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http://dx.doi.org/10.12701/yujm.2020.00157

Current perspectives in stem cell therapies for osteoarthritis of the knee  

Kim, Gi Beom (Department of Orthopedic Surgery, Yeungnam University College of Medicine)
Shon, Oog-Jin (Department of Orthopedic Surgery, Yeungnam University College of Medicine)
Publication Information
Journal of Yeungnam Medical Science / v.37, no.3, 2020 , pp. 149-158 More about this Journal
Abstract
Mesenchymal stem cells (MSCs) are emerging as an attractive option for osteoarthritis (OA) of the knee joint, due to their marked disease-modifying ability and chondrogenic potential. MSCs can be isolated from various organ tissues, such as bone marrow, adipose tissue, synovium, umbilical cord blood, and articular cartilage with similar phenotypic characteristics but different proliferation and differentiation potentials. They can be differentiated into a variety of connective tissues such as bone, adipose tissue, cartilage, intervertebral discs, ligaments, and muscles. Although several studies have reported on the clinical efficacy of MSCs in knee OA, the results lack consistency. Furthermore, there is no consensus regarding the proper cell dosage and application method to achieve the optimal effect of stem cells. Therefore, the purpose of this study is to review the characteristics of various type of stem cells in knee OA, especially MSCs. Moreover, we summarize the clinical issues faced during the application of MSCs.
Keywords
Knee joint; Mesenchymal stem cells; Osteoarthritis; Stem cells;
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1 Freitag J, Bates D, Boyd R, Shah K, Barnard A, Huguenin L, et al. Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy. A review. BMC Musculoskelet Disord 2016;17:230.   DOI
2 Barry F, Murphy M. Mesenchymal stem cells in joint disease and repair. Nat Rev Rheumatol 2013;9:584-94.   DOI
3 Vezina Audette R, Lavoie-Lamoureux A, Lavoie JP, Laverty S. Inflammatory stimuli differentially modulate the transcription of paracrine signaling molecules of equine bone marrow multipotent mesenchymal stromal cells. Osteoarthritis Cartilage 2013;21:1116-24.   DOI
4 Jeong SY, Kim DH, Ha J, Jin HJ, Kwon SJ, Chang JW, et al. Thrombospondin-2 secreted by human umbilical cord blood-derived mesenchymal stem cells promotes chondrogenic differentiation. Stem Cells 2013;31:2136-48.   DOI
5 Vega A, Martin-Ferrero MA, Del Canto F, Alberca M, Garcia V, Munar A, et al. Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: a randomized controlled trial. Transplantation 2015;99:1681-90.   DOI
6 Martin DR, Cox NR, Hathcock TL, Niemeyer GP, Baker HJ. Isolation and characterization of multipotential mesenchymal stem cells from feline bone marrow. Exp Hematol 2002;30:879-86.   DOI
7 Johnson MH, McConnell JM. Lineage allocation and cell polarity during mouse embryogenesis. Semin Cell Dev Biol 2004;15:583-97.   DOI
8 Airenne KJ, Hu YC, Kost TA, Smith RH, Kotin RM, Ono C, et al. Baculovirus: an insect-derived vector for diverse gene transfer applications. Mol Ther 2013;21:739-49.   DOI
9 Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143-7.   DOI
10 Gentile P, Calabrese C, De Angelis B, Pizzicannella J, Kothari A, Garcovich S. Impact of the different preparation methods to obtain human adipose-derived stromal vascular fraction cells (AD-SVFs) and human adipose-derived mesenchymal stem cells (AD-MSCs): enzymatic digestion versus mechanical centrifugation. Int J Mol Sci 2019;20:5471.   DOI
11 Lee WS, Kim HJ, Kim KI, Kim GB, Jin W. Intra-articular injection of autologous adipose tissue-derived mesenchymal stem cells for the treatment of knee osteoarthritis: a phase IIb, randomized, placebo-controlled clinical trial. Stem Cells Transl Med 2019;8:504-11.   DOI
12 Pak J, Chang JJ, Lee JH, Lee SH. Safety reporting on implantation of autologous adipose tissue-derived stem cells with platelet-rich plasma into human articular joints. BMC Musculoskelet Disord 2013;14:337.   DOI
