Autologous Bone Marrow Concentrate: Review and Application of a Novel Intra-Articular Orthobiologic for Cartilage Disease

Abstract

Younger adults, aged < 65 years, increasingly present to their physicians with advanced cartilage disease or post-traumatic osteoarthritis. A number of treatments exist for lessening patient pain and improving patient function. However, many patients are becoming aware of the potential of regenerative therapies and are now seeking solutions to the impaired biology underlying their conditions rather than addressing only their symptoms. Patients do not want to merely lessen their symptoms temporarily with a surgical procedure that replaces damaged tissue, but instead seek correction and repair of the underlying biology to regenerate damaged tissue and alleviate their symptoms altogether. Current therapies for patients with cartilage disease or osteoarthritis range from non-surgical intra-articular injections with biologics, such as hyaluronic acid (HA), to total joint arthroplasty for advanced stages of disease. Total joint arthroplasty is a successful procedure for patients aged > 65 years; however, the limited long-term durability of implanted prostheses decreases the preference of using such methods in more active patients aged < 65 years. The potential of cell-based orthobiologic injection therapies (pertaining to therapeutic injectables that aim to restore the biologic environment and/or structural components of diseased or damaged musculoskeletal tissue) is of tremendous interest for younger, more active patients, and is even more appealing in that such therapy can be delivered at point-of-care in the clinic during an office visit. Notably, the exponential rate of progress in biotechnology has allowed for immediate application of myriad novel therapies prior to clear evidence of benefit from randomized clinical trials. Orthobiologic intra-articular injection therapies include HA and platelet-rich plasma (PRP). We report on current, available findings for a third-generation intra-articular orthobiologic injectable therapy for cartilage disease, bone marrow concentrate (BMC). Bone marrow concentrate contains mesenchymal stem cells (MSCs), hematopoetic stem cells, platelets (containing growth factors), and cytokines. The anti-inflammatory and immunomodulatory properties of bone marrow stem cells (BMSCs) can facilitate regeneration of tissue. Additionally, BMSCs enhance the quality of cartilage repair by increasing aggrecan content and tissue firmness. Following bone marrow aspiration (BMA), BMC is easily prepared using centrifugation, and is available for a same-day procedure with minimal manipulation of cells, thus complying with US Food and Drug Association (FDA) restrictions. To date, there are no published randomized controlled trials on the efficacy of use of autologous BMC intra-articular injections performed as a same-day in-office procedure for treating patients with cartilage disease; however, several publications have reported the ease of use of this method, its strong safety profile, and the fundamental science suggesting great therapeutic potential.

Clinical Aspects of Regenerative Medicine

“…The use of first-generation biologic injectables, like HA, have been successful in the treatment of patients with painful OA of the knee [1]. PRP represented the second-generation of biologic injectables for multiple musculoskeletal disorders, and was the first of autologous nature.…”

“…In an effort to correct the disordered biology, orthobiologics have emerged both as injectable therapeutic options at the bedside and as adjuncts to surgical strategies. Orthobiologics pertain to therapeutic injectables which aim to restore the biologic environment and/or structural components of diseased or damaged musculoskeletal tissue [1]. Cell-based orthobiologic injection therapies today include platelet-rich plasma (PRP) and bone marrow concentrate (BMC).…”

Emerging Potential of Cell Based Therapies for Articular Cartilage Repair and Regeneration

“…BMC thus possess anti-inflammatory, angiogenic and immunomodulatory properties that can potentially enhance cartilage repair. 83 Basic science and animal model studies have reported promising results for using BMC in treating cartilage pathology. 84,85 These preclinical trials have led to a few small clinical studies.…”

“…This paracrine activity of MSCs is thought to be one of the major means by which these cells mediate anti-inflammatory, anti-apoptotic, antifibrotic, angiogenic, mitogenic, and wound-healing properties that have proliferative effects on cells. 42,44,62,83 The study by Cassano et al 119 reviewed the growth factor and cytokine levels between PRP and BMC. They found that BMC had 172.5x the concentration of vascular endothelial growth factor (VEGF), 78x the concentration of interleukin-8 (IL-8), 4.6x the concentration of interleukin-1beta (IL-1 β), 3.4x the concentration of transforming growth factor-β 2 (TGF-β 2 ) and 1.3x the concentration of platelet derived growth factor (PDGF).…”

Mesenchymal stem cell response to growth factor treatment and low oxygen tension in 3-dimensional construct environment

“…A wide spectrum of treatments are available, from non-pharmacological modalities to dietary supplements and pharmacological therapies, as well as minimally invasive procedures involving injections of various substances aimed at restoring joint homeostasis and providing clinical improvement and possible disease modifying effects [34][35][36][37][38][39][40][41][42][43][44][45] . These injections are sometimes painful and are oftentimes combined with local anesthetics to alleviate the discomfort of the injection.…”