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Biological Treatment for Osteoarthritis of the Knee: Moving from Bench to Bedside—Current Practical Concepts

      Abstract

      Biological-based therapies for cartilage pathology have gained considerable recognition in the last few decades due to their potential benefits including their minimal invasiveness, capacity for unprecedented healing, and potential for rapid recovery. Consequently, these therapies are likely to have the most noteworthy impact on patients with degenerative joint changes who want to remain active. Currently, the most researched treatments include platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), and cell-based therapies. Although further basic science research and well-designed randomized clinical trials are needed to elucidate the long-term role of these therapies in the treatment of osteoarthritis, there is compelling evidence for their use for certain indications. This article aims to review the existing literature for biological-based treatment options for osteoarthritis, critically assessing the current evidence-based recommendations and identify potential avenues for development.
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      References

        • Hochberg M.C.
        Osteoarthritis: The rheumatologist's perspective.
        HSS J. 2012; 8: 35-36
        • Nuesch E.
        • Dieppe P.
        • Reichenbach S.
        • Williams S.
        • Iff S.
        • Juni P.
        All cause and disease specific mortality in patients with knee or hip osteoarthritis: Population based cohort study.
        Br Med J. 2011; 342: d1165
        • Centers for Disease Control and Prevention
        Trends in strength training—United States, 1998-2004.
        MMWR Morb Mortal Wkly Rep. 2006; 55: 769-772
      1. Centers for Disease Control and Prevention. National Health Interview Survey (NHIS), adult sample. 2012.

        • Mather 3rd, R.C.
        • Koenig L.
        • Kocher M.S.
        • et al.
        Societal and economic impact of anterior cruciate ligament tears.
        J Bone Joint Surg Am. 2013; 95: 1751-1759
        • Murray I.R.
        • Benke M.T.
        • Mandelbaum B.R.
        Management of knee articular cartilage injuries in athletes: Chondroprotection, chondrofacilitation, and resurfacing.
        Knee Surg Sports Traumatol Arthrosc. 2016; 24: 1617-1626
        • Speziali A.
        • Delcogliano M.
        • Tei M.
        • et al.
        Chondropenia: Current concept review.
        Musculoskelet Surg. 2015; 99: 189-200
        • LaPrade R.F.
        • Geeslin A.G.
        • Murray I.R.
        • et al.
        Biologic treatments for sports injuries II think tank-current concepts, future research, and barriers to advancement. Part 1. Biologics overview, ligament injury, tendinopathy.
        Am J Sports Med. 2016; 44: 3270-3283
        • Murray I.R.
        • LaPrade R.F.
        • Musahl V.
        • et al.
        Biologic treatments for sports injuries II think tank-current concepts, future research, and barriers to advancement. Part 2. Rotator cuff.
        Orthop J Sports Med. 2016; 4 (2325967116636586)
        • Zlotnicki J.P.
        • Geeslin A.G.
        • Murray I.R.
        • et al.
        Biologic treatments for sports injuries II think tank-current concepts, future research, and barriers to advancement. Part 3. Articular cartilage.
        Orthop J Sports Med. 2016; 4 (2325967116642433)
        • LaPrade C.M.
        • James E.W.
        • LaPrade R.F.
        • Engebretsen L.
        How should we evaluate outcomes for use of biologics in the knee?.
        J Knee Surg. 2015; 28: 35-44
        • Riboh J.C.
        • Saltzman B.M.
        • Yanke A.B.
        • Fortier L.
        • Cole B.J.
        Effect of leukocyte concentration on the efficacy of platelet-rich plasma in the treatment of knee osteoarthritis.
        Am J Sports Med. 2016; 44: 792-800
        • Filardo G.
        • Di Matteo B.
        • Di Martino A.
        • et al.
        Platelet-rich plasma intra-articular knee injections show no superiority versus viscosupplementation: A randomized controlled trial.
