Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy - a review

Julien Freitag, Dan Bates, Richard Boyd, Kiran Shah, Adele Barnard, Leesa Huguenin, Abi Tenen, Julien Freitag, Dan Bates, Richard Boyd, Kiran Shah, Adele Barnard, Leesa Huguenin, Abi Tenen

Abstract

Osteoarthritis is a leading cause of pain and disability across the world. With an aging population its prevalence is likely to further increase. Current accepted medical treatment strategies are aimed at symptom control rather than disease modification. Surgical options including joint replacement are not without possible significant complications. A growing interest in the area of regenerative medicine, led by an improved understanding of the role of mesenchymal stem cells in tissue homeostasis and repair, has seen recent focused efforts to explore the potential of stem cell therapies in the active management of symptomatic osteoarthritis. Encouragingly, results of pre-clinical and clinical trials have provided initial evidence of efficacy and indicated safety in the therapeutic use of mesenchymal stem cell therapies for the treatment of knee osteoarthritis. This paper explores the pathogenesis of osteoarthritis and how mesenchymal stem cells may play a role in future management strategies of this disabling condition.

Keywords: Knee; Mesenchymal Stem Cells; Osteoarthritis.

References

    1. Bitton R. The economic burden of osteoarthritis. Am J Manag Care. 2009;15(8):230–235.
    1. Fransen M, Bridgett L, March L, et al. The epidemiology of osteoarthritis in Asia. Int J Rheum Dis. 2011;14(2):113–121. doi: 10.1111/j.1756-185X.2011.01608.x.
    1. Brooks PM. Impact of osteoarthritis on individuals and society: how much disability? Social consequences and health economic implications. Curr Opin Rheumatol. 2002;14(5):573–577. doi: 10.1097/00002281-200209000-00017.
    1. Peat G, McCarney R, et al. Knee pain and osteoarthritis in older adults: a review of community burden and current use of primary health care. Ann Rheum Dis. 2001;60(2):91–97. doi: 10.1136/ard.60.2.91.
    1. Gupta S, Hawker GA, et al. The economic burden of disabling hip and knee osteoarthritis (OA) from the perspective of individuals living with this condition. Rheumatology. 2005;44(12):1531–1537. doi: 10.1093/rheumatology/kei049.
    1. Issa S, Sharma L. Epidemiology of osteoarthritis: an update. Curr Rheum Rep. 2006;8(1):7–15. doi: 10.1007/s11926-006-0019-1.
    1. Zhou Q, Yang W, Chen J, et al. Metabolic syndrome meets osteoarthritis. Nat Rev Rheumatol. 2012;8:729–737. doi: 10.1038/nrrheum.2012.135.
    1. Bagga H, Burkhardt D, et al. Long-term effects of intra-articular hyaluronan on synovial fluid in osteoarthritis of the knee. J Rheumatol. 2006;33(5):946–950.
    1. Abraham NS, El-Serag HB, et al. Cyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction and cerebrovascular accident. Aliment Pharmacol Ther. 2007;25(8):913–924. doi: 10.1111/j.1365-2036.2007.03292.x.
    1. Baltzer AW, Moser C, et al. Autologous conditioned serum (Orthokine) is an effective treatment for knee osteoarthritis. Osteoarthritis Cartilage. 2009;17(2):152–160. doi: 10.1016/j.joca.2008.06.014.
    1. Cram P, Lu X, et al. Total knee arthroplasty volume, utilization, and outcomes among Medicare beneficiaries, 1991-2010. JAMA. 2012;308(12):1227–1236. doi: 10.1001/2012.jama.11153.
    1. Knutson K, Robertsson O. Swedish Knee Arthroplasty Registry. Acta Orthop. 2010;81(1):5–7. doi: 10.3109/17453671003667267.
    1. Carr A, Robertsson O, et al. Knee replacement. Lancet. 2012;379:1331–1340. doi: 10.1016/S0140-6736(11)60752-6.
    1. Kurtz S, Ong K, et al. Projections of primary and revision hip and knee arthroplasty in the united sates from 2005 to 2030. J Bone Joint Surg Am. 2007;89(4):780–785. doi: 10.2106/JBJS.F.00222.
