A systematic review of the concept and clinical applications of bone marrow aspirate concentrate in tendon pathology

Mohamed A Imam, James Holton, Saman Horriat, Ahmed S Negida, Florian Grubhofer, Rohit Gupta, Ali Narvani, Martyn Snow, Mohamed A Imam, James Holton, Saman Horriat, Ahmed S Negida, Florian Grubhofer, Rohit Gupta, Ali Narvani, Martyn Snow

Abstract

Tendon pathologies are a group of musculoskeletal conditions frequently seen in clinical practice. They can be broadly classified into traumatic, degenerative and overuse-related tendinopathies. Rotator cuff tears, Achilles tendinopathy and tennis elbow are common examples of these conditions. Conventional treatments have shown inconsistent outcomes and might fail to provide satisfactory clinical improvement. With the growing trend towards the use of mesenchymal stem cells (MSCs) in other branches of medicine, there is an increasing interest in treating tendon pathologies using the bone marrow MSC. In this article, we provide a systematic literature review documenting the current status of the use of bone marrow aspirate concentrate (BMAC) for the treatment of tendon pathologies. We also asked the question on the safety of BMAC and whether there are potential complications associated with BMAC therapy. Our hypothesis is that the use of BMAC provides safe clinical benefit when used for the treatment of tendinopathy or as a biological augmentation of tendon repair. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist while preparing this systematic review. A literature search was carried out including the online databases of PubMed, EMBASE, ClinicalTrial.gov and the Cochrane Library from 1960 to the end of May 2015. Relevant studies were selected and critically appraised. Data from eligible studies were extracted and classified per type of tendon pathology. We included 37 articles discussing the application and use of BMAC for the treatment of tendon pathologies. The Critical Appraisal Skills Program (CASP) appraisal confirmed a satisfactory standard of 37 studies. Studies were sub-categorised into: techniques of extraction, processing and microscopic examination of BMAC (n = 18), where five studies looked at the evaluation of aspiration techniques (n = 5), augmentation of rotator cuff tears (n = 5), augmentation of tendo-achilles tendon (n = 1), treatment of gluteal tendon injuries (n = 1), management of elbow epicondylitis (n = 2), management of patellar tendinopathy (n = 1) and complications related to BMAC (n = 5). Multiple experimental studies investigated the use of BMAC for tendon repair; nonetheless, there are only limited clinical studies available in this field. Unfortunately, due to the scarcity of studies, which were mainly case series, the current level of evidence is weak. We strongly recommend further future randomised controlled studies in this field to allow scientists and clinicians make evidence-based conclusions.

© The Authors, published by EDP Sciences, 2017.

Figures

Figure 1.
Figure 1.
Flow diagram of the search results.
Figure 1.
Figure 1.
Flow diagram of the search results.