        Am J Sports Med. 2015; 43: 1575-1582
        • Duif C.
        • Vogel T.
        • Topcuoglu F.
        • et al.
        Does intraoperative application of leukocyte-poor platelet-rich plasma during arthroscopy for knee degeneration affect postoperative pain, function and quality of life? A 12-month randomized controlled double-blind trial.
        Arch Orthop Trauma Surg. 2015; 135: 971-977
        • 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: 82-97
        • Kim J.D.
        • Lee G.W.
        • Jung G.H.
        • et al.
        Clinical outcome of autologous bone marrow aspirates concentrate (BMAC) injection in degenerative arthritis of the knee.
        Eur J Orthop Surg Traumatol. 2014; 24: 1505-1511
        • Hauser R.A.
        • Orlofsky A.
        Regenerative injection therapy with whole bone marrow aspirate for degenerative joint disease: A case series.
        Clin Med Insights Arthritis Musculoskelet Disord. 2013; 6: 65-72
        • Fibel K.H.
        • Hillstrom H.J.
        • Halpern B.C.
        State-of-the-art management of knee osteoarthritis.
        World J Clin Cases. 2015; 3: 89-101
        • Vega A.
        • Martin-Ferrero M.A.
        • Del Canto F.
        • et al.
        Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: A randomized controlled trial.
        Transplantation. 2015; 99: 1681-1990
        • Chahla J.
        • Dean C.S.
        • Moatshe G.
        • Pascual-Garrido C.
        • Serra Cruz R.
        • LaPrade R.F.
        Concentrated bone marrow aspirate for the treatment of chondral injuries and osteoarthritis of the knee: A systematic review of outcomes.
        Orthop J Sports Med. 2016; 4 (2325967115625481)
        • Chahla J.
        • LaPrade R.F.
        • Mardones R.
        • et al.
        Biological therapies for cartilage lesions in the hip: A new horizon.
        Orthopedics. 2016; 39: e715-723
        • Kraeutler M.J.
        • Chahla J.
        • LaPrade R.F.
        • Pascual-Garrido C.
        Biologic options for articular cartilage wear (platelet-rich plasma, stem cells, bone marrow aspirate concentrate).
        Clin Sports Med. 2017; 36: 457-468
        • Kraeutler M.J.
        • Mitchell J.J.
        • Chahla J.
        • McCarty E.C.
        • Pascual-Garrido C.
        Intra-articular implantation of mesenchymal stem cells. Part 1. A review of the literature for prevention of postmeniscectomy osteoarthritis.
        Orthop J Sports Med. 2017; 5 (2325967116680815)
        • Chahla J.
        • Cinque M.E.
        • Piuzzi N.S.
        • et al.
        A call for standardization in platelet-rich plasma preparation protocols and composition reporting: A systematic review of the clinical orthopaedic literature.
        J Bone Joint Surg Am. 2017; 99: 1769-1779
        • Moatshe G.
        • Morris E.R.
        • Cinque M.E.
        • et al.
        Biological treatment of the knee with platelet-rich plasma or bone marrow aspirate concentrates.
        Acta Orthop. 2017; 88: 670-674
        • Kingsley C.S.
        Blood coagulation; evidence of an antagonist to factor VI in platelet-rich human plasma.
        Nature. 1954; 173: 723-724
        • Ferrari M.
        • Zia S.
        • Valbonesi M.
        • et al.
        A new technique for hemodilution, preparation of autologous platelet-rich plasma and intraoperative blood salvage in cardiac surgery.
        Int J Artif Organs. 1987; 10: 47-50
        • Zhu Y.
        • Yuan M.
        • Meng H.Y.
        • et al.
        Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: A review.
        Osteoarthritis Cartilage. 2013; 21: 1627-1637
        • Dhillon R.S.
        • Schwarz E.M.
        • Maloney M.D.
        Platelet-rich plasma therapy—future or trend?.
