, Hollander AP, Caterson B, Menage J, Richardson JB: Matrix turnover in human cartilage repair tissue in autologous chondrocyte implantation. Arthritis Rheum.44,2586–2598 (2001).
  Medline CASGoogle Scholar
• 111  Saris DBF, Vanlauwe J, Victor J et al.: Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. Am. J. Sports Med.36(2),235–246 (2008).
  MedlineGoogle Scholar
• 112  Saris DB, Vanlauwe J, Victor J et al.: Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared with microfracture. Am. J. Sports Med.37(Suppl. 1),10S–19S (2009).
  MedlineGoogle Scholar
• 113  Tyndall A, Walker UA, Cope A et al.: Immunomodulatory properties of mesenchymal stem cells: a review based on an interdisciplinary meeting held at the Kennedy Institute of Rheumatology Division, London, UK, 31 October 2005. Arthritis Res. Ther.9(1),301 (2007).
  MedlineGoogle Scholar
• 114  Wakitani S, Imoto K, Yamamoto T,Saito M, Murata N, Yoneda M: Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cart.10,199–206 (2002).
  Medline CASGoogle Scholar
• 115  De Bari C, Dell’Accio F, Luyten F:Failure of in vitro-differentiated mesenchymal stem cells from the synovial membrane to form ectopic stable cartilage in vivo. Arthritis Rheum.50(1),142–150 (2004).
  Medline CASGoogle Scholar
• 116  Scotti C, Tonnarelli B, Papadimitropoulos A et al.: Recapitulation of endochondral bone formation using human adult mesenchymal stem cells as a paradigm for developmental engineering. Proc. Natl Acad. Sci. USA107(16),7251–7256 (2010).▪ Provides evidence that bone marrow MSCs can recapitulate endochondral ossification morphologically and molecularly.
  Medline CASGoogle Scholar
• 117  Pelttari K, Winter A, Steck E et al.: Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice. Arthritis Rheum.54(10),3254–3266 (2006).
  Medline CASGoogle Scholar
• 118  De Bari C, Dell’Accio F, Karystinou A et al.: A biomarker-based mathematical model to predict bone-formation potency of human synovial and periostoeal mesenchymal stem cells. Arthritis Rheum.58(1),240–250 (2008).
  Medline CASGoogle Scholar
• 119  Sakaguchi Y, Sekiya I, Yagishita K, Muneta T: Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum.52(8),2521–2529 (2005).
  MedlineGoogle Scholar
• 120  Karystinou A, Dell’Accio F, Kurth TB et al.: Distinict mesenchymal progenitor cell subsets in the adult human synovium. Rheumatology48(9),1057–1064 (2009).
  Medline CASGoogle Scholar
• 121  Fickert S, Fiedler J, Brenner RE: Identification of subpopulations with characteristics of mesenchymal progenitor cells from human osteoarthritic cartilage using triple staining cell surface markers. Arthritis Res. Ther.6(5),R422–R432 (2004).
  Medline CASGoogle Scholar
• 122  Trommelmans L, Selling J, Dierickx K: A critical assessment of the directive on tissue engineering of the European Union. Tissue Eng.13(4),667–672 (2007).
  MedlineGoogle Scholar
• 123  Michaux G, Van Passel D: Advancedtherapy medicinal products – the rules are harmonised in Europe. Reg. Affairs J. Pharma18(8),1–10 (2007).
  Google Scholar
• 124  Kent J, Pfeffer N: Regulating the collection and use of fetal stem cells. Br. Med. J.332(7546),866–867 (2006).
  MedlineGoogle Scholar
• 125  Barker M: Stem cells: fast and furious. Nature458(7241),962–965 (2009).
  MedlineGoogle Scholar
• 126  Evangelou E, Loughlin J, Spector TD: Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteosrthritis on chromosome 7q22. Ann. Rheum. Dis.70(2),349–355 (2011).
  Medline CASGoogle Scholar
• 127  Meulenbelt I, Bos SD, Chapman K et al.: Meta-analysis of genes modulating intracellular T3 bio-availability reveal a possible role for the DIO3 gene in osteoarthritis susceptibility. Br. Med. J.70(1),164–167 (2011).