13 Pers YM, Rackwitz L, Ferreira R, Pullig O, Delfour C, Barry F, et al. Adipose mesenchymal stromal cell-based therapy for severe osteoarthritis of the knee: a phase I dose-escalation trial. Stem Cells Transl Med 2016;5:847-56.   DOI
14 Kim YS, Kwon OR, Choi YJ, Suh DS, Heo DB, Koh YG. Comparative matched-pair analysis of the injection versus implantation of mesenchymal stem cells for knee osteoarthritis. Am J Sports Med 2015;43:2738-46.   DOI
15 Filardo G, Madry H, Jelic M, Roffi A, Cucchiarini M, Kon E. Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics. Knee Surg Sports Traumatol Arthrosc 2013;21:1717-29.   DOI
16 Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006;8:315-7.   DOI
17 Zimmerlin L, Donnenberg VS, Pfeifer ME, Meyer EM, Paault B, Rubin JP, et al. Stromal vascular progenitors in adult human adipose tissue. Cytometry A 2010;77:22-30.
18 De Bari C, Dell'Accio F, Tylzanowski P, Luyten FP. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum 2001;44:1928-42.   DOI
19 Guilak F, Estes BT, Diekman BO, Moutos FT, Gimble JM. 2010 Nicolas Andry Award: Multipotent adult stem cells from adipose tissue for musculoskeletal tissue engineering. Clin Orthop Relat Res 2010;468:2530-40.   DOI
20 Trubiani O, Orsini G, Caputi S, Piatelli A. Adult mesenchymal stem cells in dental research: a new approach for tissue engineering. Int J Immunopathol Pharmacol 2006;19:451-60.   DOI
21 Ra JC, Shin IS, Kim SH, Kang SK, Kang BC, Lee HY, et al. Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem Cells Dev 2011;20:1297-308.   DOI
22 Danisovic L, Lesny P, Havlas V, Teyssler P, Syrova Z, Kopani M, et al. Chondrogenic differentiation of human bone marrow and adipose tissue-derived mesenchymal stem cells. J Appl Biomed 2007;5:139-50.   DOI
23 Koga H, Shimaya M, Muneta T, Nimura A, Morito T, Hayashi M, et al. Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Res Ther 2008;10:R84.   DOI
24 Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, et al. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation 2013;95:1535-41.   DOI
25 Sasaki A, Mizuno M, Ozeki N, Katano H, Otabe K, Tsuji K, et al. Canine mesenchymal stem cells from synovium have a higher chondrogenic potential than those from infrapatellar fat pad, adipose tissue, and bone marrow. PLoS One 2018;13:e0202922.   DOI
26 Yokota N, Hattori M, Ohtsuru T, Otsuji M, Lyman S, Shimomura K, et al. Comparative clinical outcomes after intra-articular injection with adipose-derived cultured stem cells or noncultured stromal vascular fraction for the treatment of knee osteoarthritis. Am J Sports Med 2019;47:2577-83.   DOI
27 Fodor PB, Paulseth SG. Adipose derived stromal cell (ADSC) injections for pain management of osteoarthritis in the human knee joint. Aesthet Surg J 2016;36:229-36.   DOI
28 Kubosch EJ, Lang G, Furst D, Kubosch D, Izadpanah K, Rolauffs B, et al. The potential for synovium-derived stem cells in cartilage repair. Curr Stem Cell Res Ther 2018;13:174-84.   DOI
29 Koga H, Muneta T, Ju YJ, Nagase T, Nimura A, Mochizuki T, et al. Synovial stem cells are regionally specified according to local microenvironments after implantation for cartilage regeneration. Stem Cells 2007;25:689-96.   DOI
30 Kurth TB, Dell'accio F, Crouch V, Augello A, Sharpe PT, De Bari C. Functional mesenchymal stem cell niches in adult mouse knee joint synovium in vivo. Arthritis Rheum 2011;63:1289-300.   DOI
31 Shimomura K, Yasui Y, Koizumi K, Chijimatsu R, Hart DA, Yonetani Y, et al. First-in-human pilot study of implantation of a scaffold-free tissue-engineered construct generated from autologous synovial mesenchymal stem cells for repair of knee chondral lesions. Am J Sports Med 2018;46:2384-93.   DOI
32 Klontzas ME, Kenanidis EI, Heliotis M, Tsiridis E, Mantalaris A. Bone and cartilage regeneration with the use of umbilical cord mesenchymal stem cells. Expert Opin Biol Ther 2015;15:1541-52.   DOI
33 Madry H, Gao L, Eichler H, Orth P, Cucchiarini M. Bone marrow aspirate concentrate-enhanced marrow stimulation of chondral defects. Stem Cells Int 2017;2017:1609685.