References

    1. Zhang J, Wang JH (2010) Mechanobiological response of tendon stem cells: implications of tendon homeostasis and pathogenesis of tendinopathy. J Orthop Res 28(5), 639–643.
    1. Kannus P, Jozsa L (1991) Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients. J Bone Joint Surg Am 73(10), 1507–1525.
    1. Bi Y, Ehirchiou D, Kilts TM, Inkson CA, Embree MC, Sonoyama W, Li L, Leet AI, Seo BM, Zhang L, Shi S, Young MF (2007) Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nat Med 13(10), 1219–1227.
    1. Bruder SP, Jaiswal N, Haynesworth SE (1997) Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation. J Cellular Biochem 64(2), 278–294.
    1. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411), 143–147.
    1. Holton J, Imam M, Ward J, Snow M (2016) The basic science of bone marrow aspirate concentrate in chondral injuries. Orthop Rev (Pavia) 8(3), 6659.
    1. Imam MA, Mahmoud SSS, Holton J, Abouelmaati D, Elsherbini Y, Snow M (2017) A systematic review of the concept and clinical applications of bone marrow aspirate concentrate in orthopaedics. SICOT-J 3, 17.
    1. Broese M, Toma I, Haasper C, Simon A, Petri M, Budde S, Wehmeier M, Krettek C, Jagodzinski M(2011) Seeding a human tendon matrix with bone marrow aspirates compared to previously isolated hBMSCs – an in vitro study. Technol Health Care 19(6), 469–479.
    1. Okamoto N, Kushida T, Oe K, Umeda M, Ikehara S, Iida H (2010) Treating Achilles tendon rupture in rats with bone-marrow-cell transplantation therapy. J Bone Joint Surg Am 92(17), 2776–2784.
    1. Nadelson S, Nadelson LS (2014) Evidence-based practice article reviews using CASP tools: a method for teaching EBP. Worldviews Evid Based Nurs 11(5), 344–346.
    1. Bain BJ (1996) The bone marrow aspirate of healthy subjects. Br J Haematol 94(1), 206–209.
    1. Yamamura R, Yamane T, Hino M, Ohta K, Shibata H, Tsuda I, Tatsumi N (2002) Possible automatic cell classification of bone marrow aspirate using the CELL-DYN 4000 automatic blood cell analyzer. J Clin Lab Anal 16(2), 86–90.
    1. Kim M, Kim J, Lim J, Kim Y, Han K, Kang CS (2004) Use of an automated hematology analyzer and flow cytometry to assess bone marrow cellularity and differential cell count. Ann Clin Lab Sci 34(3), 307–313.
    1. Hyer CF, Berlet GC, Bussewitz BW, Hankins T, Ziegler HL, Philbin TM (2013) Quantitative assessment of the yield of osteoblastic connective tissue progenitors in bone marrow aspirate from the iliac crest, tibia, and calcaneus. J Bone Joint Surg Am 95(14), 1312–1316.
    1. Pierini M, Di Bella C, Dozza B, Frisoni T, Martella E, Bellotti C, Remondini D, Lucarelli E, Giannini S, Donati D (2013) The posterior iliac crest outperforms the anterior iliac crest when obtaining mesenchymal stem cells from bone marrow. J Bone Joint Surg Am 95(12), 1101–1107.
    1. Muschler GF, Boehm C, Easley K (1997) Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume. J Bone Joint Surg Am 79(11), 1699–1709.
    1. Hernigou J, Picard L, Alves A, Silvera J, Homma Y, Hernigou P (2014) Understanding bone safety zones during bone marrow aspiration from the iliac crest: the sector rule. Int Orthop 38(11), 2377–2384.
    1. Hernigou P, Homma Y, Flouzat Lachaniette CH, Poignard A, Allain J, Chevallier N, Rouard H (2013) Benefits of small volume and small syringe for bone marrow aspirations of mesenchymal stem cells. Int Orthop 37(11), 2279–2287.
    1. Hernigou P, Poignard A, Beaujean F, Rouard H (2005) Percutaneous autologous bone-marrow grafting for nonunions Influence of the number and concentration of progenitor cells. J Bone Joint Surg Am 87(7), 1430–1437.
    1. Hernigou P, Mathieu G, Poignard A, Manicom O, Beaujean F, Rouard H (2006) Percutaneous autologous bone-marrow grafting for nonunions. Surgical technique. J Bone Joint Surg Am 88(Suppl 1 Pt 2), 322–327.
    1. Kasten P, Beyen I, Egermann M, Suda AJ, Moghaddam AA, Zimmermann G, Luginbuhl R (2008) Instant stem cell therapy: characterization and concentration of human mesenchymal stem cells in vitro. Euro Cell Mater 16, 47–55.
    1. Fortier LA, Potter HG, Rickey EJ, Schnabel LV, Foo LF, Chong LR, Stokol T, Cheetham J, Nixon AJ (2010) Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model. J Bone Joint Surg Am 92(10), 1927–1937.
    1. Lee DH, Ryu KJ, Kim JW, Kang KC, Choi YR (2014) Bone marrow aspirate concentrate and platelet-rich plasma enhanced bone healing in distraction osteogenesis of the tibia. Clin Orthop Relat Res 472(12), 3789–3797.
    1. Jager M, Jelinek EM, Wess KM, Scharfstadt A, Jacobson M, Kevy SV, Krauspe R (2009) Bone marrow concentrate: a novel strategy for bone defect treatment. Curr Stem Cell Res Therapy 4(1), 34–43.
    1. Muschler GF, Nitto H, Matsukura Y, Boehm C, Valdevit A, Kambic H, Davros W, Powell K, Easley K (2003) Spine fusion using cell matrix composites enriched in bone marrow-derived cells. Clin Orthop Relat Res 407, 102–118.
    1. McCarrel T, Fortier L (2009) 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 27(8), 1033–1042.
    1. Chopp M, Li Y, Zhang ZG (2009) Mechanisms underlying improved recovery of neurological function after stroke in the rodent after treatment with neurorestorative cell-based therapies. Stroke 40(3 Suppl), S143–S145.
    1. Schwarz SC, Schwarz J (2010) Translation of stem cell therapy for neurological diseases. Transl Res 156(3), 155–160.
