Mesenchymal stem cell therapy for osteoarthritis: current perspectives

Cody C Wyles, Matthew T Houdek, Atta Behfar, Rafael J Sierra, Cody C Wyles, Matthew T Houdek, Atta Behfar, Rafael J Sierra

Abstract

Osteoarthritis (OA) is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs) are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.

Keywords: cell therapy; mesenchymal stem cell; osteoarthritis; regenerative medicine; treatment.

Figures

Figure 1
Figure 1
Techniques for derivation and surgical application of bone marrow- and adipose-derived MSCs. Following extraction of either bone marrow (top row) or adipose tissue (bottom row), MSCs can be isolated and subsequently transplanted (black arrows) to musculoskeletal tissues in need of regeneration. Abbreviation: MSCs, mesenchymal stem cells.

References

    1. Buckwalter JA, Martin JA. Osteoarthritis. Adv Drug Deliv Rev. 2006;58(2):150–167.
    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.
    1. Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am. 2007;89(4):780–785.
    1. Kurtz SM, Lau E, Ong K, Zhao K, Kelly M, Bozic KJ. Future young patient demand for primary and revision joint replacement: national projections from 2010 to 2030. Clin Orthop Relat Res. 2009;467(10):2606–2612.
    1. Hootman JM, Helmick CG. Projections of US prevalence of arthritis and associated activity limitations. Arthritis Rheum. 2006;54(1):226–229.
    1. Yelin E, Murphy L, Cisternas MG, Foreman AJ, Pasta DJ, Helmick CG. Medical care expenditures and earnings losses among persons with arthritis and other rheumatic conditions in 2003, and comparisons with 1997. Arthritis Rheum. 2007;56(5):1397–1407.
    1. Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken) 2012;64(4):465–474.
    1. Bert JM, Gasser SI. Approach to the osteoarthritic knee in the aging athlete: debridement to osteotomy. Arthroscopy. 2002;18(9 Suppl 2):107–110.
    1. Bartlett W, Skinner JA, Gooding CR, et al. Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee: a prospective, randomised study. J Bone Joint Surg Br. 2005;87(5):640–645.
    1. Bentley G, Biant LC, Carrington RW, et al. A prospective, randomised comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee. J Bone Joint Surg Br. 2003;85(2):223–230.
    1. Feczko P, Hangody L, Varga J, et al. Experimental results of donor site filling for autologous osteochondral mosaicplasty. Arthroscopy. 2003;19(7):755–761.
    1. Hangody L, Fules P. Autologous osteochondral mosaicplasty for the treatment of full-thickness defects of weight-bearing joints: ten years of experimental and clinical experience. J Bone Joint Surg Am. 2003;85-A(Suppl 2):25–32.
    1. Henderson I, Francisco R, Oakes B, Cameron J. Autologous chondrocyte implantation for treatment of focal chondral defects of the knee–a clinical, arthroscopic, MRI and histologic evaluation at 2 years. Knee. 2005;12(3):209–216.
    1. Knutsen G, Engebretsen L, Ludvigsen TC, et al. Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J Bone Joint Surg Am. 2004;86-A(3):455–464.
    1. Peterson L, Minas T, Brittberg M, Lindahl A. Treatment of osteochondritis dissecans of the knee with autologous chondrocyte transplantation: results at two to ten years. J Bone Joint Surg Am. 2003;85-A(Suppl 2):17–24.
    1. Sampson S, Botto-van Bemden A, Aufiero D. Stem cell therapies for treatment of cartilage and bone disorders: osteoarthritis, avascular necrosis, and non-union fractures. PM R. 2015;7(4 Suppl):S26–S32.
    1. Kolf CM, Cho E, Tuan RS. Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res Ther. 2007;9(1):204.
    1. Glenn JD, Whartenby KA. Mesenchymal stem cells: emerging mechanisms of immunomodulation and therapy. World J Stem Cells. 2014;6(5):526–539.
    1. Strioga M, Viswanathan S, Darinskas A, Slaby O, Michalek J. Same or not the same? Comparison of adipose tissue-derived versus bone marrow-derived mesenchymal stem and stromal cells. Stem Cells Dev. 2012;21(14):2724–2752.
    1. Ernst E. Complementary or alternative therapies for osteoarthritis. Nat Clin Pract Rheumatol. 2006;2(2):74–80.
    1. Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008;16(2):137–162.
    1. Raynauld JP, Buckland-Wright C, Ward R, et al. Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2003;48(2):370–377.
    1. Celeste C, Ionescu M, Robin Poole A, Laverty S. Repeated intraarticular injections of triamcinolone acetonide alter cartilage matrix metabolism measured by biomarkers in synovial fluid. J Orthop Res. 2005;23(3):602–610.
    1. Nakazawa F, Matsuno H, Yudoh K, Watanabe Y, Katayama R, Kimura T. Corticosteroid treatment induces chondrocyte apoptosis in an experimental arthritis model and in chondrocyte cultures. Clin Exp Rheumatol. 2002;20(6):773–781.
