Bone Marrow Cellular Therapies: Novel Therapy for Knee Osteoarthritis

Abstract

Cellular therapies are emerging as potentially promising treatments for numerous musculoskeletal conditions, such as knee osteoarthritis (OA). As orthopaedic surgeons represent a sizable portion of the providers who deliver these therapies, it is particularly essential for them to understand their fundamental principles. One major principle is to identify the appropriate sources for obtaining these cells, with bone marrow being most common. Therefore, the purpose of this review was to provide an overview of cell-based therapies available for the treatment of knee OA with a focus on bone marrow-derived cellular therapies. Specifically, we discuss (1) bone marrow aspiration technique, (2) processing to bone marrow aspirate concentrate, and (3) the rational and clinical evidence for the use of bone marrow cellular therapies for the treatment of knee OA.

Keywords

cell therapies - knee osteoarthritis - bone marrow cellular therapies - bone marrow

• References

• 1 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 (08) 1717-1729
• 2 Diekman BO, Guilak F. Stem cell-based therapies for osteoarthritis: challenges and opportunities. Curr Opin Rheumatol 2013; 25 (01) 119-126
• 3 Marcucio RS, Nauth A, Giannoudis PV. , et al. Stem Cell Therapies in Orthopaedic Trauma. J Orthop Trauma 2015; 29 (12) (Suppl. 12) S24-S27
• 4 Piuzzi NS, Chahla J, Schrock J. , 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 (05) 1698-1708
• 5 Neogi T. The epidemiology and impact of pain in osteoarthritis. Osteoarthritis Cartilage 2013; 21 (09) 1145-1153
• 6 Felson DT, Nevitt MC. Epidemiologic studies for osteoarthritis: new versus conventional study design approaches. Rheum Dis Clin North Am 2004; 30 (04) 783-797
• 7 Arden N, Nevitt MC. Osteoarthritis: epidemiology. Best Pract Res Clin Rheumatol 2006; 20 (01) 3-25
• 8 Roos EM, Arden NK. Strategies for the prevention of knee osteoarthritis. Nat Rev Rheumatol 2016; 12 (02) 92-101
• 9 Chahla J, Piuzzi NS, Mitchell JJ. , 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
• 10 Amini AR, Laurencin CT, Nukavarapu SP. Bone tissue engineering: recent advances and challenges. Crit Rev Biomed Eng 2012; 40 (05) 363-408
• 11 Muschler GF, Nitto H, Boehm CA, Easley KA. Age- and gender-related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors. J Orthop Res 2001; 19 (01) 117-125
• 12 Muschler GF, Nakamoto C, Griffith LG. Engineering principles of clinical cell-based tissue engineering. J Bone Joint Surg Am 2004; 86-A [phone]
• 13 Muschler GF, Boehm C, Easley K. Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume. J Bone Joint Surg Am 1997; 79 (11) 1699-1709
• 14 Jäger M, Hernigou P, Zilkens C. , et al. Cell therapy in bone healing disorders. Orthop Rev (Pavia) 2010; 2 (02) e20
• 15 Hernigou P, Homma Y, Flouzat-Lachaniette CH, Poignard A, Chevallier N, Rouard H. Cancer risk is not increased in patients treated for orthopaedic diseases with autologous bone marrow cell concentrate. J Bone Joint Surg Am 2013; 95 (24) 2215-2221
• 16 Hernigou P, Desroches A, Queinnec S. , et al. Morbidity of graft harvesting versus bone marrow aspiration in cell regenerative therapy. Int Orthop 2014; 38 (09) 1855-1860
• 17 Pierini M, Di Bella C, Dozza B. , et al. The posterior iliac crest outperforms the anterior iliac crest when obtaining mesenchymal stem cells from bone marrow. J Bone Joint Surg Am 2013; 95 (12) 1101-1107