    1. Singh JA, Kundukulam J, et al. Early postoperative mortality following joint arthroplasty: a systematic review. J Rheumatol. 2011;38:1507–1513. doi: 10.3899/jrheum.110280.
    1. Wylde V, Hewlett S, et al. Persistent pain after joint replacement: prevalence, sensory qualities, and postoperative determinants. Pain. 2011;152:566–572. doi: 10.1016/j.pain.2010.11.023.
    1. Bourne RB, Chesworth BM, et al. Patient satisfaction after total knee arthroplasty: who is satisfied and who is not? Clin Orthop Relat. 2010;468:57–63. doi: 10.1007/s11999-009-1119-9.
    1. SooHoo N, Lieberman J, et al. Factors predicting complication rates following total knee replacement. J Bone Joint Surg Am. 2006;88(3):480–485. doi: 10.2106/JBJS.E.00629.
    1. Buckwalter JA, Mankin HJ. Articular cartilage. Part II: degeneration and osteoarthritis, repair, regeneration and transplantation. J Bone Joint Surg. 1997;79:612–632.
    1. Farnworth L. Osteochondral defects of the knee. Orthopedics. 2000;23(2):146–157.
    1. Burr DB. Subchondral bone. In: Brandt KD, Lomander S, Doherty M (eds). Osteoarthritis. Oxford: Oxford University Press; 1998. p. 144–56.
    1. Felson DT, Zhang Y. An update on the epidemiology of knee and hip osteoarthritis with a view to prevention. Arthritis Rheum. 1998;41:1343–1355. doi: 10.1002/1529-0131(199808)41:8<1343::AID-ART3>;2-9.
    1. Wells T, Davidson C, et al. Age-related changes in the composition, the molecular stoichiometry and the stability of proteoglycan aggregates extracted from human articular cartilage. Biochem J. 2003;370:69–79. doi: 10.1042/bj20020968.
    1. Chen AC, Temple MM, Ng DM, TeKoppele JM, et al. Induction of advanced glycation end products and alterations of the tensile properties of articular cartilage. Arthritis Rheum. 2002;46:3212–3217. doi: 10.1002/art.10627.
    1. Loeser R. Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix. Osteo Cart. 2009;17:971–979. doi: 10.1016/j.joca.2009.03.002.
    1. Mitchell PG, Magna HA, Reeves LM, et al. Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage. J Clin Invest. 1996;97:761–768. doi: 10.1172/JCI118475.
    1. Goldring MB. Osteoarthritis and cartilage: the role of cytokines. Curr Rheumatol Rep. 2000;2(6):459–465. doi: 10.1007/s11926-000-0021-y.
    1. Sandell LJ, Aigner T. Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis. Arthritis Res. 2001;3:107–113. doi: 10.1186/ar148.
    1. Billinghurst RC, Dahlberg L, Ionescu M, et al. Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage. J Clin Invest. 1997;99:1534–1545. doi: 10.1172/JCI119316.
    1. Ohta S, Imai K, Yamashita K, et al. Expression of matrix metalloproteinase 7 (matrilysin) in human osteoarthritic cartilage. Lab Invest. 1998;78:79–87.
    1. Amin A, Abramson S. The role of nitric oxide in articular cartilage breakdown in osteoarthritis. Curr Opin Rheumatol. 1998;10:263–268. doi: 10.1097/00002281-199805000-00018.
    1. Hashimoto S, Ochs RL, Rosen F, et al. Chondrocyte-derived apoptotic bodies and calcification of articular cartilage. Proc Natl Acad Sci U S A. 1998;95:3094–3099. doi: 10.1073/pnas.95.6.3094.
    1. Lippiello L, Hall D, Mankin HJ. Collagen synthesis in normal and osteoarthritic cartilage. J Clin Invest. 1977;59:593–600. doi: 10.1172/JCI108676.
    1. Eyre D, McDevitt CA, Billingham MEJ, et al. Biosynthesis of collagen and other matrix proteins by articular cartilage in experimental osteoarthritis. Biochem J. 1980;188:823–837. doi: 10.1042/bj1880823.
    1. Collins D, McElligott T. Sulphate (35SO4) uptake by chondrocytes in relation to histological changes in osteoarthritic human articular cartilage. Ann Rheum Dis. 1960;19:318–330. doi: 10.1136/ard.19.4.318.