    1. Wyles CC, Houdek MT, Wyles SP, Wagner ER, Behfar A, Sierra RJ. Differential cytotoxicity of corticosteroids on human mesenchymal stem cells. Clin Orthop Relat Res. 2015;473(3):1155–1164.
    1. Rutjes AW, Juni P, da Costa BR, Trelle S, Nuesch E, Reichenbach S. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med. 2012;157(3):180–191.
    1. Bozic KJ, Chiu VW, Slover JD, Immerman I, Kahn JG. Health state utility in patients with osteoarthritis of the hip and total hip arthroplasty. J Arthroplasty. 2011;26(6 Suppl):129–132.e121.
    1. Nwachukwu BU, McLawhorn AS, Simon MS, et al. Management of end-stage ankle arthritis: cost-utility analysis using direct and indirect costs. J Bone Joint Surg Am. 2015;97(14):1159–1172.
    1. Pinkas D, Wiater JM, Spencer EE, Jr, et al. Shoulder prosthetic arthroplasty options in 2014: what to do and when to do it. Instr Course Lect. 2015;64:193–202.
    1. Barry F, Murphy M. Mesenchymal stem cells in joint disease and repair. Nat Rev Rheumatol. 2013;9(10):584–594.
    1. Noth U, Steinert AF, Tuan RS. Technology insight: adult mesenchymal stem cells for osteoarthritis therapy. Nat Clin Pract Rheumatol. 2008;4(7):371–380.
    1. Abu Kasim NH, Govindasamy V, Gnanasegaran N, et al. Unique molecular signatures influencing the biological function and fate of post-natal stem cells isolated from different sources. J Tissue Eng Regen Med. 2012
    1. Gimble J, Guilak F. Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy. 2003;5(5):362–369.
    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(10):845–853.
    1. Liu TM, Martina M, Hutmacher DW, Hui JH, Lee EH, Lim B. Identification of common pathways mediating differentiation of bone marrow- and adipose tissue-derived human mesenchymal stem cells into three mesenchymal lineages. Stem Cells. 2007;25(3):750–760.
    1. Shafiee A, Seyedjafari E, Soleimani M, Ahmadbeigi N, Dinarvand P, Ghaemi N. A comparison between osteogenic differentiation of human unrestricted somatic stem cells and mesenchymal stem cells from bone marrow and adipose tissue. Biotechnol Lett. 2011;33(6):1257–1264.
    1. Stockmann P, Park J, von Wilmowsky C, et al. Guided bone regeneration in pig calvarial bone defects using autologous mesenchymal stem/progenitor cells – a comparison of different tissue sources. J Craniomaxillofac Surg. 2012;40(4):310–320.
    1. Wen Y, Jiang B, Cui J, et al. Superior osteogenic capacity of different mesenchymal stem cells for bone tissue engineering. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;116(5):e324–e332.
    1. Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12):4279–4295.
    1. Murphy JM, Fink DJ, Hunziker EB, Barry FP. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003;48(12):3464–3474.
    1. Horie M, Choi H, Lee RH, et al. 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(10):1197–1207.
    1. 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. 2002;46(3):704–713.
    1. Giannoudis P, Tzioupis C, Almalki T, Buckley R. Fracture healing in osteoporotic fractures: is it really different? A basic science perspective. Injury. 2007;38(Suppl 1):S90–S99.
    1. Hernigou P, Beaujean F. Abnormalities in the bone marrow of the iliac crest in patients who have osteonecrosis secondary to corticosteroid therapy or alcohol abuse. J Bone Joint Surg Am. 1997;79(7):1047–1053.
    1. Lee JS, Roh HL, Kim CH, Jung JS, Suh KT. Alterations in the differentiation ability of mesenchymal stem cells in patients with nontraumatic osteonecrosis of the femoral head: comparative analysis according to the risk factor. J Orthop Res. 2006;24(4):604–609.
    1. Moerman EJ, Teng K, Lipschitz DA, Lecka-Czernik B. Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell. 2004;3(6):379–389.
    1. Wyles CC, Houdek MT, Crespo-Diaz RJ, et al. Adipose-derived mesenchymal stem cells are phenotypically superior for regeneration in the setting of osteonecrosis of the femoral head. Clin Orthop Relat Res. 2015
    1. Al Faqeh H, Nor Hamdan BM, Chen HC, Aminuddin BS, Ruszymah BH. 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(6):458–464.
    1. Diekman BO, Wu CL, Louer CR, et al. Intra-articular delivery of purified mesenchymal stem cells from C57BL/6 or MRL/MpJ superhealer mice prevents posttraumatic arthritis. Cell Transplant. 2013;22(8):1395–1408.
    1. Frisbie DD, Kisiday JD, Kawcak CE, Werpy NM, McIlwraith CW. Evaluation of adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis. J Orthop Res. 2009;27(12):1675–1680.
    1. Guercio A, Di Marco P, Casella S, et al. Production of canine mesenchymal stem cells from adipose tissue and their application in dogs with chronic osteoarthritis of the humeroradial joints. Cell Biol Int. 2012;36(2):189–194.