34 Wong KL, Lee KB, Tai BC, Law P, Lee EH, Hui JH. Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years' follow-up. Arthroscopy 2013;29:2020-8.   DOI
35 Wakitani S, Okabe T, Horibe S, Mitsuoka T, Saito M, Koyama T, et al. Safety of autologous bone marrow-derived mesenchymal stem cell transplantation for cartilage repair in 41 patients with 45 joints followed for up to 11 years and 5 months. J Tissue Eng Regen Med 2011;5:146-50.   DOI
36 Davatchi F, Abdollahi BS, Mohyeddin M, Shahram F, Nikbin B. Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients. Int J Rheum Dis 2011;14:211-5.   DOI
37 Davatchi F, Sadeghi Abdollahi B, Mohyeddin M, Nikbin B. Mesenchymal stem cell therapy for knee osteoarthritis: 5 years follow-up of three patients. Int J Rheum Dis 2016;19:219-25.   DOI
38 Medical Advisory Secretariat. Osteogenic protein-1 for long bone nonunion: an evidence-based analysis. Ont Health Technol Assess Ser 2005;5:1-57.
39 Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006;98:1076-84.   DOI
40 Hernigou P, Mathieu G, Poignard A, Manicom O, Beaujean F, Rouard H. Percutaneous autologous bone-marrow grafting for nonunions: surgical technique. J Bone Joint Surg Am 2006;88(1 Suppl 2):322-7.   DOI
41 Centeno C, Pitts J, Al-Sayegh H, Freeman M. Efficacy of autologous bone marrow concentrate for knee osteoarthritis with and without adipose graft. Biomed Res Int 2014;2014:370621.   DOI
42 Jin HJ, Bae YK, Kim M, Kwon SJ, Jeon HB, Choi SJ, et al. Comparative analysis of human mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord blood as sources of cell therapy. Int J Mol Sci 2013;14:17986-8001.   DOI
43 Park YB, Ha CW, Lee CH, Yoon YC, Park YG. Cartilage regeneration in osteoarthritic patients by a composite of allogeneic umbilical cord blood-derived mesenchymal stem cells and hyaluronate hydrogel: results from a clinical trial for safety and proof-of-concept with 7 years of extended follow-up. Stem Cells Transl Med 2017;6:613-21.   DOI
44 Mithoefer K, McAdams T, Williams RJ, Kreuz PC, Mandelbaum BR. Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am J Sports Med 2009;37:2053-63.   DOI
45 Guler-Yuksel M, Allaart CF, Watt I, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, van Schaardenburg D, et al. Treatment with $TNF-{\alpha}$ inhibitor infliximab might reduce hand osteoarthritis in patients with rheumatoid arthritis. Osteoarthritis Cartilage 2010;18:1256-62.   DOI
46 Hawker GA, Mian S, Bednis K, Stanaitis I. Osteoarthritis year 2010 in review: non-pharmacologic therapy. Osteoarthritis Cartilage 2011;19:366-74.   DOI
47 Goyal D, Keyhani S, Lee EH, Hui JH. Evidence-based status of microfracture technique: a systematic review of level I and II studies. Arthroscopy 2013;29:1579-88.   DOI
48 Niemeyer P, Porichis S, Steinwachs M, Erggelet C, Kreuz PC, Schmal H, et al. Long-term outcomes after first-generation autologous chondrocyte implantation for cartilage defects of the knee. Am J Sports Med 2014;42:150-7.   DOI