    1. McDevitt CA, Muir H. Biochemical changes in the cartilage of the knee in experimental and natural osteoarthritis in the dog. J Bone Joint Surg Brit. 1976;58:94–101.
    1. Mankin HJ, Johnson ME, Lippiello L. Biochemical and metabolic abnormalities in articular cartilage from osteoarthritic human hips. III. Distribution and metabolism of amino sugar-containing macromolecules. J Bone Joint Surg Am. 1981;63(1):31–139.
    1. Mitrovic D, Gruson M, Demignon J, et al. Metabolism of human femoral head cartilage in osteoarthrosis and subcapital fracture. Ann Rheum Dis. 1981;40:18–26. doi: 10.1136/ard.40.1.18.
    1. Ryu J, Treadwell BV, Mankin HJ. Biochemical and metabolic abnormalities in normal and osteoarthritic human articular cartilage. Arthritis Rheum. 1984;27:49–57. doi: 10.1002/art.1780270109.
    1. Aigner T, Dudhia J. Phenotypic modulation of chondrocytes as a potential therapeutic target in osteoarthritis: a hypothesis. Ann Rheum Dis. 1997;56:287–291. doi: 10.1136/ard.56.5.287.
    1. Girkontaite I, Frischholz S, Lammi P, et al. Immunolocalization of type X collagen in normal fetal and adult osteoarthritic cartilage with monoclonal antibodies. Matrix Biol. 1996;15:231–238. doi: 10.1016/S0945-053X(96)90114-6.
    1. Barry FP. Mesenchymal stem cell therapy in joint disease. Nov Found Symp. 2003;249:86–89. doi: 10.1002/0470867973.ch7.
    1. Im GI, Shin YW, Lee KB. Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells? Osteoarthritis Cartilage. 2005;13:845–853. doi: 10.1016/j.joca.2005.05.005.
    1. Fahy N, de Vreis-van Melle ML, Lehmann J, et al. Human osteoarthritis synovium impact chondrogenic differentiation of mesencymal stem cells via macrophage polarization state. Osteoarthritis Cartilage. 2014;22(8):1167–1175. doi: 10.1016/j.joca.2014.05.021.
    1. Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol. 2010;6(11):625–635. doi: 10.1038/nrrheum.2010.159.
    1. Murphy JM, Dixon K, Beck S, et al. Reduced chondrogenic and adipogenic activity of mesenchymal stem cells from patients with advanced osteoarthritis. Arthritis Rheum. 2002;46:704–713. doi: 10.1002/art.10118.
    1. Barry F, Murphy M. Mesenchymal stem cells in joint disease and repair. Nat Rev Rheumatol. 2013;9:584–594. doi: 10.1038/nrrheum.2013.109.
    1. Barry FP. Biology and clinical applications of mesenchymal stem cells. Birth Defects Res C Embryo Today. 2003;69:250–256. doi: 10.1002/bdrc.10021.
    1. Abramson SB, Attur M. Developments in the scientific understanding of osteoarthritis. Arhtritis Res Ther. 2009;11(3):227. doi: 10.1186/ar2655.
    1. Pelletier JP, Martel-Pelletier J, Abramson SB. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum. 2001;44:1237–1247. doi: 10.1002/1529-0131(200106)44:6<1237::AID-ART214>;2-F.
    1. Vaananen HK. Mesenchymal stem cells. Ann Med. 2005;37(7):469–479. doi: 10.1080/07853890500371957.
    1. Barry FP, Murphy JM. Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol. 2004;36(4):568–584. doi: 10.1016/j.biocel.2003.11.001.
    1. Arinzeh TL. Mesenchymal stem cells for bone repair: preclinical studies and potential orthopaedic applications. Foot Ankle Clin. 2005;10(4):651–665. doi: 10.1016/j.fcl.2005.06.004.
    1. Noel D, Djouad F, Jorgense C. Regenerative medicine through mesenchymal stem cells for bone and cartilage repair. Curr Opin Investig Drugs. 2002;3(7):1000–1004.
    1. Zhou S, Eid K, Glowacki J. Cooperation between TGF-beta and Wnt pathways during chondrocyte and adipocyte differentiation of human marrow stromal cells. J Bone Miner. 2004;19:463–470. doi: 10.1359/JBMR.0301239.
