Bone marrow aspirate concentrate (BMAC) as a clinical effective solution for joint tissue treatment
Bone marrow can be entitled as a crucible of various cellular components, containing hematopoetic stem cells (HSCs), mesenchymal stem cells (MSCs) and platelets (PLTs). First mentioned cells are able to differentiate into blood cells family, while MSCs have the ability to differentiate into various of mesenchymal cells tissue, such as bone, cartilage, fat and muscles1. Taking into account this capability of the MSCs, the researchers begin to consider the bone marrow aspirate (BMA) as a therapeutic agent with promising potential for joint tissue regeneration2. Nevertheless, the native BMA contains a significant amount of HSCs and fat tissue, while MSCs appears as 0.001% of all nucleated cells, thus attempt to concentrate cells seems to be a vital approach3. The acquiring procedure of concentrated bone marrow aspirate (BMAC) allows to increase not only the MSCs but also PLTs, which are a significant source of growth factors an inductors of many regeneration processes4,5.
MSCs are characterized with the reparative and trophic properties, which allows them to migrate towards the damaged tissue. Additionally, at the moment of activation, the MSCs can act as a immunosuppressive factor, balancing or inhibiting the immunologic cells6, but also together with PLTs they took part in production of factors responsible for reduction of cell apoptosis, fibrosis, and inflammation process7,8. The growth factors which are secreted by both cells are among many others including platelet derived growth factors (PDGF), transforming growth factor β1 (TGF- β1), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 2 (FGF-2), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF)1,9.
It is well established that intra-articular injection of MSCs and PLTs in a form of BMAC product has shown that regeneration processes of the joint structures can occur10. Horie et al. described that MSCs implementation into the joint will increase the expression of collagen type II11. Growth factors secreted by the PLTs can positively affect the production and secretion of tissue extracellular matrix (ECM) components like ACAN, COL2A1, and HA. As this leads to induced biosynthesis of ECM components like aggrecan, type II collagen and hyaluronic acid, which will contribute significantly to increase of regeneration processes of articular cartilage12.
All of the mentioned effects makes the BMAC injections a highly recommendable therapy for a joint associated pathologies or injuries. Kim et al. (2014) described that BMAC injection significantly improved both knee pain and functions in the patients with degenerative arthritis of knee up to 12 months13. Additionally, in the study of Buda et al. (2013), the assessment of BMAC with collagen membrane was well tolerated in case of chondral lesions treatment. After three years of the study, the patients KOOS score improved by 52 points, the MRI showed an osteochondral regeneration of the lesion site and histology analysis pointed out that cartilaginous tissue contains predominantly type II collagen and proteoglycan-rich matrix14.
- Madry H, Gao L, Eichler H, Orth P, Cucchiarini M. Bone Marrow Aspirate Concentrate-Enhanced Marrow Stimulation of Chondral Defects. Stem Cells International. 2017;2017:1-13. doi:10.1155/2017/1609685
- Holton J, Imam M, Ward J, Snow M. The basic science of bone marrow aspirate concentrate in chondral injuries. Orthop Rev. 2016;8(3). doi:10.4081/or.2016.6659
- Orthopaedic Surgery Hospital, University of Heidelberg, Schlierbacher Landstr. 200a, D-69118 Heidelberg, Germany, Kasten P, Beyen I, et al. Instant stem cell therapy: Characterization and concentration of human mesenchymal stem cells in vitro. eCM. 2008;16:47-55. doi:10.22203/eCM.v016a06
- Holton J, Imam MA, Snow M. Bone Marrow Aspirate in the Treatment of Chondral Injuries. Front Surg. 2016;3. doi:10.3389/fsurg.2016.00033
- Farley A, Hendry C, McLafferty E. Blood components. Nurs Stand. 2012;27(13):35-42. doi:10.7748/ns2012.11.27.13.35.c9449
- Uccelli A, Pistoia V, Moretta L. Mesenchymal stem cells: a new strategy for immunosuppression? Trends in Immunology. 2007;28(5):219-226. doi:10.1016/j.it.2007.03.001
- 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(1):333-342. doi:10.1007/s00167-016-3981-9
- Andia I, Maffulli N. Platelet-rich plasma for managing pain and inflammation in osteoarthritis. Nat Rev Rheumatol. 2013;9(12):721-730. doi:10.1038/nrrheum.2013.141
- Andia I, Sanchez M, Maffulli N. Tendon healing and platelet-rich plasma therapies. Expert Opinion on Biological Therapy. 2010;10(10):1415-1426. doi:10.1517/14712598.2010.514603
- Fellows CR, Matta C, Zakany R, Khan IM, Mobasheri A. Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair. Front Genet. 2016;7. doi:10.3389/fgene.2016.00213
- Horie M, Choi H, Lee RH, et al. Intra-articular injection of human mesenchymal stem cells (MSCs) promote rat meniscal regeneration by being activated to express Indian hedgehog that enhances expression of type II collagen. Osteoarthritis and Cartilage. 2012;20(10):1197-1207. doi:10.1016/j.joca.2012.06.002
- Sundman EA, Cole BJ, Karas V, et al. The Anti-inflammatory and Matrix Restorative Mechanisms of Platelet-Rich Plasma in Osteoarthritis. Am J Sports Med. 2014;42(1):35-41. doi:10.1177/0363546513507766
- 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(8):1505-1511. doi:10.1007/s00590-013-1393-9
- Buda R, Vannini F, Cavallo M, et al. One-step arthroscopic technique for the treatment of osteochondral lesions of the knee with bone-marrow-derived cells: three years results. Musculoskelet Surg. 2013;97(2):145-151. doi:10.1007/s12306-013-0242-7