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Biologics

Bone Marrow Aspirate (BMA)
What is BMA?

BMA is derived from a patient's bone marrow. It contains a heterogeneous mix of white blood cells—including stem cells, progenitor cells, lymphocytes and granulocytes—and platelets.

stemcell-progenitorcell-differentiation-
Composition of 
Bone Marrow Aspirate

Stem Cells - Have the potential to convert to osteoblasts, chondrocytes and other terminal tissue types ¹ ² ³ ⁴ ⁵ ⁶

 

Stem cells differentiate into many different types of cells. There are several types of stem cells, including hematopoietic and mesenchymal. They vary in differentiation potential and the terminal cell types they can become.

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  • Hematopoietic stem cells (HSCs) differentiate into blood cell components.

  • Mesenchymal stem cells (MSCs) have the capability to differentiate into many different cell types responsible for repair or growth of bone, cartilage, muscle, tendons, ligaments and connective tissue.

Progenitor Cells - Convert to terminal tissue; support angiogenesis; release BMP-2 and BMP-6; activate dormant cells.

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Endothelial progenitor cells also retain the ability to differentiate into other cell types, but to a lesser extent than stem cells. Progenitor cells are capable of releasing bone morphogenetic protein 2 (BMP-2) and BMP-6, two bone morphogenetic proteins that play a role in bone formation. ⁷ ⁸ ⁹

Lymphocytes - Support the migration and proliferation of endothelial progenitor cells.

 

Lymphocytes are small white blood cells that play a large role in immune response by protecting the body from disease. Lymphocytes also support the growth of endothelial progenitor cells, which can stimulate angiogenesis, release BMP-2 and BMP-6 and up-regulate the production of BMP-2. ¹⁰

Granulocytes - Support angiogenesis through release of vascular endothelial growth factors (VEGF); mediate inflammation

 

Granulocytes are a type of white blood cell filled with granules that digest microorganisms. Granulocytes release growth factors that support the development of new blood vessels (angiogenesis) necessary to support tissue regeneration and bone formation. ¹¹ ¹²

Monocytes/Macrophages - Monocytes assist in pathogen recognition and eventually become macrophages, which engulf and destroy pathogens as well as playing a critical role in tissue regeneration and repair. ¹³

Platelets - Rich source of growth factors that support proliferation and differentiation

 

Platelets are rich in growth factors, which play a critical role in the process of stem cell differentiation. Growth factors instruct stem cells to differentiate through proteins, which bind to receptors on the surface of the cell. A signal is delivered to the nucleus to turn off or turn on certain genes, which generates the proteins that dictate cell differentiation. ¹⁴

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Commonly used applications

BMA can be refined during, or post-aspiration, using advanced technology to create a solution high in HSCs and MSCs that can support the regeneration of tissue, cartilage, muscle, marrow, tendons, ligaments ¹ ² ³ ¹⁸. This makes it a promising candidate for use in:

  • Orthopedics & Sport Medicine

  • Pain Rehabilitation & Pain Management

  • Cosmetic & Aesthetic Medicine 

  • Dentistry

  • Oral & Maxillofacial Surgery

  • Veterinarian

Not all Bone Grafts & BMA solutions are Equal

With the rise in popularity of BMA in regenerative medicine, many systems and methods of preparation have been proposed. However, it is important to understand that not all BMA preparations are created equal and therefore may not provide the optimal conditions for healing. 

 

When selecting a BMA system, it is important to consider the following items -

1. Minimally Invasive Bone Grafts

  • There has been a shift from traditional repair surgery to more sophisticated methods, including less invasive surgical techniques and the use of biologics.

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  • Extracting morselized bone from the Iliac crest is a highly invasive procedure performed in the operating room that can generate significant donor site morbidity. In contrast, harvesting intact cancellous bone cores without disrupting the highly organized living tissue is superior as these cores maintain their micro-vascular network within the graft, promoting bone callus formation/remodeling and do not exhibit extensive resorption. ¹⁶ ¹⁷

2. High Quality BMA

  • BMA is rich in HSCs and MSCs, however, it requires special refinement to isolate these regenerative cells from peripheral blood and waste byproducts. This high-quality BMA may be used as an injectate for stem cell therapy or be combined with bone graft material to create a total solution that can be performed quickly and easily to provide support to bone formation.