        Arthritis Res Ther. 2012; 14: 219
        • Marx R.E.
        Platelet-rich plasma (PRP): What is PRP and what is not PRP?.
        Implant Dent. 2001; 10: 225-228
        • Rughetti A.
        • Giusti I.
        • D'Ascenzo S.
        • et al.
        Platelet gel-released supernatant modulates the angiogenic capability of human endothelial cells.
        Blood Transfus. 2008; 6: 12-17
        • Fleming B.C.
        • Proffen B.L.
        • Vavken P.
        • Shalvoy M.R.
        • Machan J.T.
        • Murray M.M.
        Increased platelet concentration does not improve functional graft healing in bio-enhanced ACL reconstruction.
        Knee Surg Sports Traumatol Arthrosc. 2015; 23: 1161-1170
      2. LaPrade RF, Goodrich LR, Philipps J, et al. Use of platelet-rich plasma immediately post-injury to improve ligament healing was not successful in an in vivo animal model [published online December 1, 2017]. Am J Sports Med. doi:10.1177/0363546517741135.

        • Melchiorre D.
        • Manetti M.
        • Matucci-Cerinic M.
        Pathophysiology of hemophilic arthropathy.
        J Clin Med. 2017; 6: 63
        • Anitua E.
        • Zalduendo M.
        • Troya M.
        • Padilla S.
        • Orive G.
        Leukocyte inclusion within a platelet rich plasma-derived fibrin scaffold stimulates a more pro-inflammatory environment and alters fibrin properties.
        PLoS One. 2015; 10: e0121713
        • Cieslik-Bielecka A.
        • Bielecki T.
        • Gazdzik T.S.
        • Arendt J.
        • Krol W.
        • Szczepanski T.
        Autologous platelets and leukocytes can improve healing of infected high-energy soft tissue injury.
        Transfus Apher Sci. 2009; 41: 9-12
        • Dragoo J.L.
        • Braun H.J.
        • Durham J.L.
        • et al.
        Comparison of the acute inflammatory response of two commercial platelet-rich plasma systems in healthy rabbit tendons.
        Am J Sports Med. 2012; 40: 1274-1281
        • Hall M.P.
        • Band P.A.
        • Meislin R.J.
        • Jazrawi L.M.
        • Cardone D.A.
        Platelet-rich plasma: Current concepts and application in sports medicine.
        J Am Acad Orthop Surg. 2009; 17: 602-608
        • Wasterlain A.S.
        • Braun H.J.
        • Dragoo J.L.
        Contents and formulations of platelet-rich plasma.
        Oper Tech Orthop. 2012; 22: 33-42
        • Wynn T.A.
        • Vannella K.M.
        Macrophages in tissue repair, regeneration, and fibrosis.
        Immunity. 2016; 44: 450-462
        • Sundman E.A.
        • Cole B.J.
        • Karas V.
        • et al.
        The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis.
        Am J Sports Med. 2014; 42: 35-41
        • Kawase T.
        Platelet-rich plasma and its derivatives as promising bioactive materials for regenerative medicine: Basic principles and concepts underlying recent advances.
        Odontology. 2015; 103: 126-135
        • Cassano J.M.
        • Kennedy J.G.
        • Ross K.A.
        • Fraser E.J.
        • Goodale M.B.
        • Fortier L.A.
        Bone marrow concentrate and platelet-rich plasma differ in cell distribution and interleukin 1 receptor antagonist protein concentration.
        Knee Surg Sports Traumatol Arthrosc. 2018; 26: 333-342
        • Castillo T.N.
        • Pouliot M.A.
        • Kim H.J.
        • Dragoo J.L.
        Comparison of growth factor and platelet concentration from commercial platelet-rich plasma separation systems.
        Am J Sports Med. 2011; 39: 266-271
        • Amable P.R.
        • Carias R.B.
        • Teixeira M.V.
        • et al.
        Platelet-rich plasma preparation for regenerative medicine: Optimization and quantification of cytokines and growth factors.
