The Basic Science of Bone Marrow Aspirate Concentrate in Chondral Injuries

James Holton, Mohamed Imam, Jonathan Ward, Martyn Snow, James Holton, Mohamed Imam, Jonathan Ward, Martyn Snow

Abstract

There has been great interest in bone marrow aspirate concentrate (BMAC) as a cost effective method in delivering mesenchymal stem cells (MSCs) to aid in the repair and regeneration of cartilage defects. Alongside MSCs, BMAC contains a range of growth factors and cytokines to support cell growth following injury. However, there is paucity of information relating to the basic science underlying BMAC and its exact biological role in supporting the growth and regeneration of chondrocytes. The focus of this review is the basic science underlying BMAC in relation to chondral damage and regeneration.

Keywords: Bone; aspirate; cartilage; concentrate; marrow.

Conflict of interest statement

the authors declare no potential conflict of interest.

References

    1. 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;8:315-7.
    1. Xie A, Nie L, Shen G, et al. The application of autologous plateletrich plasma gel in cartilage regeneration. Mol Med Rep 2014;10:1642-8.
    1. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143-7.
    1. Delorme B, Charbord P. Culture and characterization of human bone marrow mesenchymal stem cells. Methods Mol Med 2007;140.
    1. Al Faqeh H, Nor Hamdan BMY, Chen HC, et al. 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;47:458-64.
    1. Pelttari K, Steck E, Richter W. The use of mesenchymal stem cells for chondrogenesis. Injury 2008;39:S58-65.
    1. Im GI, Kim DY, Shin JH, et al. Repair of cartilage defect in the rabbit with cultured mesenchymal stem cells from bone marrow. J Bone Joint Surg Br 2001;83:289-94.
    1. McIlwraith CW, Frisbie DD, Rodkey WG, et al. Evaluation of intra-articular mesenchymal stem cells to augment healing of microfractured chondral defects. Arthroscopy 2011;27:1552-61.
    1. Jung M, Kaszap B, Redohl A, et al. Enhanced early tissue regeneration after matrix-assisted autologous mesenchymal stem cell transplantation in full thickness chondral defects in a minipig model. Cell Transplant 2009;18:923-32.
    1. Gobbi A, Karnatzikos G, Scotti C, et al. One-step cartilage repair with bone marrow aspirate concentrated cells and collagen matrix in full-thickness knee cartilage lesions: results at 2-year follow-up. Cartilage 2011;2:286-99.
    1. 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;24:1505-11.
    1. Hendrich C, Franz E, Waertel G, et al. Safety of autologous bone marrow aspiration concentrate transplantation: initial experiences in 101 patients. Orthop Rev 2009;1:e32.
    1. Bain BJ. The bone marrow aspirate of healthy subjects. Br J Haematol 1996;94: 206-9.
    1. Yamamura R, Yamane T, Hino M, et al. Possible automatic cell classification of bone marrow aspirate using the CELLDYN 4000 automatic blood cell analyzer. J Clin Lab Anal 2002;16:86-90.
    1. Kim M, Kim J, Lim J, et al. Use of an automated hematology analyzer and flow cytometry to assess bone marrow cellularity and differential cell count. Ann Clin Lab Sci 2004;34:307-13.
    1. Cassano JM, Kennedy JG, Ross KA, et al. Bone marrow concentrate and platelet-rich plasma differ in cell distribution and interleukin 1 receptor antagonist protein concentration. Knee Surg Sports Traumatol Arthrosc 2016. [Epub ahead of print]
    1. Oh JH, Kim W, Park KU, Roh YH. Comparison of the cellular composition and cytokine-release kinetics of various platelet-rich plasma preparations. Am J Sports Med 2015;43:3062-70.
    1. Barakat AF, Elson CJ, Westacott CI. Susceptibility to physiological concentrations of IL-1beta varies in cartilage at different anatomical locations on human osteoarthritic knee joints. Osteoarthritis Cartilage 2002;10:264-9.
    1. Jacques C, Gosset M, Berenbaum F, Gabay C. The role of IL-1 and IL-1Ra in joint inflammation and cartilage degradation. Vitam Horm 2006;74:371-403.
    1. Abramson SB, Amin A. Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage. Rheumatol Oxf Engl 2002;41:972-80.
    1. Pelletier JP, Caron JP, Evans C, et al. In vivo suppression of early experimental osteoarthritis by interleukin-1 receptor antagonist using gene therapy. Arthritis Rheum 1997;40:1012-9.
