The number of adults with osteoarthritis in the United States is expected to nearly double from 21.4 million in 2005 to 41.1 million by 2030. As a result, medical costs and associated comorbidity will exponentially increase in the coming decades. In the past decade, mesenchymal stem cells (MSCs) have emerged as a novel treatment for degenerative joint disease.
Evidence Acquisition:
PubMed (from 1990 to 2013) was searched to identify relevant studies. Reference lists of included studies were also reviewed.
Study Design:
Clinical review.
Level of Evidence:
Level 3.
Results:
We identified 9 animal and 7 human studies investigating the use of MSCs in the treatment of osteoarthritis, with varying levels of support for this therapy.
Conclusion:
While MSCs have shown potential for improving function and decreasing inflammation in animal studies, translation to patients is still in question. There is a great deal of heterogeneity in treatment methods. Standardizing the manufacturing and characterization of MSCs will allow for better comparisons.
Al FaqehHNor HamdanBMChenHCAminuddinBSRuszymahBH. The potential of intra-articular injection of chondrogenic-induced bone marrow stem cells to retard the progression of osteoarthritis in a sheep model. Exp Gerontol. 2012;47:458-464.
2.
BarryFMurphyM. Mesenchymal stem cells in joint disease and repair. Nat Rev Rheumatol. 2013;9:584-594.
3.
BellamyNCampbellJRobinsonVGeeTBourneRWellsG. Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006;(2):CD005321.
4.
Ben-DavidUBenvenistyN. The tumorigenicity of human embryonic and induced pluripotent stem cells. Nat Rev Cancer. 2011;11:268-277.
5.
BijlsmaJWBerenbaumFLafeberFP. Osteoarthritis: an update with relevance for clinical practice. Lancet. 2011;377:2115-2126.
6.
BittonR. The economic burden of osteoarthritis. Am J Manag Care. 2009;15(suppl):S230-S235.
7.
BjordalJMKlovningALjunggrenAESlørdalL. Short-term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: a meta-analysis of randomised placebo-controlled trials. Eur J Pain. 2007;11:125-138.
8.
BrouwerRWvan RaaijTMVerhaarJACoeneLNBierma-ZeinstraSM. Brace treatment for osteoarthritis of the knee: a prospective randomized multi-centre trial. Osteoarthritis Cartilage. 2006;14:777-783.
CentenoCJBusseDKisidayJKeohanCFreemanMKarliD. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician. 2008;11:343-353.
11.
CraftAMAhmedNRockelJS. Specification of chondrocytes and cartilage tissues from embryonic stem cells. Development. 2013;140:2597-2610.
12.
DavatchiFAbdollahiBSMohyeddinMShahramFNikbinB. Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients. Int J Rheum Dis. 2011;14:211-215.
13.
DiekmanBOWuCLLouerCR. Intra-articular delivery of purified mesenchymal stem cells from C57BL/6 or MRL/MpJ superhealer mice prevents posttraumatic arthritis. Cell Transplant. 2013;22:1395-1408.
14.
EmadedinMAghdamiNTaghiyarL. Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med. 2012;15:422-428.
15.
FakhariABerklandC. Applications and emerging trends of hyaluronic acid in tissue engineering, as a dermal filler and in osteoarthritis treatment. Acta Biomater. 2013;9:7081-7092.
16.
FilardoGMadryHJelicMRoffiACucchiariniMKonE. Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics. Knee Surg Sports Traumatol Arthrosc. 2013;21:1717-1729.
17.
FrisbieDDKisidayJDKawcakCEWerpyNMMcIlwraithCW. Evaluation of adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis. J Orthop Res. 2009;27:1675-1680.
18.
HallMPBandPAMeislinRJJazrawiLMCardoneDA. Platelet-rich plasma: current concepts and application in sports medicine. J Am Acad Orthop Surg. 2009;17:602-608.
19.
HorieMChoiHLeeRH. Intra-articular injection of human mesenchymal stem cells (MSCs) promote rat meniscal regeneration by being activated to express Indian hedgehog that enhances expression of type II collagen. Osteoarthritis Cartilage. 2012;20:1197-1207.
20.
HunterDJ. Osteoarthritis. Best Pract Res Clin Rheumatol. 2011;25:801-814.
21.
JonesEEnglishAChurchmanSM. Large-scale extraction and characterization of CD271+ multipotential stromal cells from trabecular bone in health and osteoarthritis: implications for bone regeneration strategies based on uncultured or minimally cultured multipotential stromal cells. Arthritis Rheum. 2010;62:1944-1954.
22.
JüniPRutjesAWda CostaBRReichenbachS. Viscosupplementation for osteoarthritis of the knee. Ann Intern Med. 2013;158:75.
23.
KhoshbinALerouxTWassersteinD. The efficacy of platelet-rich plasma in the treatment of symptomatic knee osteoarthritis: a systematic review with quantitative synthesis. Arthroscopy. 2013;29:2037-2048.
24.
KirkleyABirminghamTBLitchfieldRB. A randomized trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2008;359:1097-1107.
25.
KirkleyAWebster-BogaertSLitchfieldR. The effect of bracing on varus gonarthrosis. J Bone Joint Surg Am. 1999;81:539-548.
26.