        Stem Cell Res Ther. 2013; 4: 67
        • Dhurat R.
        • Sukesh M.
        Principles and methods of preparation of platelet-rich plasma: A review and author's perspective.
        J Cutan Aesthet Surg. 2014; 7: 189-197
        • Fontenot R.L.
        • Sink C.A.
        • Werre S.R.
        • Weinstein N.M.
        • Dahlgren L.A.
        Simple tube centrifugation for processing platelet-rich plasma in the horse.
        Can Vet J. 2012; 53: 1266-1272
        • Nagata M.J.
        • Messora M.R.
        • Furlaneto F.A.
        • et al.
        Effectiveness of two methods for preparation of autologous platelet-rich plasma: An experimental study in rabbits.
        Eur J Dent. 2010; 4: 395-402
        • Weibrich G.
        • Kleis W.K.
        • Kunz-Kostomanolakis M.
        • Loos A.H.
        • Wagner W.
        Correlation of platelet concentration in platelet-rich plasma to the extraction method, age, sex, and platelet count of the donor.
        Int J Oral Maxillofac Implants. 2001; 16: 693-699
        • Roh Y.H.
        • Kim W.
        • Park K.U.
        • Oh J.H.
        Cytokine-release kinetics of platelet-rich plasma according to various activation protocols.
        Bone Joint Res. 2016; 5: 37-45
        • Scherer S.S.
        • Tobalem M.
        • Vigato E.
        • et al.
        Nonactivated versus thrombin-activated platelets on wound healing and fibroblast-to-myofibroblast differentiation in vivo and in vitro.
        Plast Reconstr Surg. 2012; 129: 46e-54e
        • Dhillon M.S.
        • Patel S.
        • John R.
        PRP in OA knee—update, current confusions and future options.
        SICOT J. 2017; 3: 27
        • Yin Z.
        • Yang X.
        • Jiang Y.
        • et al.
        Platelet-rich plasma combined with agarose as a bioactive scaffold to enhance cartilage repair: An in vitro study.
        J Biomater Appl. 2014; 28: 1039-1050
        • Kon E.
        • Buda R.
        • Filardo G.
        • et al.
        Platelet-rich plasma: Intra-articular knee injections produced favorable results on degenerative cartilage lesions.
        Knee Surg Sports Traumatol Arthrosc. 2010; 18: 472-479
        • Kon E.
        • Mandelbaum B.
        • Buda R.
        • et al.
        Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: From early degeneration to osteoarthritis.
        Arthroscopy. 2011; 27: 1490-1501
        • Hassan A.S.
        • El-Shafey A.M.
        • Ahmed H.S.
        • Hamed M.S.
        Effectiveness of the intra-articular injection of platelet rich plasma in the treatment of patients with primary knee osteoarthritis.
        Egyptian Rheumatol. 2015; 37: 119-124
        • Joshi Jubert N.
        • Rodriguez L.
        • Reverte-Vinaixa M.M.
        • Navarro A.
        Platelet-rich plasma injections for advanced knee osteoarthritis: A prospective, randomized, double-blinded clinical trial.
        Orthop J Sports Med. 2017; 5 (2325967116689386)
        • Kavadar G.
        • Demircioglu D.T.
        • Celik M.Y.
        • Emre T.Y.
        Effectiveness of platelet-rich plasma in the treatment of moderate knee osteoarthritis: A randomized prospective study.
        J Phys Ther Sci. 2015; 27: 3863-3867
        • Gormeli G.
        • Gormeli C.A.
        • Ataoglu B.
        • Colak C.
        • Aslanturk O.
        • Ertem K.
        Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: A randomized, double-blind, placebo-controlled trial.
        Knee Surg Sports Traumatol Arthrosc. 2017; 25: 958-965
        • Filardo G.
        • Kon E.
        • Buda R.
        • et al.
        Platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis.