• 18 Hernigou P, Homma Y, Flouzat Lachaniette CH. , et al. Benefits of small volume and small syringe for bone marrow aspirations of mesenchymal stem cells. Int Orthop 2013; 37 (11) 2279-2287
• 19 Luangphakdy V, Boehm C, Pan H, Herrick J, Zaveri P, Muschler GF. Assessment of Methods for Rapid Intraoperative Concentration and Selection of Marrow-Derived Connective Tissue Progenitors for Bone Regeneration Using the Canine Femoral Multidefect Model. Tissue Eng Part A 2016; 22 (1-2): 17-30
• 20 Cassano JM, Kennedy JG, Ross KA, Fraser EJ, Goodale MB, Fortier LA. Bone marrow concentrate and platelet-rich plasma differ in cell distribution and interleukin 1 receptor antagonist protein concentration. Knee Surg Sports Traumatol Arthrosc 2016;
• 21 Hegde V, Shonuga O, Ellis S. , et al. A prospective comparison of 3 approved systems for autologous bone marrow concentration demonstrated nonequivalency in progenitor cell number and concentration. J Orthop Trauma 2014; 28 (10) 591-598
• 22 Lawrence JS, Bremner JM, Bier F. Osteo-arthrosis. Prevalence in the population and relationship between symptoms and x-ray changes. Ann Rheum Dis 1966; 25 (01) 1-24
• 23 Bryan D, Parvizi J, Austin M. , et al; Workgroup of the American Association of Hip and Knee Surgeons Evidence Based Committee. Obesity and total joint arthroplasty: a literature based review. J Arthroplasty 2013; 28 (05) 714-721
• 24 Sharma L. Osteoarthritis year in review 2015: clinical. Osteoarthritis Cartilage 2016; 24 (01) 36-48
• 25 Arden NK, Leyland KM. Osteoarthritis year 2013 in review: clinical. Osteoarthritis Cartilage 2013; 21 (10) 1409-1413
• 26 Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage 2013; 21 (01) 16-21
• 27 Daghestani HN, Kraus VB. Inflammatory biomarkers in osteoarthritis. Osteoarthritis Cartilage 2015; 23 (11) 1890-1896
• 28 Greene MA, Loeser RF. Aging-related inflammation in osteoarthritis. Osteoarthritis Cartilage 2015; 23 (11) 1966-1971
• 29 Malfait AM. Osteoarthritis year in review 2015: biology. Osteoarthritis Cartilage 2016; 24 (01) 21-26
• 30 Orlowsky EW, Kraus VB. The role of innate immunity in osteoarthritis: when our first line of defense goes on the offensive. J Rheumatol 2015; 42 (03) 363-371
• 31 Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone 2012; 51 (02) 249-257
• 32 Sellam J, Berenbaum F. Is osteoarthritis a metabolic disease?. Joint Bone Spine 2013; 80 (06) 568-573
• 33 Varady NH, Grodzinsky AJ. Osteoarthritis year in review 2015: mechanics. Osteoarthritis Cartilage 2016; 24 (01) 27-35
• 34 Karsdal MA, Michaelis M, Ladel C. , et al. Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future. Osteoarthritis Cartilage 2016; 24 (12) 2013-2021
• 35 Kuyinu EL, Narayanan G, Nair LS, Laurencin CT. Animal models of osteoarthritis: classification, update, and measurement of outcomes. J Orthop Surg 2016; 11 (01) 19
• 36 Evans CH, Kraus VB, Setton LA. Progress in intra-articular therapy. Nat Rev Rheumatol 2014; 10 (01) 11-22
• 37 Karsdal MA, Christiansen C, Ladel C, Henriksen K, Kraus VB, Bay-Jensen AC. Osteoarthritis--a case for personalized health care?. Osteoarthritis Cartilage 2014; 22 (01) 7-16
• 38 Wyatt LA, Moreton BJ, Mapp PI. , et al. Histopathological subgroups in knee osteoarthritis. Osteoarthritis Cartilage 2017; 25 (01) 14-22
• 39 Shapiro SA, Kazmerchak SE, Heckman MG, Zubair AC, O'Connor MIA. A Prospective, Single-Blind, Placebo-Controlled Trial of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis. Am J Sports Med 2017; 45 (01) 82-90
• 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
• 41 Kim JD, Lee GW, Jung GH. , 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 (08) 1505-1511