J Knee Surg 2019; 32(01): 002-008
DOI: 10.1055/s-0038-1676069
Special Focus Section
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Biological Effects of Bone Marrow Concentrate in Knee Pathologies

Lisa A. Fortier
1   Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, New York
,
Eric J. Strauss
2   Department of Orthopaedic Surgery, New York University Medical Center, New York, New York
,
David O. Shepard
3   Department of Orthobiologics, Arthrex Inc, Naples, Florida
,
Liliya Becktell
1   Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, New York
,
John G. Kennedy
4   Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, New York
› Author Affiliations
Further Information

Publication History

11 July 2018

15 October 2018

Publication Date:
30 November 2018 (online)

Abstract

With our aging population desiring to remain active, the incidence and costs associated with managing knee pain from both acute injury and symptomatic knee osteoarthritis continue to dramatically increase. Current treatment methods fall short with respect to their ability to improve the intra-articular environment and restore normal joint homeostasis. With increasing basic science and clinical evidence showing efficacy, cell-based therapies such as bone marrow concentrate (BMC) hold promise as a nonsurgical joint preserving treatment approach. BMC has inherent advantages over other treatments commonly used for various knee pathologies because it is a point-of-care orthobiologic product that uniquely and simultaneously delivers growth factors, anti-inflammatory proteins, and mesenchymal stem cells. There is increasing evidence for the use of BMC for repair of focal cartilage defects and for the treatment of generalized knee pain. However, continued high-quality studies are necessary for the clinical utility of BMC to be critically assessed with particular attention paid to appropriate patient selection, standardized aspiration, and processing and reporting of both functional and imaging-based outcomes.