        Knee Surg Sports Traumatol Arthrosc. 2011; 19: 528-535
        • Gobbi A.
        • Lad D.
        • Karnatzikos G.
        The effects of repeated intra-articular PRP injections on clinical outcomes of early osteoarthritis of the knee.
        Knee Surg Sports Traumatol Arthrosc. 2015; 23: 2170-2177
        • Hart R.
        • Safi A.
        • Komzak M.
        • Jajtner P.
        • Puskeiler M.
        • Hartova P.
        Platelet-rich plasma in patients with tibiofemoral cartilage degeneration.
        Arch Orthop Trauma Surg. 2013; 133: 1295-1301
        • Anitua E.
        • Sanchez M.
        • De la Fuente M.
        • Zalduendo M.M.
        • Orive G.
        Plasma rich in growth factors (PRGF-Endoret) stimulates tendon and synovial fibroblasts migration and improves the biological properties of hyaluronic acid.
        Knee Surg Sports Traumatol Arthrosc. 2012; 20: 1657-1665
        • Andia I.
        • Abate M.
        Knee osteoarthritis: Hyaluronic acid, platelet-rich plasma or both in association?.
        Expert Opin Biol Ther. 2014; 14: 635-649
        • Chen W.H.
        • Lo W.C.
        • Hsu W.C.
        • et al.
        Synergistic anabolic actions of hyaluronic acid and platelet-rich plasma on cartilage regeneration in osteoarthritis therapy.
        Biomaterials. 2014; 35: 9599-9607
        • Saturveithan C.
        • Premganesh G.
        • Fakhrizzaki S.
        • et al.
        Intra-articular hyaluronic acid (HA) and platelet rich plasma (PRP) injection versus hyaluronic acid (HA) injection alone in patients with grade III and IV knee osteoarthritis (OA): A retrospective study on functional outcome.
        Malays Orthop J. 2016; 10: 35-40
        • 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
        • Fortier L.A.
        • Potter H.G.
        • Rickey E.J.
        • et al.
        Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model.
        J Bone Joint Surg Am. 2010; 92: 1927-1937
        • Simmons P.J.
        • Torok-Storb B.
        Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1.
        Blood. 1991; 78: 55-62
        • Dar A.
        • Goichberg P.
        • Shinder V.
        • et al.
        Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells.
        Nat Immunol. 2005; 6: 1038-1046
        • Dominici M.
        • Le Blanc K.
        • Mueller I.
        • et al.
        Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.
        Cytotherapy. 2006; 8: 315-317
        • Oliver K.S.
        • Bayes M.
        • Crane D.
        • Pathikonda C.
        Clinical outcome of bone marrow concentrate in knee osteoarthritis.
        J Prolother. 2015; 7: e937-946
        • Hernigou P.
        • Homma Y.
        • Flouzat Lachaniette C.H.
        • et al.
        Benefits of small volume and small syringe for bone marrow aspirations of mesenchymal stem cells.
        Int Orthop. 2013; 37: 2279-2287
        • Oliver K.
        • Awan T.
        • Bayes M.
        Single- versus multiple-site harvesting techniques for bone marrow concentrate: Evaluation of aspirate quality and pain.
        Orthop J Sports Med. 2017; 5 (2325967117724398)
        • Shapiro S.A.
        • Kazmerchak S.E.
        • Heckman M.G.
        • Zubair A.C.
        • O'Connor M.I.
        A prospective, single-blind, placebo-controlled trial of bone marrow aspirate concentrate for knee osteoarthritis.
        Am J Sports Med. 2017; 45: 82-90
        • Chahla J.
        • Piuzzi N.S.
        • Mitchell J.J.
        • et al.
        Intra-articular cellular therapy for osteoarthritis and focal cartilage defects of the knee: A systematic review of the literature and study quality analysis.
        J Bone Joint Surg Am. 2016; 98: 1511-1521
        • Kraeutler M.J.