  Google Scholar
• 128  Sambrook PN, MacGregor AJ, Spector TD: Genetic influences on cervical and lumbar disc degeneration: a magnetic resonance imaging study in twins. Arthritis Rheum.42(2),366–372 (1999).
  Medline CASGoogle Scholar
• 129  Videman T, Battié MC, Ripatti S, Gill K, Manninen H, Kaprio J: Determinants of the progression in lumbar degeneration: a 5 year follow-up study of adult male monozygotic twins. Spine31(6),671–678 (2006).
  MedlineGoogle Scholar
• 130  Bajada S, Marshall MJ, Wright KT, Richardson JB, Johnson WEB: Decreased osteogenesis, increased cell senescence and elevated Dickkopf-1 secretion in human fracture non union stromal cells. Bone45,726–735 (2010).
  Google Scholar
• 131  Stenderup K, Justesen J, Clauusen C,Kassem M: Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone33,919–926 (2003).
  MedlineGoogle Scholar
• 132  Murphy JM, Dixon K, Beck S, Fabian D, Feldman A, Barry F: Reduced chondrogenic and adipogenic activity of mesenchymal stem cells from patients with advanced osteoarthritis. Arthritis Rheum.46(3),704–713 (2002).
  MedlineGoogle Scholar
• 133  Røsland GV, Svendsen A, Torsvik A et al.: Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. Cancer Res.69(13),5331–5339 (2009).
  Medline CASGoogle Scholar
• 134  Torsvik A, Røsland GV, Svendsen A et al.: Spontaneous malignant transformation of human mesenchymal stem cells reflects cross-contamination: putting the research field on track – letter. Cancer Res.70(15),6393–6396 (2010).
  Medline CASGoogle Scholar
• 135  Prockop DJ, Brenner H, Fibbe WE et al.: Defining the risks of mesenchymal stromal cell therapy. Cytotherapy12(5),576–578 (2010).
  MedlineGoogle Scholar
• 136  Tarte K, Gaillard J, Lataillade JJ et al.: Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation. Blood115(8),1549–1553 (2010).
  Medline CASGoogle Scholar
• 137  Rubio D, Garcia-Castro J, Martin MC et al.: Spontaneous human stem cell transformation. Cancer Res.68(8),3035–3039 (2005).
  Google Scholar
• 138  Wright K, El Masri W, Osman A, Chowdury J, Johnson WEB: Bone marrow cell therapy for SCI. Stem Cell Rev. (2010) (Epub ahead of print).
  Google Scholar
• 139  Kishk NA, Gabr H, Hamdy S et al.: Case control series of intrathecal autologous bone marrow mesenchymal stem cell therapy for chronic spinal cord injury. Neurorehabil. Neural Repair24(8),702–708 (2010).
  MedlineGoogle Scholar
• 140  Delorme B, Ringe J, Pontikoglou C et al.: Specific lineage-priming of bone marrow mesenchymal stem cells provides the molecular framework for their plasticity. Stem Cells27,1142–1151 (2009).
  Medline CASGoogle Scholar
• 141  Oldershaw RA, Baxter MA, Lowe ET et al.: Directed differentiation of human embryonic stem cells towards chondrocytes. Nat. Biotechnol.28(11),1187–1196 (2010).
  Medline CASGoogle Scholar
• 142  Barker M: Testing times for stem cells. Nature463(7282),719–719 (2010).
  MedlineGoogle Scholar
• 143  Caplan AI: Mesenchymal stem cells: the past, the present, the future. Cartilage1(1),6–9 (2010).
  MedlineGoogle Scholar
• 144  Caplan AI, Bruder SP: Mesenchymal stem cells: building blocks for molecular medicine in the 21st century. Trends Mol. Med.7(6),259–264 (2001).
  Medline CASGoogle Scholar
• 201  Arthritis Care: OA Nation: the most comprehensive UK report of people with osteoarthritis www.arthritiscare.org.uk/@3235/Forhealthprofessionals/OANation
  Google Scholar
• 202  The National Collaborating Centre for Chronic Conditions: Osteoarthritis. National clinical guideline for care and management in adults www.nice.org.uk/nicemedia/pdf/CG59NICEguideline.pdf
  Google Scholar
• 203  European Medicines Agency CAT: Reflection paper on stem cell-based medicinal products www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/03/WC500079932.pdf
  Google Scholar