Product Information
Product Information
BMAC

On Harvest Terumo BCT SmartPrep platform, The BMAC system is used to concentrate the stem cells found in bone marrow aspirate draw from the iliac crest. For more than a decade, the BMAC system has delivered quality, flexibility and reliability—and the highest stem cell concentration and yield compared to four other systems.

Product Information
Marrow Cellutions

Marrow Cellution™ bone graft kits provide high quality bone marrow aspirate and cancellous bone autograft, collected from numerous sites within the marrow space – achieving the gold standard of autograft in a minimally invasive manner.

References

  1. Matsumoto T, Kawamoto A, Kuroda R, et al. Therapeutic potential of vasculogenesis and osteogenesis promoted by peripheral blood CD34-positive cells for functional bone healing. Am J Pathol. 2006;169(4):1440-1457.

  2. Matsumoto T, Mifune Y, Kawamoto A, et al. Fracture induced mobilization and incorporation of bone marrow-derived endothelial progenitor cells for bone healing. J Cell Physiol. 2008;215(1):234-242.

  3. Mifune Y, Matsumoto T, Kawamoto A, et al. Local delivery of granulocyte colony stimulating factor-mobilized CD34-positive progenitor cells using bioscaffold for modality of unhealing bone fracture. Stem Cells. 2008;26(6):1395-1405.

  4. McArdle A. Manipulation of stem cells and their microenvironment for tissue engineering. Surgery: Current Research. 2013;03(03).

  5. Caplan A. Mesenchymal stem cells: the past, the present, the future. Cartilage. 2010;1(1):6-9.

  6. Caplan A. What's in a name? Tissue Engineering Part A. 2010;16(8):2415-2417.

  7. Jung Y, Song J, Shiozawa Y, et al. Hematopoietic stem cells regulate mesenchymal stromal cell induction into osteoblasts thereby participating in the formation of the stem cell niche. Stem Cells. 2008;26(8):2042-2051.

  8. Kuroda R, Matsumoto T, Kawakami Y, Fukui T, Mifune Y, Kurosaka M. Clinical impact of circulating CD34-positive cells on bone regeneration and healing. Tissue Engineering Part B: Reviews. 2014;20(3):190-199.

  9. El Khassawna T, Serra A, Bucher C, et al. T Lymphocytes influence the mineralization process of bone. Front Immunol. 2017;8:562.

  10. Ono T, Okamoto K, Nakashima T, et al. IL-17-producing γδ T cells enhance bone regeneration. Nat Commun. 2016;7:10928.

  11. Kusumanto Y, Dam W, Hospers G, Meijer C, Mulder N. Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis. 2003;6(4):283-287.

  12. Seignez C, Phillipson M. The multitasking neutrophils and their involvement in angiogenesis. Curr Opin Hematol. 2017;24(1):3-8.

  13. Das A, Sinha M, Datta S, et al. Monocyte and macrophage plasticity in tissue repair and regeneration. Am J Pathol. 2015;185(10):2596-2606.

  14. Amable P, Carias R, Teixeira M, et al. Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors. Stem Cell Res Ther. 2013;4(3):67.

  15. Ríos D, López C, Carmona J. Platelet-rich gel supernatants stimulate the release of anti-inflammatory proteins on culture media of normal equine synovial membrane explants. Vet Med Int. 2015;2015:547052.

  16. Wang W, Yeung K. Bone grafts and biomaterials substitutes for bone defect repair. A review. Bioactive Materials. 2017;2(4):224-227.

  17. Bleuming SA, He XC, Kodach LL, Hardwick JC, Koopman FA, Ten Kate FJ, van Deventer SJ, Hommes DW, Peppelenbosch MP, Offerhaus GJ, Li L, van den Brink GR (Sep 2007). "Bone morphogenetic protein signaling suppresses tumorigenesis at gastric epithelial transition zones in mice". Cancer Research. 67 (17): 8149–55.

  18. Hernigou P, Poignard A, Manicom O, Mathieu G, Rouard H. The use of percutaneous autologous bone marrow transplantation in nonunion and avascular necrosis of bone. J Bone Joint Surg Br. 2005;87(7):896-902.

  19.  Tondreau T, Meuleman N, Delforge A, et al. Mesenchymal stem cells derived from CD133-positive progenitor cells using bioscaffold for modality of unhealing bone fracture. Stem Cells. 2008;26(6):1395-1405.

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