    1. Longobardi L, O'Rear L, Aakula S, et al. Effect of IGF-I in the chondrogenesis of bone marrow mesenchymal stem cells in the presence or absence of TGF-beta signaling. J Bone Miner. 2006;21:626–636. doi: 10.1359/jbmr.051213.
    1. Bosnakovski D, Mizuno M, Kim G, et al. Isolation and multilineage differentiation of bovine bone marrow mesenchymal stem cells. Cell Tissue Res. 2005;319:243–253. doi: 10.1007/s00441-004-1012-5.
    1. Knippenberg M, Helder MN, Zandieh Doulabi B, et al. Osteogenesis versus chondrogenesis by BMP-2 and BMP-7 in adipose stem cells. Biochem Biophys Res. 2006;342:902–908. doi: 10.1016/j.bbrc.2006.02.052.
    1. Solchaga LA, Temenoff JS, Gao J, et al. Repair of osteochondral defects with hyaluronan- and polyester-based scaffolds. Osteoarthritis Cartilage. 2005;13:297–309. doi: 10.1016/j.joca.2004.12.016.
    1. Caplan A. What are MSCs therapeutic? New data: new insight. J Pathol. 2009;217:318–324. doi: 10.1002/path.2469.
    1. Djouad F, Bouffi C, Ghannam S, et al. Mesenchymal stem cell: innovative therapeutic tools for rheumatic diseases. Nat Rev Rheumatol. 2009;5:392–399. doi: 10.1038/nrrheum.2009.104.
    1. Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011;9(1):11–15. doi: 10.1016/j.stem.2011.06.008.
    1. Nakagami H, Morishita R, et al. Adipose tissue-derived stromal cells as a novel option for regenerative cell therapy. J Atheroscler Thromb. 2006;13(2):77. doi: 10.5551/jat.13.77.
    1. Caplan AI. Mesenchymal stem cells. J Orth Res. 1991;9(5):641–650. doi: 10.1002/jor.1100090504.
    1. Wu L, Leijten JC, Georgi N, et al. Trophic effects of mesenchymal stem cells increase chondrocyte proliferation and matrix formation. Tissue Eng. 2011;17(9-10):1425–1436. doi: 10.1089/ten.tea.2010.0517.
    1. de Windt T, Saris DB, Slaper-Cortenbach IC, et al. Direct cell–cell contact with chondrocytes is a key mechanism in multipotent mesenchymal stromal cell-mediated chondrogenesis. Tissue Eng Part A. 2015;21(19-20):2536–2547. doi: 10.1089/ten.tea.2014.0673.
    1. Caplan AI. Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol. 2007;213:341–347. doi: 10.1002/jcp.21200.
    1. Diekman B, et al. Chondrogenesis of adult stem cells from adipose tissue and bone marrow: induction by growth factors and cartilage matrix. Tissue Eng. 2010;16(2):523–533. doi: 10.1089/ten.tea.2009.0398.
    1. Kern S, Eichler JS, Kluter H, et al. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006;24(5):1294–1301. doi: 10.1634/stemcells.2005-0342.
    1. Lo Surdo J, Bauer SR. Quantitative approaches to detect done and passage differences in adipogenic potential and clonogenicity in human bone marrow derived mesenchymal stem cells. Tissue Eng. 2012;18(11):1–13.
    1. Dominici M, Le Blanc K, et al. Minimal criteria for defining mulipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy. 2006;8:315. doi: 10.1080/14653240600855905.
    1. Peng L, et al. Comparative analysis of mesenchymal stem cells from bone marrow, cartilage, and adipose tissue. Stem Cells Dev. 2008;17(4):761–774. doi: 10.1089/scd.2007.0217.
    1. Alvarez-Viejo M, et al. Quantifying mesenchymal stem cells in the mononuclear cell fraction of bone marrow samples obtained for cell therapy. Trans Proc. 2013;45(1):434–439. doi: 10.1016/j.transproceed.2012.05.091.
    1. Kern S, Eichler H, Stoeve J, et al. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006;24:1294–1301. doi: 10.1634/stemcells.2005-0342.
    1. Lee RH, et al. Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. Cell Physiol Biochem. 2004;14(4-6):311–324. doi: 10.1159/000080341.