 
  • References

  • 1 Cross M, Smith E, Hoy D. , et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014; 73 (07) 1323-1330
  • 2 Kim J-D, 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
  • 3 Moatshe G, Morris ER, Cinque ME. , et al. Biological treatment of the knee with platelet-rich plasma or bone marrow aspirate concentrates. Acta Orthop 2017; 88 (06) 670-674
  • 4 Ferket BS, Feldman Z, Zhou J, Oei EH, Bierma-Zeinstra SMA, Mazumdar M. Impact of total knee replacement practice: cost effectiveness analysis of data from the osteoarthritis initiative. BMJ 2017; 356: j1131
  • 5 HCUP National Inpatient Sample (NIS) Rockville. MD. http://hcupnet.ahrq.gov/. Published 2012
  • 6 Losina E, Paltiel AD, Weinstein AM. , et al. Lifetime medical costs of knee osteoarthritis management in the United States: impact of extending indications for total knee arthroplasty. Arthritis Care Res (Hoboken) 2015; 67 (02) 203-215
  • 7 Piuzzi NS, Khlopas A, Newman JM. , et al. Bone marrow cellular therapies: novel therapy for knee osteoarthritis. J Knee Surg 2018; 31 (01) 22-26
  • 8 Roos EM, Arden NK. Strategies for the prevention of knee osteoarthritis. Nat Rev Rheumatol 2016; 12 (02) 92-101
  • 9 LaPrade CM, James EW, LaPrade RF, Engebretsen L. How should we evaluate outcomes for use of biologics in the knee?. J Knee Surg 2015; 28 (01) 35-44
  • 10 Zlotnicki JP, Geeslin AG, Murray IR. , 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 (04) 2325967116642433
  • 11 Hermann PC, Huber SL, Herrler T. , et al. Concentration of bone marrow total nucleated cells by a point-of-care device provides a high yield and preserves their functional activity. Cell Transplant 2008; 16 (10) 1059-1069
  • 12 Jäger M, Jelinek EM, Wess KM. , et al. Bone marrow concentrate: a novel strategy for bone defect treatment. Curr Stem Cell Res Ther 2009; 4 (01) 34-43
  • 13 Kolvenbach R, Kreissig C, Cagiannos C, Afifi R, Schmaltz E. Intraoperative adjunctive stem cell treatment in patients with critical limb ischemia using a novel point-of-care device. Ann Vasc Surg 2010; 24 (03) 367-372
  • 14 Ponemone V, Gupta S, Sethi D. , et al. Safety and effectiveness of bone marrow cell concentrate in the treatment of chronic critical limb ischemia utilizing a rapid point-of-care system. Stem Cells Int 2017; 2017: 4137626
  • 15 Garwood ER, Burke CJ, Jazrawi LM, Adler RS. Percutaneous ultrasound-guided musculoskeletal applications of autologous bone marrow aspirate concentrate: Preliminary experience from a single institution. Ultrasound Q 2018; ;(January): 1
  • 16 Gianakos A, Ni A, Zambrana L, Kennedy JG, Lane JM. Bone marrow aspirate concentrate in animal long bone healing: an analysis of basic science evidence. J Orthop Trauma 2016; 30 (01) 1-9
  • 17 Baltzer AW, Moser C, Jansen SA, Krauspe R. Autologous conditioned serum (Orthokine) is an effective treatment for knee osteoarthritis. Osteoarthritis Cartilage 2009; 17 (02) 152-160
  • 18 Centeno CJ, Al-Sayegh H, Bashir J, Goodyear S, Freeman MD. A dose response analysis of a specific bone marrow concentrate treatment protocol for knee osteoarthritis. BMC Musculoskelet Disord 2015; 16 (01) 258
  • 19 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 2018; 26 (01) 333-342
  • 20 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 (08) 2325967117724398
  • 21 Shapiro SA, Arthurs JR. Bone marrow aspiration for regenerative orthopedic intervention: technique with ultrasound guidance for needle placement. Regen Med 2017; 12 (08) 917-928
  • 22 Peters AE, Watts AE. Biopsy needle advancement during bone marrow aspiration increases mesenchymal stem cell concentration. Front Vet Sci 2016; 3: 23
  • 23 Itkin T, Gur-Cohen S, Spencer JA. , et al. Distinct bone marrow blood vessels differentially regulate haematopoiesis. Nature 2016; 532 (7599): 323-328
  • 24 Fox BA, Stephens MM. Treatment of knee osteoarthritis with Orthokine-derived autologous conditioned serum. Expert Rev Clin Immunol 2010; 6 (03) 335-345
  • 25 Auw Yang KG, Raijmakers NJ, van Arkel ER. , et al. Autologous interleukin-1 receptor antagonist improves function and symptoms in osteoarthritis when compared to placebo in a prospective randomized controlled trial. Osteoarthritis Cartilage 2008; 16 (04) 498-505
  • 26 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 (01) 82-90
  • 27 Oliver KS, Alexander RW. Combination of autologous adipose-derived tissue stromal vascular fraction plus high density platelet-rich plasma or bone marrow concentrates in Achilles tendon tears. J Prolotherapy 2013; 5: e895-e912
  • 28 Fortier LA, Barker JU, Strauss EJ, McCarrel TM, Cole BJ. The role of growth factors in cartilage repair. Clin Orthop Relat Res 2011; 469 (10) 2706-2715
  • 29 McCarrel T, Fortier L. Temporal growth factor release from platelet-rich plasma, trehalose lyophilized platelets, and bone marrow aspirate and their effect on tendon and ligament gene expression. J Orthop Res 2009; 27 (08) 1033-1042
  • 30 Cassano JM, Schnabel LV, Goodale MB, Fortier LA. Inflammatory licensed equine MSCs are chondroprotective and exhibit enhanced immunomodulation in an inflammatory environment. Stem Cell Res Ther 2018; 9 (01) 82
  • 31 De Bari C, Roelofs AJ. Stem cell-based therapeutic strategies for cartilage defects and osteoarthritis. Curr Opin Pharmacol 2018; 40: 74-80
  • 32 de Witte SFH, Luk F, Sierra Parraga JM. , et al. Immunomodulation by therapeutic mesenchymal stromal cells (MSC) is triggered through phagocytosis of MSC by monocytic cells. Stem Cells 2018; 36 (04) 602-615
  • 33 Pittenger MF, Mackay AM, Beck SC. , et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284 (5411): 143-147
  • 34 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
  • 35 Zhong W, Sumita Y, Ohba S. , et al. In vivo comparison of the bone regeneration capability of human bone marrow concentrates vs. platelet-rich plasma. PLoS One 2012; 7 (07) e40833
  • 36 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
  • 37 Fortier LA, Potter HG, Rickey EJ. , 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 (10) 1927-1937
  • 38 Chu CR, Fortier LA, Williams A. , et al. Minimally manipulated bone marrow concentrate compared with microfracture treatment of full-thickness chondral defects: a one-year study in an equine model. J Bone Joint Surg Am 2018; 100 (02) 138-146
  • 39 Gobbi A, Karnatzikos G, Sankineani SR. One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee. Am J Sports Med 2014; 42 (03) 648-657
  • 40 Enea D, Cecconi S, Calcagno S, Busilacchi A, Manzotti S, Gigante A. One-step cartilage repair in the knee: collagen-covered microfracture and autologous bone marrow concentrate. A pilot study. Knee 2015; 22 (01) 30-35
  • 41 Gobbi RG, Demange MK, de Ávila LFR. , et al. Patellar tracking after isolated medial patellofemoral ligament reconstruction: dynamic evaluation using computed tomography. Knee Surg Sports Traumatol Arthrosc 2017; 25 (10) 3197-3205
  • 42 Verhaegen J, Clockaerts S, Van Osch GJVM, Somville J, Verdonk P, Mertens P. TruFit plug for repair of osteochondral defects—where is the evidence? Systematic review of literature. Cartilage 2015; 6 (01) 12-19
  • 43 Oladeji LO, Stannard JP, Cook CR. , et al. Effects of autogenous bone marrow aspirate concentrate on radiographic integration of femoral condylar osteochondral allografts. Am J Sports Med 2017; 45 (12) 2797-2803
  • 44 Wang Z, Zhai C, Fei H. , et al. Intraarticular injection autologous platelet-rich plasma and bone marrow concentrate in a goat osteoarthritis model. J Orthop Res 2018;00CB
  • 45 Desando G, Giavaresi G, Cavallo C. , et al. Autologous bone marrow concentrate in a sheep model of osteoarthritis: new perspectives for cartilage and meniscus repair. Tissue Eng Part C Methods 2016; 22 (06) 608-619
  • 46 Saltzman BM, Cvetanovich GL, Nwachukwu BU, Mall NA, Bush-Joseph CA, Bach Jr BR. Economic analyses in anterior cruciate ligament reconstruction: a qualitative and systematic review. Am J Sports Med 2016; 44 (05) 1329-1335
  • 47 Goncars V, Kalnberzs K, Jakobsons E. , et al. Treatment of knee osteoarthritis with bone marrow-derived mononuclear cell injection: 12-month follow-up. Cartilage 2018; ;(January): 1947603517746721
  • 48 Rodriguez-Fontan F, Piuzzi NS, Kraeutler MJ, Pascual-Garrido C. Early clinical outcomes of intra-articular injections of bone marrow aspirate concentrate for the treatment of early osteoarthritis of the hip, and knee: a cohort study. PM R 2018; S1934-1482(18):30288-0
  • 49 Canapp Jr SO, Leasure CS, Cox C, Ibrahim V, Carr BJ. Partial cranial cruciate ligament tears treated with stem cell and platelet-rich plasma combination therapy in 36 dogs: a retrospective study. Front Vet Sci 2016; 3: 112