    1. Baksh D, Song L, Tuan RS (2004) Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med 8(3), 301–316.
    1. Gulotta LV, Kovacevic D, Ehteshami JR, Dagher E, Packer JD, Rodeo SA (2009) Application of bone marrow-derived mesenchymal stem cells in a rotator cuff repair model. Am J Sports Med 37(11), 2126–2133.
    1. Nejadnik H, Hui JH, Feng Choong EP, Tai BC, Lee EH (2010) Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med 38(6), 1110–1116.
    1. Brazelton TR, Rossi FM, Keshet GI, Blau HM (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290(5497), 1775–1779.
    1. Kopen GC, Prockop DJ, Phinney DG (1999) Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci USA 96(19), 10711–10716.
    1. Hayashi M, Zhao C, An KN, Amadio PC. 2011. The effects of growth and differentiation factor 5 on bone marrow stromal cell transplants in an in vitro tendon healing model. J Hand Surg Eur Vol 36(4), 271–279.
    1. Morizaki Y, Zhao C, An KN, Amadio PC (2010) The effects of platelet-rich plasma on bone marrow stromal cell transplants for tendon healing in vitro. J Hand Surg 35(11), 1833–1841.
    1. Zhao C, Chieh HF, Bakri K, Ikeda J, Sun YL, Moran SL, An KN, Amadio PC (2009) The effects of bone marrow stromal cell transplants on tendon healing in vitro. Med Eng Phys 31(10), 1271–1275.
    1. Renzi S, Ricco S, Dotti S, Sesso L, Grolli S, Cornali M, Carlin S, Patruno M, Cinotti S, Ferrari M (2013) Autologous bone marrow mesenchymal stromal cells for regeneration of injured equine ligaments and tendons: a clinical report. Res Vet Sci 95(1), 272–277.
    1. Torricelli P, Fini M, Filardo G, Tschon M, Pischedda M, Pacorini A, Kon E, Giardino R (2011) Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses. Int Orthop 35(10), 1569–1576.
    1. Neyton L, Godeneche A, Nove-Josserand L, Carrillon Y, Clechet J, Hardy MB (2013) Arthroscopic suture-bridge repair for small to medium size supraspinatus tear: healing rate and retear pattern. Arthroscopy 29(1), 10–17.
    1. Imam MA, Abdelkafy A (2016) Outcomes following arthroscopic transosseous equivalent suture bridge double row rotator cuff repair: a prospective study and short-term results. SICOT-J 2, 7.
    1. Ellera Gomes JL, da Silva RC, Silla LM, Abreu MR, Pellanda R (2012) Conventional rotator cuff repair complemented by the aid of mononuclear autologous stem cells. Knee Surg Sports Traumatol Arthrosc 20(2), 373–377.
    1. Hernigou P, Flouzat Lachaniette CH, Delambre J, Zilber S, Duffiet P, Chevallier N, Rouard H (2014) Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study. Int Orthop 38(9), 1811–1818.
    1. Havlas V, Kotaska J, Konicek P, Trc T, Konradova S, Koci Z, Sykova E (2015) Use of cultured human autologous bone marrow stem cells in repair of a rotator cuff tear: preliminary results of a safety study. Acta Chir Orthop Traumatol Cech 82(3), 229–234.
    1. Centeno CJ, Al-Sayegh H, Bashir J, Goodyear S, Freeman MD (2015) A prospective multi-site registry study of a specific protocol of autologous bone marrow concentrate for the treatment of shoulder rotator cuff tears and osteoarthritis. J Pain Res 8, 269–276.
    1. Stein BE, Stroh DA, Schon LC (2015) Outcomes of acute Achilles tendon rupture repair with bone marrow aspirate concentrate augmentation. Int Orthop 39(5), 901–905.
    1. Campbell KJ, Boykin RE, Wijdicks CA, Erik Giphart J, LaPrade RF, Philippon MJ (2013) Treatment of a hip capsular injury in a professional soccer player with platelet-rich plasma and bone marrow aspirate concentrate therapy. Knee Surg Sports Traumatol Arthrosc 21(7), 1684–1688.
    1. Gott M, Ast M, Lane LB, Schwartz JA, Catanzano A, Razzano P, Grande DA (2011) Tendon phenotype should dictate tissue engineering modality in tendon repair: a review. Discov Med 12(62), 75–84.
    1. Moon YL, Jo SH, Song CH, Park G, Lee HJ, Jang SJ (2008) Autologous bone marrow plasma injection after arthroscopic debridement for elbow tendinosis. Ann Acad Med Singapore 37(7), 559–563.
    1. Singh A, Gangwar DS, Singh S (2014) Bone marrow injection: a novel treatment for tennis elbow. J Nat Sci Biol Med 5(2), 389–391.
    1. Pascual-Garrido C, Rolon A, Makino A (2012) Treatment of chronic patellar tendinopathy with autologous bone marrow stem cells: a 5-year-followup. Stem Cells Int 2012, 953510.
    1. Bain BJ (2005) Bone marrow biopsy morbidity: review of 2003. J Clin Pathol 58(4), 406–408.
    1. Burkle CM, Harrison BA, Koenig LF, Decker PA, Warner DO, Gastineau DA (2004) Morbidity and mortality of deep sedation in outpatient bone marrow biopsy. Am J Hematol 77(3), 250–256.
    1. Bain BJ (2004) Bone marrow biopsy morbidity and mortality: 2002 data. Clin Lab Haematol 26(5), 315–318.
    1. Bain BJ. 2003. Bone marrow biopsy morbidity and mortality. Br J Haematol 121(6), 949–951.
    1. Husebye EE, Lyberg T, Roise O (2006) Bone marrow fat in the circulation: clinical entities and pathophysiological mechanisms. Injury 37(Suppl 4), S8–S18.
    1. Orlowski JP, Julius CJ, Petras RE, Porembka DT, Gallagher JM (1989) The safety of intraosseous infusions: risks of fat and bone marrow emboli to the lungs. Ann Emerg Med 18(10), 1062–1067.
    1. Hernigou P, Homma Y, Flouzat-Lachaniette CH, Poignard A, Chevallier N, Rouard H (2013) Cancer risk is not increased in patients treated for orthopaedic diseases with autologous bone marrow cell concentrate. J Bone Joint Surg Am 95(24), 2215–2221.

Source: PubMed

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