    1. Zuk PA, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12):4279–4295. doi: 10.1091/mbc.E02-02-0105.
    1. De Ugarte DA, et al. Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs. 2003;174(3):101–109. doi: 10.1159/000071150.
    1. Baksh D, Yao R, Tuan R. Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells. 2007;25(6):1384–1392. doi: 10.1634/stemcells.2006-0709.
    1. Nekanti U, et al. Long-term expansion and pluripotent marker array analysis of Wharton’s jelly-derived mesenchymal stem cells. Stem Cells Dev. 2010;19(1):117–130. doi: 10.1089/scd.2009.0177.
    1. Subramanian A, et al. Human umbilical cord Wharton’s jelly mesenchymal stem cells do not transform to tumor-associated fibroblasts in the presence of breast and ovarian cancer cells unlike bone marrow mesenchymal stem cells. J Cell Biochem. 2012;113(6):1886–1895. doi: 10.1002/jcb.24057.
    1. Le Blanc K, Tammik C, Rosendahl K, et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol. 2003;31:890–896. doi: 10.1016/S0301-472X(03)00110-3.
    1. Brittberg M, Lindahl A, Nilsson A, et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994;331:889–895. doi: 10.1056/NEJM199410063311401.
    1. Brittberg M, Nilsson A, Lindahl A, et al. Rabbit articular cartilage defects treated with autologous cultured chondrocytes. Clin Orthop Relat Res. 1996;326:270–83. doi: 10.1097/00003086-199605000-00034.
    1. Chiang H, et al. Repair of porcine articular cartilage defect with autologous chondrocyte transplantation. J Orthop Res. 2005;23(3):584–593. doi: 10.1016/j.orthres.2004.11.003.
    1. Rahfoth B, Weisser J, Sternkopf F, et al. Transplantation of allograft chondrocytes embedded in agarose gel into cartilage defects of rabbits. Osteoarthritis Cartilage. 1998;6:50–65. doi: 10.1053/joca.1997.0092.
    1. Peterson L, Minas T, Brittberg M, et al. Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res. 2000;374:212–234. doi: 10.1097/00003086-200005000-00020.
    1. Ahsan T, Lottman LM, Harwood F, et al. Integrative cartilage repair: inhibition by beta-aminopropionitrile. J Orthop Res. 1999;17:850–857. doi: 10.1002/jor.1100170610.
    1. von der Mark K, Gauss V, von der Mark H, et al. Relationship between cell shape and type of collagen synthesized as chondrocytes lose their cartilage phenotype in culture. Nature. 1977;267:531–532. doi: 10.1038/267531a0.
    1. Marlovits S, Hombauer M, Truppe M. Changes in the ratio of type-I and type-II collagen expression during monolayer culture of human chondrocytes. J Bone Joint Surg Br. 2004;86:286–295. doi: 10.1302/0301-620X.86B2.14918.
    1. Roberts S, et al. Autologous chondrocyte implantation for cartilage repair: monitoring its success by magnetic resonance imaging and histology. Arthritis Res Ther. 2003;5(1):60–73. doi: 10.1186/ar613.
    1. Steadman JR, Brigss KK, Rodrigo JJ, et al. Outcomes of microfracture for traumatic chodnral defects of the knee: average 11-year follow-up, arthroscopy. J Arthro Relat Surg. 2003;19(5):477–484. doi: 10.1053/jars.2003.50112.
    1. Jakobsen RB, Engebtretsen L, Slauterbeck JR. An analysis of the quality of cartilage repair studies. J Bone Joint Surg Am. 2005;87(10):2232–2239. doi: 10.2106/JBJS.D.02904.
    1. Magnussen RA, Dunn WR, Carey JL, et al. Treatment of focal articular cartilage defects in the knee: a systematic review. Clin Orthop Relat Res. 2008;466(4):952–962. doi: 10.1007/s11999-007-0097-z.
    1. Hunt S, Sherman O. Arthroscopic treatment of osteochondral lesions of the talus with correlation of outcome scoring systems. J Arthro Rel Surg. 2003;19(4):360–367. doi: 10.1053/jars.2003.50047.
    1. Mithoefer K, McADmas T, Willians RJ, et al. Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: and evidence-based systematic analysis. Am J Sports Med. 2009;37(10):2053–2056. doi: 10.1177/0363546508328414.