KnoepflerPS. Deconstructing stem cell tumorigenicity: a roadmap to safe regenerative medicine. Stem Cells. 2009;27:1050-1056.
KonEFilardoGDrobnicM. Non-surgical management of early knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2012;20:436-449.
30.
KrügerJPHondkeSEndresMPrussASiclariAKapsC. Human platelet-rich plasma stimulates migration and chondrogenic differentiation of human subchondral progenitor cells. J Orthop Res. 2012;30:845-852.
LoGHLaValleyMMcAlindonTFelsonDT. Intra-articular hyaluronic acid in treatment of knee osteoarthritis: a meta-analysis. JAMA. 2003;290:3115-3121.
33.
MazzoccaADMcCarthyMBIntraviaJ. An in vitro evaluation of the anti-inflammatory effects of platelet-rich plasma, ketorolac, and methylprednisolone. Arthroscopy. 2013;29:675-683.
34.
MichaelJWSchlüter-BrustKUEyselP. The epidemiology, etiology, diagnosis, and treatment of osteoarthritis of the knee. Dtsch Arztebl Int. 2010;107:152-162 [erratum Dtsch Arztebl Int. 2010;107:294].
35.
MoseleyJBO’MalleyKPetersenNJ. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2002;347:81-88.
36.
MurphyJMFinkDJHunzikerEBBarryFP. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003;48:3464-3474.
37.
NakajimaMWakitaniSHaradaYTanigamiATomitaN. In vivo mechanical condition plays an important role for appearance of cartilage tissue in ES cell transplanted joint. J Orthop Res. 2008;26:10-17.
38.
OldershawRA. Cell sources for the regeneration of articular cartilage: the past, the horizon and the future. Int J Exp Pathol. 2012;93:389-400.
39.
OrozcoLMunarASolerR. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation. 2013;95:1535-1541.
40.
PastidesPChimutengwende-GordonMMaffulliNKhanW. Stem cell therapy for human cartilage defects: a systematic review. Osteoarthritis Cartilage. 2013;21:646-654.
41.
PatelSDhillonMSAggarwalSMarwahaNJainA. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013;41:356-364.
42.
PeetersCMLeijsMJReijmanMvan OschGJBosPK. Safety of intra-articular cell-therapy with culture-expanded stem cells in humans: a systematic literature review. Osteoarthritis Cartilage. 2013;86:1465-1473.
43.
ProckopDJBrennerMFibbeWE. Defining the risks of mesenchymal stromal cell therapy. Cytotherapy. 2010;12:576-578.
44.
ProckopDJKeatingA. Relearning the lessons of genomic stability of human cells during expansion in culture: implications for clinical research. Stem Cells. 2012;30:1051-1052.
45.
SakaguchiYSekiyaIYagishitaKMunetaT. Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum. 2005;52:2521-2529.
46.
SatoMUchidaKNakajimaH. Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis. Arthritis Res Ther. 2012;14:R31.
SeshadriVCoyleCHChuCR. Lidocaine potentiates the chondrotoxicity of methylprednisolone. Arthroscopy. 2009;25:337-347.
49.
SpakováTRosochaJLackoMHarvanováDGharaibehA. Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. Am J Phys Med Rehabil. 2012;91:411-417.
50.
TangQOCarascoCFGamieZKorresNMantalarisATsiridisE. Preclinical and clinical data for the use of mesenchymal stem cells in articular cartilage tissue engineering. Expert Opin Biol Ther. 2012;12:1361-1382.
51.
TarteKGaillardJLatailladeJJ. Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation. Blood. 2010;115:1549-1553.
52.
ter HuurneMSchelbergenRBlattesR. Antiinflammatory and chondroprotective effects of intra-articular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum. 2012;64:3604-3613.
53.
ThomasJTSchneiderBSFrankELKrizanSJ. Cartilage repair and replacement in the knee: a regulatory perspective. Trends Biotechnol. 2013;31:665-667.
VeronesiFGiavaresiGTschonMBorsariVNicoli AldiniNFiniM. Clinical use of bone marrow, bone marrow concentrate, and expanded bone marrow mesenchymal stem cells in cartilage disease. Stem Cells Dev. 2013;22:181-192.
58.
WakitaniSAokiHHaradaY. Embryonic stem cells form articular cartilage, not teratomas, in osteochondral defects of rat joints. Cell Transplant. 2004;13:331-336.
59.
WakitaniSGotoTPinedaSJ. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am. 1994;76:579-592.
60.
WakitaniSImotoKYamamotoTSaitoMMurataNYonedaM. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage. 2002;10:199-206.
61.
WakitaniSTakaokaKHattoriT. Embryonic stem cells injected into the mouse knee joint form teratomas and subsequently destroy the joint. Rheumatology (Oxford). 2003;42:162-165.
62.
WatermanRSTomchuckSLHenkleSLBetancourtAM. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an immunosuppressive MSC2 phenotype. PLoS One. 2010;5:e10088.
63.
YoshimuraHMunetaTNimuraAYokoyamaAKogaHSekiyaI. Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle. Cell Tissue Res. 2007;327:449-462.
64.
ZhangWNukiGMoskowitzRW. OARSI recommendations for the management of hip and knee osteoarthritis: part III. Changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage. 2010;18:476-499.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