49 Martincic D, Radosavljevic D, Drobnic M. Ten-year clinical and radiographic outcomes after autologous chondrocyte implantation of femoral condyles. Knee Surg Sports Traumatol Arthrosc 2014;22:1277-83.   DOI
50 Matas J, Orrego M, Amenabar D, Infante C, Tapia-Limonchi R, Cadiz MI, et al. Umbilical cord-derived mesenchymal stromal cells (MSCs) for knee osteoarthritis: repeated MSC dosing is superior to a single MSC dose and to hyaluronic acid in a controlled randomized Phase I/II trial. Stem Cells Transl Med 2019;8:215-24.   DOI
51 Ha CW, Park YB, Chung JY, Park YG. Cartilage repair using composites of human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel in a minipig model. Stem Cells Transl Med 2015;4:1044-51.   DOI
52 Grigolo B, Lisignoli G, Piacentini A, Fiorini M, Gobbi P, Mazzotti G, et al. Evidence for redifferentiation of human chondrocytes grown on a hyaluronan-based biomaterial (HYAff 11): molecular, immunohistochemical and ultrastructural analysis. Biomaterials 2002;23:1187-95.   DOI
53 Kon E, Verdonk P, Condello V, Delcogliano M, Dhollander A, Filardo G, et al. Matrix-assisted autologous chondrocyte transplantation for the repair of cartilage defects of the knee: systematic clinical data review and study quality analysis. Am J Sports Med 2009;37(Suppl 1):156S-166S.
54 Rai V, Dilisio MF, Dietz NE, Agrawal DK. Recent strategies in cartilage repair: a systemic review of the scaffold development and tissue engineering. J Biomed Mater Res A 2017;105:2343-54.   DOI
55 de Lange-Brokaar BJ, Ioan-Facsinay A, van Osch GJ, Zuurmond AM, Schoones J, Toes RE, et al. Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review. Osteoarthritis Cartilage 2012;20:1484-99.   DOI
56 Gudas R, Gudaite A, Mickevicius T, Masiulis N, Simonaityte R, Cekanauskas E, et al. Comparison of osteochondral autologous transplantation, microfracture, or debridement techniques in articular cartilage lesions associated with anterior cruciate ligament injury: a prospective study with a 3-year follow-up. Arthroscopy 2013;29:89-97.   DOI
57 Jo CH, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC, 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;32:1254-66.   DOI
58 Gupta S, Hawker GA, Laporte A, Croxford R, Coyte PC. The economic burden of disabling hip and knee osteoarthritis (OA) from the perspective of individuals living with this condition. Rheumatology (Oxford) 2005;44:1531-7.   DOI
59 Vincenti MP, Brinckerhoff CE. Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specific transcription factors. Arthritis Res 2002;4:157-64.   DOI
60 Roach HI, Yamada N, Cheung KS, Tilley S, Clarke NM, Oreffo RO, et al. Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions. Arthritis Rheum 2005;52:3110-24.   DOI
61 Martin JA, Buckwalter JA. The role of chondrocyte senescence in the pathogenesis of osteoarthritis and in limiting cartilage repair. J Bone Joint Surg Am 2003;85A(Suppl 2):106-10.   DOI
62 Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, et al. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy 2013;15:641-8.   DOI