    1. Sato M, Uchida K, Nakajima H, et al. Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis. Arthritis Res Ther. 2012;14(1):R31.
    1. Toghraie F, Razmkhah M, Gholipour MA, et al. Scaffold-free adipose-derived stem cells (ASCs) improve experimentally induced osteoarthritis in rabbits. Arch Iran Med. 2012;15(8):495–499.
    1. Xia P, Wang X, Lin Q, Li X. Efficacy of mesenchymal stem cells injection for the management of knee osteoarthritis: a systematic review and meta-analysis. Int Orthop. 2015 May 6; Epub.
    1. US National Library of Medicine. [Accessed 2015]. Available from: . NLM identifier: NCT02365142.
    1. US National Library of Medicine. [Accessed 2015]. Available from: . NLM identifier: NCT02237846.
    1. US National Library of Medicine. [Accessed 2015]. Available from: . NLM identifier: NCT01985633.
    1. US National Library of Medicine. [Accessed 2015]. Available from: . NLM identifier: NCT02291926.
    1. US National Library of Medicine. [Accessed 2015]. Available from: . NLM identifier: NCT01895413.
    1. US National Library of Medicine. [Accessed 2015]. Available from: . NLM identifier: NCT01739504.
    1. US National Library of Medicine. [Accessed 2015]. Available from: . NLM identifier: NCT02241408.
    1. US National Library of Medicine. [Accessed 2015]. Available from: . NLM identifier: NCT02118519.
    1. US National Library of Medicine. [Accessed 2015]. Available from: . NLM identifier: NCT01947348.
    1. US National Library of Medicine. [Accessed 2015]. Available from: . NLM identifier: NCT01978639.
    1. US National Library of Medicine. [Accessed 2015]. Available from: . NLM identifier: NCT02351011.
    1. US National Library of Medicine. [Accessed 2015]. Available from: . NLM identifier: NCT01953523.
    1. US National Library of Medicine. [Accessed 2015]. Available from: . NLM identifier: NCT02370823.
    1. US National Library of Medicine. [Accessed 2015]. Available from: . NLM identifier: NCT01733186.
    1. Michalek J, Moster R, Lukac L, et al. Autologous adipose tissue-derived stromal vascular fraction cells application in patients with osteoarthritis. Cell Transplant. 2015 Jan 20; Epub.
    1. Kristjansson B, Honsawek S. Current perspectives in mesenchymal stem cell therapies for osteoarthritis. Stem Cells Int. 2014;2014:194318.
    1. Chang H, Docheva D, Knothe UR, Knothe Tate ML. Arthritic periosteal tissue from joint replacement surgery: a novel, autologous source of stem cells. Stem Cells Transl Med. 2014;3(3):308–317.
    1. Koga H, Muneta T, Ju YJ, et al. Synovial stem cells are regionally specified according to local microenvironments after implantation for cartilage regeneration. Stem Cells. 2007;25(3):689–696.
    1. Liao HT, Chen CT. Osteogenic potential: Comparison between bone marrow and adipose-derived mesenchymal stem cells. World J Stem Cells. 2014;6(3):288–295.
    1. Niemeyer P, Fechner K, Milz S, et al. Comparison of mesenchymal stem cells from bone marrow and adipose tissue for bone regeneration in a critical size defect of the sheep tibia and the influence of platelet-rich plasma. Biomaterials. 2010;31(13):3572–3579.
    1. Vishnubalaji R, Al-Nbaheen M, Kadalmani B, Aldahmash A, Ramesh T. Comparative investigation of the differentiation capability of bone-marrow- and adipose-derived mesenchymal stem cells by qualitative and quantitative analysis. Cell Tissue Res. 2012;347(2):419–427.
    1. Houdek MT, Wyles CC, Martin JR, Sierra RJ. Stem cell treatment for avascular necrosis of the femoral head: current perspectives. Stem Cells Cloning. 2014;7:65–70.
    1. Torre ML, Lucarelli E, Guidi S, et al. Ex vivo expanded mesenchymal stromal cell minimal quality requirements for clinical application. Stem Cells Dev 15. 2015;24(6):677–685.
    1. Bentivegna A, Miloso M, Riva G, et al. DNA Methylation changes during in vitro propagation of human mesenchymal stem cells: implications for their genomic stability? Stem Cells Int. 2013;2013:192425.
    1. Bornes TD, Adesida AB, Jomha NM. Mesenchymal stem cells in the treatment of traumatic articular cartilage defects: a comprehensive review. Arthritis Res Ther. 2014;16(5):432.
    1. Giannini S, Buda R, Battaglia M, et al. One-step repair in talar osteochondral lesions: 4-year clinical results and t2-mapping capability in outcome prediction. Am J Sports Med. 2013;41(3):511–518.
    1. Gobbi A, Chaurasia S, Karnatzikos G, Nakamura N. Matrix-induced autologous chondrocyte implantation versus multipotent stem cells for the treatment of large patellofemoral chondral lesions: a nonrandomized prospective trial. Cartilage. 2015;6(2):82–97.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться