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Bone Marrow Aspirate Concentrate

Bone Marrow Aspirate Concentrate (BMAC) is a biologic product used clinically to promote tissue repair and regeneration. The preparation method involves obtaining a patient's bone marrow fluid and then concentrating cells from the bone marrow that can assist in repair, such as mesenchymal stem cells, platelets, white blood cells, and anti-inflammatory substances. The concentrated BMAC can be directly injected into the affected area for treatment. It is currently more commonly used for conditions related to joints, soft tissues, and bones, depending on the patient's condition, physician assessment, and treatment goals.

Introduction to Bone Marrow

Bone marrow is a soft, viscous tissue with a semi-solid consistency. It is primarily located within the spongy bone of bones, often found at the ends of the bone marrow cavities. In adults, bone marrow is mainly distributed in bones such as the pelvis, sternum, and ribs. The structure of spongy bone resembles a mesh-like network with numerous trabeculae interwoven to provide support and enhance structural strength. Undifferentiated precursor cells and mesenchymal stem cells (MSCs) are found within spongy bone. These cells, as they mature, move into the bone marrow cavity and are then transported throughout the body. When extracting bone marrow fluid, mesenchymal stem cells (MSCs) are obtained from spongy bone due to their potential to differentiate into muscles, bones, and cartilage, making them valuable for regenerative repair.

Introduction to Mesenchymal Stem Cells (MSCs)

Mesenchymal Stem Cells (MSCs) are multi-functional stem cells present in various tissues and organs of adults, including bone marrow, adipose tissue, muscles, skin, and more. MSCs possess differentiation potential, but their role is more like that of "commanders" compared to directly differentiating into specific tissues. They can release various growth factors, cell signals, and immunomodulatory molecules to regulate the activity of surrounding cells, awakening progenitor cells within tissues for differentiation and repair. This indirect influence can promote tissue repair, vascular neogenesis, cell proliferation, and other processes.

MSCs within the human body exhibit immunomodulatory properties, suppress cell apoptosis (programmed cell death), and regulate differentiation.

MSCs have immunomodulatory capabilities, meaning they can assist in regulating the activity of the immune system, helping to balance immune responses. MSCs can release various immunomodulatory molecules, such as cytokines and chemokines, which can influence the activity of immune cells, modulate the intensity of immune responses, and reduce excessive inflammation. This makes MSCs potentially valuable in the treatment of autoimmune diseases and anti-rejection responses.

Suppression of Cell Apoptosis:
Cell apoptosis is a programmed cell death process, and MSCs have the ability to inhibit this death process. They can release anti-apoptotic proteins and growth factors, protecting damaged cells from apoptosis, helping maintain cell survival within tissues, and promoting tissue repair.

Regulation of Differentiation:
MSCs can release growth factors and signaling molecules that influence the differentiation direction of surrounding cells. They guide progenitor cells to become the desired cell types, promoting tissue repair and regeneration.

In addition, MSCs contain various growth factors, including Transforming Growth Factor-beta (TGF-β), Platelet-Derived Growth Factor (PDGF), and Bone Morphogenetic Proteins (BMPs).

Transforming Growth Factor-beta (TGF-β):
TGF-β is a critical growth factor that regulates cell proliferation, differentiation, and extracellular matrix production. It plays a crucial role in tissue repair by promoting the regeneration of cartilage and bone tissue and participating in wound healing processes.

Platelet-Derived Growth Factor (PDGF):
PDGF is a factor that stimulates the growth and differentiation of platelets, fibroblasts, and endothelial cells. It can promote vascular neogenesis and tissue repair, aiding in wound healing and regeneration processes.

Bone Morphogenetic Proteins (BMPs) BMP-2 and BMP-7:
BMPs are a class of growth factors that play a crucial role in the formation and regeneration of bone tissue. BMP-2 and BMP-7 can promote the proliferation and differentiation of bone cells and are involved in bone repair and regeneration.

The presence of these growth factors plays a crucial role in the process of tissue repair and regeneration by mesenchymal stem cells. Mesenchymal stem cells can release these growth factors, stimulating the proliferation, differentiation, and regeneration of surrounding tissues, promoting wound healing, and simultaneously exerting anti-inflammatory effects to reduce inflammation. In the context of joint repair, the capabilities of mesenchymal stem cells are particularly significant in the treatment of joint degeneration and injuries[2].

Anti-inflammatory Proteins in Bone Marrow Aspirate Concentrate (BMAC)

In clinical applications and research, the therapeutic mechanism of bone marrow aspirate concentrate extends beyond mesenchymal stem cells and also involves various growth factors and cytokines present in bone marrow. These biomolecules play crucial roles in tissue repair and regeneration by stimulating cell proliferation, differentiation, and repair processes, while also regulating immune responses and inflammation to facilitate wound healing. One such molecule is Interleukin-1 receptor antagonist (IL-1Ra), which acts as an antagonist to Interleukin-1 (IL-1). IL-1 is a cytokine that promotes inflammation and immune responses, participating in various physiological and pathological processes, including inflammation, immune regulation, and tissue repair. IL-1Ra functions by competing with IL-1 for receptors, inhibiting the mechanisms that lead to inflammation. Compared to blood, bone marrow concentrate contains a significant amount of IL-1Ra. This suggests that bone marrow concentrate may be more effective in pain relief and anti-inflammatory effects compared to other blood products like platelet-rich plasma (PRP)[3].

Key Functions of BMAC

  • Cartilage Repair and Regeneration Response: PDGF, TGF-β

  • Regulation or Attenuation of Inflammatory Responses: IL-1Ra, TGF-β

  • Angiogenesis Response: PDGF

Clinical Application

Hip Joint Avascular Necrosis [1]

Intervertebral Disc Annular Tear [3]

Grade 3 & 4 Degenerative Joint Disease [2]

Incomplete Bone Healing [4]

Cartilage Repair [5]

Reference List

  • [1] Kruel, A. V. S., Ribeiro, L. L., Gusmão, P. D., Huber, S. C., & Lana, J. F. S. D. Orthobiologics in the treatment of hip disorders. World journal of stem cells, 2021; 13(4), 304.

  • [2] Themistocleous, G. S., Chloros, G. D., Kyrantzoulis, I. M., Georgokostas, I. A., Themistocleous, M. S., Papagelopoulos, P. J., & Savvidou, O. D.. Effectiveness of a single intra-articular bone marrow aspirate concentrate (BMAC) injection in patients with grade 3 and 4 knee osteoarthritis. Heliyon, 2018; 4(10).

  • [3] Hernigou, P., Dubory, A., Homma, Y., Guissou, I., Flouzat Lachaniette, C. H., Chevallier, N., & Rouard, H. Cell therapy versus simultaneous contralateral decompression in symptomatic corticosteroid osteonecrosis: a thirty year follow-up prospective randomized study of one hundred and twenty five adult patients. International orthopaedics, 2018; 42, 1639-1649.

  • [4] Modest, J. M., Lemme, N. J., Testa, E. J., Evans, A. R., & Reid, D. B. Successful Fracture Healing for Femoral Neck Nonunion with Bone Marrow Aspirate Concentrate. Rhode Island Medical Journal, 2022; 105(2), 13-16.

  • [5] Gobbi, A., Karnatzikos, G., Scotti, C., Mahajan, V., Mazzucco, L., & Grigolo, B. (2011). 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, 2(3), 286-299.

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