    1. Steinwachs MR, Guggi T, Kreuz PC. Marrow stimulation techniques. Injury. 2008;39(1):S26–31. doi: 10.1016/j.injury.2008.01.042.
    1. Hangody L, Füles P. Autologous osteochondral mosaicplasty for the treatment of full-thickness defects of weight-bearing joints. J Bone Joint Surg. 2003;85(2):25–32.
    1. Bodo G, Hangody L, Szabo Z, et al. Arthroscopic autologous osteochondral mosaicplasty for the treatment of subchondral cystic lesion in the medial femoral condyle in a horse. Acta Vet Hung. 2000;48:343–354. doi: 10.1556/AVet.48.2000.3.11.
    1. Wohl G, Goplen G, Ford J, et al. Mechanical integrity of subchondral bone in osteochondral autografts and allografts. Can J Surg. 1998;41:228–233.
    1. Bentley G, Biant LC, Carrington RW. A prospective, randomized comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee. J Bone Joint Surg Br. 2003;85(2):223–230. doi: 10.1302/0301-620X.85B2.13543.
    1. Im GI, Kim DY, Shin JH, et al. Repair of cartilage defect in the rabbit with cultured mesenchymal stem cells from bone marrow. J Bone Joint Surg Br. 2001;83:289–294. doi: 10.1302/0301-620X.83B2.10495.
    1. Grigolo B, Lisignoli G, Desando G, Cavallo C, Marconi E, Tschon M, Giavaresi G, Fini M, Giardino R, et al. Osteoarthritis treated with mesenchymal stem cells on hyaluronan-based scaffold in rabbit. Tissue Eng Part C Methods. 2009;15:647–658. doi: 10.1089/ten.tec.2008.0569.
    1. Cui L, Wu Y, Cen L, et al. Repair of articular cartilage defect in non-weight bearing areas using adipose derived stem cells loaded polyglycolic acid mesh. Biomaterials. 2009;30(14):2683–2693. doi: 10.1016/j.biomaterials.2009.01.045.
    1. Dragoo J, et al. Healing full-thickness cartilage defects using adipose-derived stem cells. Tissue Eng. 2007;13(7):1615–1621. doi: 10.1089/ten.2006.0249.
    1. Wakitani S, Goto T, Pineda SJ, et al. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am. 1994;76:579–592.
    1. Liu Y, Shu XZ, Prestwich GD. Osteochondral defect repair with autologous bone marrow-derived mesenchymal stem cells in an injectable, in situ, cross-linked synthetic extracellular matrix. Tissue Eng. 2006;12:3405–3416. doi: 10.1089/ten.2006.12.3405.
    1. Alfaqeh H, Norhamdan MY, Chua KH, et al. Cell based therapy for osteoarthritis in a sheep model: gross and histological assessment. Med J Malaysia. 2008;63(Suppl A):37–38.
    1. Wakitani S, Imoto K, Yamamoto T, et al. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage. 2002;10:199–206. doi: 10.1053/joca.2001.0504.
    1. Nejadnik H, Hui JH, Feng Choong EP, et al. Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med. 2010;38:1110–1116. doi: 10.1177/0363546509359067.
    1. Johnstone B, Hering TM, Caplan AI, et al. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res. 1998;238:265–272. doi: 10.1006/excr.1997.3858.
    1. Shen G. The role of type X collagen in facilitating and regulating endochondral ossification of articular cartilage. Orthod Craniofac Res. 2005;8(1):11–17. doi: 10.1111/j.1601-6343.2004.00308.x.
    1. van Buul GM, Siebelt M, Leijs MJ, et al. Mesenchymal stem cells reduce pain but no degenerative changes in a mono-iodoacetate rat model of osteoarthritis. J Orthop Res. 2014;32(9):1167–1174. doi: 10.1002/jor.22650.
    1. Murphy JM, Fink DJ, Hunziker EB, et al. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003;48:3464–3474. doi: 10.1002/art.11365.
    1. Lee KB, Hui JH, Song IC, Ardany L, et al. Injectable mesenchymal stem cell therapy for large cartilage defects—a porcine model. Stem Cell. 2007;25:2964–71. doi: 10.1634/stemcells.2006-0311.