    1. Fernandes JC, Martel-Pelletier J, Pelletier J-P. The role of cytokines in osteoarthritis pathophysiology. Biorheology 2002;39:237-46.
    1. Lotz M, Terkeltaub R, Villiger PM. Cartilage and joint inflammation. Regulation of IL-8 expression by human articular chondrocytes. J Immunol 1992;148:466-73.
    1. Chauffier K, Laiguillon M-C, Bougault C, et al. Induction of the chemokine IL-8/Kc by the articular cartilage: possible influence on osteoarthritis. Joint Bone Spine 2012;79:604-9.
    1. Hou Y, Ryu CH, Jun JA, et al. IL-8 enhances the angiogenic potential of human bone marrow mesenchymal stem cells by increasing vascular endothelial growth factor. Cell Biol Int 2014;38:1050-9.
    1. Sophia Fox AJ, Bedi A, Rodeo SA. The basic science of articular cartilage: structure, composition, and function. Sports Health 2009;1:461-8.
    1. Shukunami C, Oshima Y, Hiraki Y. Chondromodulin-I and tenomodulin: a new class of tissue-specific angiogenesis inhibitors found in hypovascular connective tissues. Biochem Biophys Res Commun 2005;333:299-307.
    1. Moses MA, Wiederschain D, Wu I, et al. Troponin I is present in human cartilage and inhibits angiogenesis. Proc Natl Acad Sci USA 1999;96:2645-50.
    1. Murata M, Yudoh K, Nakamura H, et al. Distinct signaling pathways are involved in hypoxia- and IL-1-induced VEGF expression in human articular chondrocytes. J Orthop Res 2006;24:1544-54.
    1. Maes C, Stockmans I, Moermans K, et al. Soluble VEGF isoforms are essential for establishing epiphyseal vascularization and regulating chondrocyte development and survival. J Clin Invest 2004;113:188-99.
    1. Lund-Olesen K. Oxygen tension in synovial fluids. Arthritis Rheum 1970;13:769-76.
    1. Fortier LA, Barker JU, Strauss EJ, et al. The role of growth factors in cartilage repair. Clin Orthop 2011;469:2706-15.
    1. Miyazawa K, Shinozaki M, Hara T, et al. Two major Smad pathways in TGF-beta superfamily signalling. Genes Cells 2002;7:1191-204.
    1. Kawabata M, Miyazono K. Signal transduction of the TGF-beta superfamily by Smad proteins. J Biochem (Tokyo) 1999;125:9-16.
    1. Zhen G, Cao X. Targeting TGFbeta signaling in subchondral bone and articular cartilage homeostasis. Trends Pharmacol Sci 2014;35:227-36.
    1. Wang W-G, Lou S-Q, Ju X-D, et al. In vitro chondrogenesis of human bone marrow-derived mesenchymal progenitor cells in monolayer culture: activation by transfection with TGF-beta2. Tissue Cell 2003;35:69-77.
    1. Zhao L, Hantash BM. TGF-beta1 regulates differentiation of bone marrow mesenchymal stem cells. Vitam Horm 2011;87:127-41.
    1. Diao H, Wang J, Shen C, et al. Improved cartilage regeneration utilizing mesenchymal stem cells in TGF-beta1 gene-activated scaffolds. Tissue Eng Part A 2009;15:2687-98.
    1. Bakker AC, van de Loo FA, van Beuningen HM, et al. Overexpression of active TGF-beta-1 in the murine knee joint: evidence for synovial-layer-dependent chondroosteophyte formation. Osteoarthritis Cartilage 2001;9:128-36.
    1. Joyce ME, Roberts AB, Sporn MB, Bolander ME. Transforming growth factor-beta and the initiation of chondrogenesis and osteogenesis in the rat femur. J Cell Biol 1990;110:2195-207.
    1. Tekari A, Luginbuhl R, Hofsetter W, Egil RJ. Transforming growth factor beta signaling is essential for the autonomous formation of cartilage-like tissue by expanded chondrocytes. PLoS One 2015;10:e0120857.
    1. Villiger PM, Lotz M. Differential expression of TGF beta isoforms by human articular chondrocytes in response to growth factors. J Cell Physiol 1992;151:318-25.
    1. Fan H, Zhang C, Li J, et al. Gelatin microspheres containing TGF-beta3 enhance the chondrogenesis of mesenchymal stem cells in modified pellet culture. Biomacromolecules 2008;9:927-34.
    1. Tang QO, Shakib K, Heliotis M, et al. TGF-beta3: a potential biological therapy for enhancing chondrogenesis. Expert Opin Biol Ther 2009;9:689-701.
    1. Zhou N, Li Q, Lin X, et al. BMP2 induces chondrogenic differentiation, osteogenic differentiation and endochondral ossification in stem cells. Cell Tissue Res. 2016. [Epub ahead of print]
    1. Schmitt B, Ringe J, Haupl T, et al. BMP2 initiates chondrogenic lineage development of adult human mesenchymal stem cells in high-density culture. Differ Res Biol Divers 2003;71:567-77.
    1. Chubinskaya S, Kumar B, Merrihew C, et al. Age-related changes in cartilage endogenous osteogenic protein-1 (OP-1). Biochim Biophys Acta 2002;1588:126-34.