        • Mitchell J.J.
        • Chahla J.
        • McCarty E.C.
        • Pascual-Garrido C.
        Intra-articular implantation of mesenchymal stem cells. Part 2. A review of the literature for meniscal regeneration.
        Orthop J Sports Med. 2017; 5 (2325967116680814)
        • Piuzzi N.S.
        • Chahla J.
        • Schrock J.B.
        • et al.
        Evidence for the use of cell-based therapy for the treatment of osteonecrosis of the femoral head: A systematic review of the literature.
        J Arthroplasty. 2017; 32: 1698-1708
        • Muschler G.F.
        • Midura R.J.
        Connective tissue progenitors: Practical concepts for clinical applications.
        Clin Orthop Relat Res. 2002; : 66-80
        • Potten C.S.
        • Loeffler M.
        Stem cells: Attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt.
        Development. 1990; 110: 1001-1020
        • Wolfstadt J.I.
        • Cole B.J.
        • Ogilvie-Harris D.J.
        • Viswanathan S.
        • Chahal J.
        Current concepts: The role of mesenchymal stem cells in the management of knee osteoarthritis.
        Sports Health. 2015; 7: 38-44
        • Chang Y.H.
        • Liu H.W.
        • Wu K.C.
        • Ding D.C.
        Mesenchymal stem cells and their clinical applications in osteoarthritis.
        Cell Transplant. 2016; 25: 937-950
        • Lietman S.A.
        Induced pluripotent stem cells in cartilage repair.
        World J Orthop. 2016; 7: 149-155
        • Ruetze M.
        • Richter W.
        Adipose-derived stromal cells for osteoarticular repair: Trophic function versus stem cell activity.
        Expert Rev Mol Med. 2014; 16: e9
        • Wu L.
        • Cai X.
        • Zhang S.
        • Karperien M.
        • Lin Y.
        Regeneration of articular cartilage by adipose tissue derived mesenchymal stem cells: Perspectives from stem cell biology and molecular medicine.
        J Cell Physiol. 2013; 228: 938-944
        • 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: 1717-1729
        • LaPrade R.F.
        • Dragoo J.L.
        • Koh J.L.
        • Murray I.R.
        • Geeslin A.G.
        • Chu C.R.
        AAOS research symposium updates and consensus: Biologic treatment of orthopaedic injuries.
        J Am Acad Orthop Surg. 2016; 24: e62-78
      3. McIntyre JA, Jones IA, Han B, Vangsness CT. Intra-articular mesenchymal stem cell therapy for the human joint: A systematic review [published online November 1, 2017]. Am J Sports Med. :doi:10.1177/0363546517735844.

        • Breitbach M.
        • Bostani T.
        • Roell W.
        • et al.
        Potential risks of bone marrow cell transplantation into infarcted hearts.
        Blood. 2007; 110: 1362-1369
        • Geraghty R.J.
        • Capes-Davis A.
        • Davis J.M.
        • et al.
        Guidelines for the use of cell lines in biomedical research.
        Br J Cancer. 2014; 111: 1021-1046
        • Goodrich L.R.
        • Chen A.C.
        • Werpy N.M.
        • et al.
        Addition of mesenchymal stem cells to autologous platelet-enhanced fibrin scaffolds in chondral defects: does it enhance repair?.
        J Bone Joint Surg Am. 2016; 98: 23-34
        • Lee K.B.
        • Wang V.T.
        • Chan Y.H.
        • Hui J.H.
        A novel, minimally-invasive technique of cartilage repair in the human knee using arthroscopic microfracture and injections of mesenchymal stem cells and hyaluronic acid—a prospective comparative study on safety and short-term efficacy.
        Ann Acad Med Singapore. 2012; 41: 511-517
        • Saw K.Y.
        • Anz A.
        • Siew-Yoke Jee C.
        • et al.
        Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: A randomized controlled trial.
        Arthroscopy. 2013; 29: 684-694