    1. Saw KY, Hussin P, Loke SC, et al. Articular cartilage regeneration with autologous marrow aspirate and hyaluronic acid: an experimental study in a goat model. Arthroscopy. 2009;25(12):1391–1400. doi: 10.1016/j.arthro.2009.07.011.
    1. Black L, Gaynor J, Adams C, et al. Effect of intra-articular injection of autologous adipose-derived mesenchymal stem and regenerative cells on clinical signs of chronic osteoarthritis of the elbow joint in dogs. Vet Ther. 2008;9:192–200.
    1. Centeno C, Busse D, Kisiday J, et al. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician. 2008;11(3):343–353.
    1. Centeno C, Kisiday J, Freeman M, et al. Partial regeneration of the human hip via autologous bone marrow nucleated cell transfer: a case study. Pain Physician. 2006;9:253–256.
    1. Centeno C, Schultz J, Cheever M. Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique. Curr Stem Cell. 2011;5(1):81–93. doi: 10.2174/157488810790442796.
    1. Pak J. Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose derived stem cells: a case series. J Med Case Rep. 2001;5:296. doi: 10.1186/1752-1947-5-296.
    1. Kuroda R, Ishida K, et al. Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells. Osteoarthritis Cartilage. 2007;15:226–31. doi: 10.1016/j.joca.2006.08.008.
    1. Emadedin M, Aghdami N, Taghiyar L, et al. Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med. 2012;15(7):422–428.
    1. Saw KY, et al. Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: a randomized controlled trial. Arthroscopy. 2013;29(4):684–694. doi: 10.1016/j.arthro.2012.12.008.
    1. Vangsness CT, Farr J, Boyd J, et al. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy. J Bone Joint Surg. 2014;96(2):90–98. doi: 10.2106/JBJS.M.00058.
    1. Jo CH, Lee YG, Shin WH, et al. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof of concept clinical trial. Stem Cells. 2014;32(5):1254–1266. doi: 10.1002/stem.1634.
    1. Vega A, et al. Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: a randomized controlled trial. Transplantation. 2015;99(8):1681–90. doi: 10.1097/TP.0000000000000678.
    1. Davatchi F, Sadeghi-Abdollahi B, Mohyeddin M, et al. Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients. Int J Rheum Dis. 2011;14(2):211–215. doi: 10.1111/j.1756-185X.2011.01599.x.
    1. ADIPOA Report Summary. CORDIS - European Commission, . [Last Accessed 19 May 2016].
    1. Tucker JD, Ericksen JJ, Goetz LL, et al. Should clinical studies involving “regenerative injection therapy”, strive to incorporate a triad of outcome measures instead of only including clinical outcome measures? Osteoarthritis Cartilage. 2014;22(6):715–717. doi: 10.1016/j.joca.2014.04.005.
    1. Qureshi A, Chaoji V, Maiguel D, et al. Proteomic and phospho-proteomic profile of human platelets in Basal, resting state: insights into integrin signaling. PLoS One. 2009;4:e7627. doi: 10.1371/journal.pone.0007627.
    1. Zhu Y, et al. Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: a review. Osteoarthritis Cartilage. 2013;21(11):1627–1637. doi: 10.1016/j.joca.2013.07.017.
    1. Ng F, et al. PDGF, TGF-β, and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages. Blood. 2008;112(2):295–307. doi: 10.1182/blood-2007-07-103697.
    1. Song QH, et al. TGF- (beta) 1 and FGF-2 mRNA expression during fibroblast wound healing. J Clin Pathol. 2002;55(3):164.
    1. Mifune Y, Matsumoto T, Takayama K, et al. The effect of platelet-rich plasma on the regenerative therapy of muscle derived stem cells for articular cartilage repair. Osteoarthritis Cartilage. 2013;21(1):175–185. doi: 10.1016/j.joca.2012.09.018.
    1. Weiss S, Hennig T, Bock R, et al. Impact of growth factors and PTHrP on early and late chondrogenic differentiation of human mesenchymal stem cells. J Cell Physiol. 2010;223:84–93.
    1. Koh YG, Jo SB, Kwon OR, et al. Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy. 2013;29:1e8. doi: 10.1016/j.arthro.2012.11.017.