    1. Jung MR, Shim IK, Chung HJ, et al. Local BMP-7 release from a PLGA scaffolding-matrix for the repair of osteochondral defects in rabbits. J Control Release 2012;162:485-91.
    1. Civinini R, Nistri L, Martini C, et al. Growth factors in the treatment of early osteoarthritis. Clin Cases Miner Bone Metab 2013;10:26-9.
    1. Ataliotis P. Platelet-derived growth factor A modulates limb chondrogenesis both in vivo and in vitro. Mech Dev 2000;94:13-24.
    1. Montaseri A, Busch F, Mobasheri A, et al. IGF-1 and PDGF-bb suppress IL-1beta-induced cartilage degradation through down-regulation of NF-kappaB signaling: involvement of Src/PI-3K/AKT pathway. PloS One 2011;6:e28663.
    1. Li A, Xia X, Yeh J, et al. PDGF-AA promotes osteogenic differentiation and migration of mesenchymal stem cell by down-regulating PDGFRalpha and derepressing BMP-Smad1/5/8 signaling. PloS One 2014;9:e113785.
    1. Fortier LA, Mohammed HO, Lust G, Nixon AJ. Insulin-like growth factor-I enhances cell-based repair of articular cartilage. J Bone Joint Surg Br 2002;84:276-88.
    1. Fortier LA, Balkman CE, Sandell LJ, et al. Insulin-like growth factor-I gene expression patterns during spontaneous repair of acute articular cartilage injury. J Orthop Res 2001;19:720-8.
    1. Pasold J, Zander K, Heskamp B, et al. Positive impact of IGF-1-coupled nanoparticles on the differentiation potential of human chondrocytes cultured on collagen scaffolds. Int J Nanomedicine 2015;10:1131-43.
    1. Mullen LM, Best SM, Ghose S, et al. Bioactive IGF-1 release from collagen-GAG scaffold to enhance cartilage repair in vitro. J Mater Sci Mater Med 2015;26:5325.
    1. Ellman MB, An HS, Muddasani P, Im H-J. Biological impact of the fibroblast growth factor family on articular cartilage and intervertebral disc homeostasis. Gene 2008;420:82-9.
    1. Davidson D, Blanc A, Filion D, et al. Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis. J Biol Chem 2005;280:20509-15.
    1. Reinhold MI, Abe M, Kapadia RM, et al. FGF18 represses noggin expression and is induced by calcineurin. J Biol Chem 2004;279:38209-19.
    1. Moore EE, Bendele AM, Thompson DL, et al. Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis. Osteoarthritis Cartilage 2005;13:623-31.
    1. Correa D, Somoza RA, Lin P, et al. Sequential exposure to fibroblast growth factors (FGF) 2, 9 and 18 enhances hMSC chondrogenic differentiation. Osteoarthritis Cartilage 2015;23:443-53.
    1. Henson FMD, Bowe EA, Davies ME. Promotion of the intrinsic damage-repair response in articular cartilage by fibroblastic growth factor-2. Osteoarthritis Cartilage 2005;13:537-44.
    1. Chuma H, Mizuta H, Kudo S, et al. One day exposure to FGF-2 was sufficient for the regenerative repair of full-thickness defects of articular cartilage in rabbits. Osteoarthritis Cartilage 2004;12:834-42.
    1. Ishii I, Mizuta H, Sei A, et al. Healing of full-thickness defects of the articular cartilage in rabbits using fibroblast growth factor-2 and a fibrin sealant. J Bone Joint Surg Br 2007;89:693-700.
    1. Mariani E, Pulsatelli L, Facchini A. Signaling pathways in cartilage repair. Int J Mol Sci 2014;15:8667-98.
    1. Risbud MV, Shapiro IM. Role of cytokines in intervertebral disc degeneration: pain and disc content. Nat Rev Rheumatol 2014;10:44-56.
    1. Merz D, Liu R, Johnson K, Terkeltaub R. IL-8/CXCL8 and growth-related oncogene alpha/CXCL1 induce chondrocyte hypertrophic differentiation. J Immunol 2003;171:4406-15.
    1. Zelzer E, Olsen BR. Multiple roles of vascular endothelial growth factor (VEGF) in skeletal development, growth, and repair. Curr Top Dev Biol 2005;65:169-87.
    1. Xiao J, Chen X, Xu L, et al. PDGF regulates chondrocyte proliferation through activation of the GIT1- and PLCgamma1-mediated ERK1/2 signaling pathway. Mol Med Rep 2014;10:2409-14.
    1. Starkman BG, Cravero JD, Delcarlo M, Loeser RF. IGF-I stimulation of proteoglycan synthesis by chondrocytes requires activation of the PI 3-kinase pathway but not ERK MAPK. Biochem J 2005;389:723-9.
    1. Guntur AR, Rosen CJ. IGF-1 regulation of key signaling pathways in bone. BoneKEy Rep 2013;2:437.
    1. Su N, Jin M, Chen L. Role of FGF/FGFR signaling in skeletal development and homeostasis: learning from mouse models. Bone Res 2014;2:14003.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit