Exploring The Contribution Of The Skeletal Stem Cell To Spinal Fusion: From Clinical Practice to Pathophysiology.

Abstract

As global demographics shift towards an ever increasingly aged population, the prevalence of age-related orthopaedic and spinal conditions has increased substantially. Conditions, such as osteoporosis and frailty, have an increased incidence within the ageing population. These conditions not only elevate the risk of fracture and deformity but also increase the complication rates during surgical interventions which involve bony fusion. Spinal fusion, aimed at stabilizing the spine by joining two or more vertebrae, is a well-established technique, but its success is heavily influenced by the patient�s bone quality and overall health status. With the rising demand for spinal surgeries among older patients, there is a critical need for innovations that improve the outcomes of these procedures. This thesis, �Exploring The Contribution Of The Skeletal Stem Cell To Spinal Fusion: From Clinical Practice to Pathophysiology,� addresses these challenges by exploring both clinical advancements and biological techniques that can enhance spinal fusion outcomes, particularly in vulnerable populations. One of the key areas of investigation is the potential role of human skeletal stem cells (hSSCs) in improving bone healing and promoting successful fusion, offering a promising alternative to traditional bone grafts and mesenchymal stromal cells (MSCs). The research spans from clinical practice to laboratory investigations, providing a holistic view of the current landscape of spinal fusion, with particular emphasis to spinal surgery in Ireland. It also introduces novel diagnostic tools to assess bone health and explores the latest technological advancements in surgical techniques, such as robotic-assisted surgery and image-guided navigation. By investigating both the biological and technological aspects of spinal fusion, this thesis aims to bridge gaps between clinical needs and emerging therapies, with a particular focus on the therapeutic potential of hSSCs in regenerative medicine. The thesis begins with a detailed review of the anatomy of the spine and tissues involved in spinal fusion, including bone, intervertebral discs, ligaments, and the spinal cord. It explains the processes of bone formation, remodelling, and repair mechanisms, focusing on skeletal stem cells� potential applications in tissue engineering and regenerative medicine. Following this, a historical review of spinal fusion is provided, from early treatments to modern-day advancements. It covers the evolution of techniques such as pedicle screw fixation and robotic-assisted surgeries. The chapter also discusses the complications associated with spinal fusion, including pseudarthrosis and the importance of precision in surgical techniques. Chapter 4 reviews modern technologies, such as image-guided navigation and robotic-assisted surgery, highlighting their role in improving precision and outcomes in spinal fusion surgeries. It also explores cost-effectiveness and future developments, including augmented reality in surgical navigation. Chapters 5 and 6 address the increased risks in performing spinal fusion on osteoporotic and frail patients, exploring the epidemiology, diagnosis, and interventions for osteoporosis, sarcopenia, and frailty. Emphasis is placed on optimizing surgical preparation for these vulnerable groups. Chapters 7 and 8 investigate the current evidence on potential alternatives to iliac crest bone autograft. Chapter 7 compares iliac crest bone grafts to cell-based grafts, while Chapter 8 compares recombinant human bone morphogenetic proteins (rhBMP) to traditional bone grafts. These sections analyse the outcomes of these techniques in spinal fusion and evaluate their effectiveness in promoting bone healing and fusion. Chapter 9 includes a meta-analysis on the diagnostic accuracy of Hounsfield units (HU) in computed tomography compared to dual-energy X-ray absorptiometry (DEXA) for diagnosing osteoporosis in spinal surgery patients, emphasizing the clinical utility of Hounsfield units for preoperative assessment and identifying these higher risk patients. Chapter 10 further investigates the use of the HU as a means of predicting those patients at risk of mal- or non-union for specific cases of anterior cervical discectomy and fusion. The optimal method of harvesting cells for fusion procedures remains elusive. In Chapter 12 we propose a new technique, navigation-assisted vertebral body bone marrow aspiration, which allows for intraoperative harvesting for immediate use of cells intra-operatively, supported by an analysis of mononuclear cell yields and osteogenic differentiation potential. A core focus of the thesis is the exploration of the human skeletal stem cell (hSSC) as a potential superior alternative to mesenchymal stromal cells (MSCs) in bone tissue engineering and this is explored in Chapter 13. We discuss the identification and characterization of hSSCs, their role in skeletal repair, and their potential applications in improving spinal fusion outcomes.

The thesis aims to bridge clinical practice with pathophysiology, emphasizing the role of skeletal stem cells in advancing spinal fusion techniques. By addressing current diagnostic challenges and introducing innovative surgical approaches, the thesis offers excitement for the future adoption of SSC-based therapies to improve patient outcomes, particularly in the context of an aging population.