Bone Marrow Aspirate Concentrate and Expanded Stem Cell Applications in Orthopaedics

Mesenchymal Stem Cells (MSCs) have multipotent plasticity. They demonstrate the ability to differentiate into various cell types. These include bone, tendon, cartilage, muscles and nerve [1-6]. Subsequently, they can have a role in the coming era of medicine as they have the potential to contribute to the regeneration and reconstruction of different tissues, especially in musculoskeletal medicine. As yet, Bone marrow is regarded as the most attractive source of MSCs [7, 8] and for the last few years, numerous interventionists have employed unprocessed Bone Marrow Aspirate (BMA), to incite healing.

Bone Marrow (BM) is a major hematopoietic organ in the human body being the main primary lymphoid organ; it is the source of production of all blood lineages. These cells are produced through an interaction between BM hematopoietic cells and the surrounding microenvironment in a unit called the stem cell niche that involves several cytokines, growth factors and transcriptional factors. The following chapter will entail an overview of MSCs, their isolation and clinical application.

Stem cell research is rapidly progressing especially in the field of orthopaedic surgery. The processes of stem cell extraction, expansion, injection, evaluation in preclinical studies and translation into human trials are challenging. Due to the novelty and complexity of stem cell techniques, several methodological and ethical issues need to be explored. Assessment of risk versus benefit proportionality, selecting appropriate participants and determining a reliable therapeutic end point are major challenges for stem cell trials in humans. In this chapter, we are discussing ethical and methodological challenges in the clinical use and research of stem cells and Bone Marrow Aspirate Cells.

Stem cells research is considered as one of the most promising technics recently. In orthopedic, the use of stem cells therapy on humans is still challenging. As a result of the novelty of these technics, the researchers need a guideline to highlight the key issues in the clinical practice of stem cells research to protect the wellbeing, safety and rights of the research subjects. Moreover, several methodological and ethical issues are still questionable regarding stem cells trials in humans as: (1) avoiding expertise Bias; (2) selecting appropriate participants; and (3) determining a reliable therapeutic end point. So, in this chapter we will highlight the key points on how to run a clinical trial and how to overcome the methodological challenges in the research of stem cells regarding orthopedic surgery.

Non-unions occur mostly due to fracture stability, decrease in blood supply, or both. The cause of non-union is subcategorised into biological and mechanical factors. There are several risk factors for non-union which include -but are not limited to smoking, diabetes mellitus, infection, open or compound fractures, senility, inadequate nutrition and some drugs like NSAIDs. Mechanical factors include the application of electric fields, physical stimulation and ultrasound. The biological materials include osteoconductive agents such as tricalcium phosphate (TCP), hydroxyapatite (HA) preferably with added Osteoinductive agents, which enhance migration, proliferation and differentiation of cells to promote fracture healing. Such agents as Platelets rich plasma (PRP), Bone marrow aspirate concentrate (BMAC), and Bone morphogenetic protein (BMP).

Mesenchymal stem cells (MSCs) are perceived as an innovative approach to manage osteoarthritis (OA). There are anticipations that MSCs might improve symptoms, function, suppress inflammation and improve cartilage healing. Notwithstanding, the usage of MSCs in the treatment of osteoarthritis needs to be adequately represented, as there are many crucial determinants that should be considered before definitive reliable conclusions concerning the role of MSCs as a treatment option of OA can be drawn.

Mesenchymal Stem Cells (MSCs) are believed to have multipotent plasticity with the capability to differentiate along multiple cell lineages such as cartilage. This was the foundation on which BMAC has been popularised in the management of cartilage defects. There have been numerous animal models that have shown clear benefit of BMAC to augment healing and improve cartilage repair when compared with traditional cartilage healing techniques; such as micro-fracture. This has been translated into beneficial studies in humans; as diseases of the articular cartilage have such a huge socio-economic burden affecting patient health related quality of life. These pioneering studies have led to a huge increase in the popularity of BMAC as a biological augment. Its key cellular components and growth promoting factors aid tissue regeneration and repair with the potential to produce true hyaline articular. This has clear advantage over the frequently encountered and inferior fibrocartilage from traditional methods of repair, such as microfracture and mosaicoplasty.

Avascular necrosis (AVN) is characterized by cell death of trabecular bone leading to bone collapse and subsequent joint destruction. Recently, application of bone marrow derived MSCs has been proposed as adjunctive treatment to core decompression for osteonecrosis of femoral head. There have been several studies, which report that BMAC application results in the improvement of outcomes; nevertheless, it is dependent on the stage of osteonecrosis. Superior outcomes are reported, similar to bone preserving procedures in the pre collapse stages. Additionally, the technique has not been associated with any significant complications. The current results are encouraging, however, more studies are required.

Nerve injuries either peripheral or central are extremely frequent in clinical practice. The impairment of sensory and motor functions may have distressing effects on the social and professional activities of these patients, most of whom are young and may acquire life-long disabilities. The extent of disability and patient suffering after Spinal Cord Injuries (SCI), as well as the high cost of care, continues to motivate research into effective interventions. Nerve surgery is aimed at motor and sensory reinnervation, but often a deficit in the functionality remains. As cell therapy and tissue engineering have been receiving a great deal of attention in recent decades, and are widely used in different areas, Therefore, the utilization of bone marrow aspirate concentrate in peripheral nerve repair techniques as well as after spinal cord injury is tried in order to optimize the regeneration process. In this chapter, we will discuss the evidence in the literature regarding the clinical and experimental application of bone marrow aspirate concentrate as a major source of mesenchymal stem cells in treatment of peripheral nerve and spinal cord injuries.

The use of autogenous bone marrow aspirate concentrate (BMAC) may offer a nonsurgical treatment of lumbar degenerative disc disease. It can also be used to enhance the cervical spine fusion. This chapter focuses on: the feasibility for using BMAC in spine surgery, host factors that may affect the outcome, the local morbidity of aspiration, and outcome after application of BMAC.

Tendon pathologies represent a group of musculoskeletal conditions commonly viewed in orthopaedic and rheumatology clinics. They are classified into traumatic, degenerative and over-use related types. As yet, the majority of conventional approaches have unpredictable results and regularly fail to produce satisfying clinical recovery. With increasing indication of the successful utilisation of MSCs in different divisions of medicine, there is significant interest in employing expanded stem cells to manage these pathologies. Here, we investigate written reports concerning the employment of MSC for managing tendon pathologies.

In this chapter, we aim to describe the current literature published on the uses of BMAC in the management of foot and ankle disorders. Animal and human studies suggest promising results on the usage of BMAC in augmenting arthrodesis and bone healing. Little evidence is published demonstrating the potential benefits of BMAC used in conjunction with foot and ankle surgery.

The uses of expanded stem cells and BMAC have always been linked with potential concerns. The aim of this chapter is to highlight the potential concerns that have been reported in the available literature.