    1. Xie X, Wang Y, Zhao C, et al. Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration. Biomaterials. 2012;33:7008e18. doi: 10.1016/j.biomaterials.2012.06.058.
    1. Haleem AM, Singergy AA, Sabry D, et al. The clinical use of human culture-expanded autologous bone marrow mesenchymal stem cells trans- planted on platelet-rich fibrin glue in the treatment of articular cartilage defects: a pilot study and preliminary results. Cartilage. 2010;1:253e61. doi: 10.1177/1947603510366027.
    1. Lee HR, Park KM, Joung YK, Park KD, et al. Platelet-rich plasma loaded hydrogel scaffold enhances chondrogenic differentiation and maturation with up-regulation of CB1 and CB2. J Control Release. 2012;159(3):332–7. doi: 10.1016/j.jconrel.2012.02.008.
    1. Giannini S, Buda R, Cavallo M, et al. Cartilage repair evolution in post-traumatic osteochondral lesions of the talus: from open field autologous chondrocyte to bone-marrow-derived cells transplantation. Injury. 2010;41:1196e203.
    1. Maniwa S, Ochi M, Motomura T, et al. Effects of hyaluronic acid and basic fibroblast growth factor on motility of chondrocytes and synovial cells in culture. Acta Orthop Scand. 2001;72:299–303. doi: 10.1080/00016470152846664.
    1. Matsiko A, et al. Addition of hyaluronic acid improves cellular infiltration and promotes early-stage chondrogenesis in a collagen-based scaffold for cartilage tissue engineering. J Mech Behav Biomed Mater. 2012;11:41–52. doi: 10.1016/j.jmbbm.2011.11.012.
    1. Zhu H, et al. The role of the hyaluronan receptor CD44 in mesenchymal stem cell migration in the extracellular matrix. Stem Cells. 2006;24(4):928–935. doi: 10.1634/stemcells.2005-0186.
    1. Toole BP. Hyaluronan in morphogenesis. Seminars in cell & developmental biology. Academic Press. 2001;12(2):79–87.
    1. Snyder TN, et al. A fibrin/hyaluronic acid hydrogel for the delivery of mesenchymal stem cells and potential for articular cartilage repair. J Biol Eng. 2014;8:10. doi: 10.1186/1754-1611-8-10.
    1. US National Institutes of Health: . . [Accessed June 2015].
    1. Rubio D, Carcia-Castro J, Martin M, et al. Spontaneous human adult stem cell transformation. Cancer Res. 2005;65:3035.
    1. Rubio D, Carcia-Castro J, Martin M, et al. Retraction: Spontaneous human adult stem cell transformation. Cancer Res. 2010;70:6682. doi: 10.1158/0008-5472.CAN-09-4640.
    1. Rosland 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. 2009;69:5531. doi: 10.1158/0008-5472.CAN-08-4630.
    1. Torsvik A, Rosland 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. 2010;70:6393. doi: 10.1158/0008-5472.CAN-10-1305.
    1. Pan Q, Fouraschen SM, de Ruiter PE, et al. Detection of spontaneous tumorigenic transformation during culture expansion of human mesenchymal stromal cell. Exp Biol Med. 2014;239(1):105–115. doi: 10.1177/1535370213506802.
    1. Bernardo M, Zaffaroni N, Novara F, et al. Human bone marrow-derived mesenchymal stem cells do not undergo transformation after long term in vitro culture and do not exhibit telomere maintenance mechanisms. Cancer Res. 2007;67:9142. doi: 10.1158/0008-5472.CAN-06-4690.
    1. Lalu ML, McIntyre L, et al. Safety of cell therapy with mesenchymal stromal cells (safe cell): a systematic review and meta-analysis of clinical trials. PLoS One. 2012;7(10):e47559. doi: 10.1371/journal.pone.0047559.
    1. Peeters CM, Leijs MJ, et al. Safety of intra-articular cell-therapy with culture-expanded stem cells in humans: a systematic literature review. Osteo Cartilage. 2013;21(10):1465–1473. doi: 10.1016/j.joca.2013.06.025.
    1. Bielecki TM, Gazdzik TS, Arendt J, et al. Antibacterial effect of autologous platelet gel enriched with growth factors and other active substances: an in vitro study. J Bone Joint Surg Br. 2007;89:417e20.

Source: PubMed

3
Prenumerera