63 Chevalier X, Eymard F, Richette P. Biologic agents in osteoarthritis: hopes and disappointments. Nat Rev Rheumatol 2013;9:400-10.   DOI
64 Sampson S, Smith J, Vincent H, Aufiero D, Zall M, Botto-van-Bemden A. Intra-articular bone marrow concentrate injection protocol: short-term efficacy in osteoarthritis. Regen Med 2016;11:511-20.   DOI
65 Shapiro SA, Kazmerchak SE, Heckman MG, Zubair AC, O'Connor MI. A prospective, single-blind, placebo-controlled trial of bone marrow aspirate concentrate for knee osteoarthritis. Am J Sports Med 2017;45:82-90.   DOI
66 Jin YZ, Lee JH. Mesenchymal stem cell therapy for bone regeneration. Clin Orthop Surg 2018;10:271-8.   DOI
67 Raposio E, Bonomini S, Calderazzi F. Isolation of autologous adipose tissue-derived mesenchymal stem cells for bone repair. Orthop Traumatol Surg Res 2016;102:909-12.   DOI
68 Patrikoski M, Juntunen M, Boucher S, Campbell A, Vemuri MC, Mannerstrom B, et al. Development of fully defined xeno-free culture system for the preparation and propagation of cell therapy-compliant human adipose stem cells. Stem Cell Res Ther 2013;4:27.   DOI
69 Thirumala S, Gimble JM, Devireddy RV. Cryopreservation of stromal vascular fraction of adipose tissue in a serum-free freezing medium. J Tissue Eng Regen Med 2010;4:224-32.   DOI
70 Breitbach M, Bostani T, Roell W, Xia Y, Dewald O, Nygren JM, et al. Potential risks of bone marrow cell transplantation into infarcted hearts. Blood 2007;110:1362-9.
71 Park JS, Suryaprakash S, Lao YH, Leong KW. Engineering mesenchymal stem cells for regenerative medicine and drug delivery. Methods 2015;84:3-16.   DOI
72 Baer PC, Geiger H. Adipose-derived mesenchymal stromal/stem cells: tissue localization, characterization, and heterogeneity. Stem Cells Int 2012;2012:812693.   DOI
73 Zhu Y, Wu X, Liang Y, Gu H, Song K, Zou X, et al. Repair of cartilage defects in osteoarthritis rats with induced pluripotent stem cell derived chondrocytes. BMC Biotechnol 2016;16:78.   DOI
74 Miao Q, Shim W, Tee N, Lim SY, Chung YY, Ja KP, et al. iPSC-derived human mesenchymal stem cells improve myocardial strain of infarcted myocardium. J Cell Mol Med 2014;18:1644-54.   DOI
75 Sareen D, Gowing G, Sahabian A, Staggenborg K, Paradis R, Avalos P, et al. Human induced pluripotent stem cells are a novel source of neural progenitor cells (iNPCs) that migrate and integrate in the rodent spinal cord. J Comp Neurol 2014;522:2707-28.   DOI
76 Trokovic R, Weltner J, Nishimura K, Ohtaka M, Nakanishi M, Salomaa V, et al. Advanced feeder-free generation of induced pluripotent stem cells directly from blood cells. Stem Cells Transl Med 2014;3:1402-9.   DOI
77 Lien CY, Chih-Yuan Ho K, Lee OK, Blunn GW, Su Y. Restoration of bone mass and strength in glucocorticoid-treated mice by systemic transplantation of CXCR4 and cbfa-1 co-expressing mesenchymal stem cells. J Bone Miner Res 2009;24:837-48.   DOI
78 Cho SW, Sun HJ, Yang JY, Jung JY, An JH, Cho HY, et al. Transplantation of mesenchymal stem cells overexpressing RANK-Fc or CXCR4 prevents bone loss in ovariectomized mice. Mol Ther 2009;17:1979-87.   DOI