Publications by authors named "Haglund L"

Background: Extracellular vesicles (EVs) function as biomarkers and are crucial in cell communication and regulation, with therapeutic potential for intervertebral disc (IVD)-related low back pain (LBP). EV cargo is often affected by tissue health, which may affect the therapeutic potential. There is currently limited knowledge of how the cargo of IVD cell-derived EVs varies with tissue health and how differences in proteomic profile affect the predicted biological functions.

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Cellular senescence, characterized by a permanent state of cell cycle arrest and a secretory phenotype contributing to inflammation and tissue deterioration, has emerged as a target for age-related interventions. Accumulation of senescent cells is closely linked with intervertebral disc (IVD) degeneration, a prevalent age-dependent chronic disorder causing low back pain. Previous studies have highlighted that platelet-derived growth factor (PDGF) mitigated IVD degeneration through anti-apoptosis, anti-inflammation, and pro-anabolism.

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Intervertebral disc (IVD) herniation is a leading cause of disability and lower back pain, causing enormous socioeconomic burdens. The standard of care for disc herniation is nucleotomy, which alleviates pain but does not repair the annulus fibrosus (AF) defect nor recover the biomechanical function of the disc. Existing bioadhesives for AF repair are limited by insufficient adhesion and significant mechanical and geometrical mismatch with the AF tissue, resulting in the recurrence of protrusion or detachment of bioadhesives.

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Purpose: Pain is an understudied physiological effect of spaceflight. Changes in inflammatory and tissue degradation markers are often associated with painful conditions. Our aim was to evaluate the changes in markers associated with tissue deterioration after a short-term spaceflight.

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Academic researchers faced a multitude of challenges posed by the COVID-19 pandemic, including widespread shelter-in-place orders, workplace closures, and cessation of in-person meetings and laboratory activities. The extent to which these challenges impacted musculoskeletal researchers, specifically, is unknown. We developed an anonymous web-based survey to determine the pandemic's impact on research productivity and career prospects among musculoskeletal research trainees and faculty.

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Low back pain is a leading cause of disability worldwide, often attributed to intervertebral disc (IVD) degeneration with loss of the functional nucleus pulposus (NP). Regenerative strategies utilizing biomaterials and stem cells are promising for NP repair. Human NP tissue is highly viscoelastic, relaxing stress rapidly under deformation.

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Toll-like receptors (TLRs) are key mediators of inflammation in intervertebral disc (IVD) degeneration. TLR-2 activation contributes to the degenerative process by increasing the expression of extracellular matrix-degrading enzymes, pro-inflammatory cytokines, and neurotrophins. As potent post-transcriptional regulators, microRNAs can modulate intracellular mechanisms, and their dysregulation is known to contribute to numerous pathologies.

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Low back pain resulting from disc degeneration is a leading cause of disability worldwide. However, to date few therapies target the cause and fail to repair the intervertebral disc (IVD). This study investigates the ability of an injectable hydrogel (NPgel), to inhibit catabolic protein expression and promote matrix expression in human nucleus pulposus (NP) cells within a tissue explant culture model isolated from degenerate discs.

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Article Synopsis
  • Macrophages in dorsal root ganglia (DRG) are traditionally studied for their roles in pain and nerve injury, but they also monitor blood vessels by sampling macromolecules from the bloodstream.
  • The vasculature in the DRG has unique properties that change along the arteriovenous axis, and macrophages interact with this specialized endothelial structure, which is influenced by their ability to engulf materials and regulate blood vessel permeability.
  • Two types of perivascular macrophages were identified in the DRG: CD163+ macrophages, which are locally maintained, play a crucial role in monitoring blood vessels, and respond differently to inflammation, highlighting a new understanding of macrophages in the neurovascular environment.
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  • Low back pain, linked to intervertebral disc degeneration, may be treatable with senolytic drugs o-Vanillin and RG-7112, which target aging cells in these discs.
  • A study tested these drugs individually and in combination on cells from degenerated human IVDs, revealing that the combination was more effective at reducing senescent cells and inflammatory factors.
  • The results suggest that using both drugs together could be a promising new approach to treating low back pain associated with IVD degeneration.
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Bone tissue engineering using stem cells to build bone directly on a scaffold matrix often fails due to lack of oxygen at the injury site. This may be avoided by following the endochondral ossification route; herein, a cartilage template is promoted first, which can survive hypoxic environments, followed by its hypertrophy and ossification. However, hypertrophy is so far only achieved using biological factors.

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Purpose: Bullying, harassment, and discrimination (BHD) are prevalent in academic, scientific, and clinical departments, particularly orthopedic surgery, and can have lasting effects on victims. As it is unclear how BHD affects musculoskeletal (MSK) researchers, the following study assessed BHD in the MSK research community and whether the COVID-19 pandemic, which caused hardships in other industries, had an impact.

Methods: A web-based anonymous survey was developed in English by ORS Spine Section members to assess the impact of COVID-19 on MSK researchers in North America, Europe, and Asia, which included questions to evaluate the personal experience of researchers regarding BHD.

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Background: In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab-to-lab variability jeopardizes the much-needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources.

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Objective: Facet joints are crucial for spinal stability but develop premature osteoarthritis in patients with adolescent idiopathic scoliosis (AIS). Here, we evaluated the association between facet joint cartilage and subchondral bone homeostasis, perceived back pain and 3-dimensional spinal deformity to better understand the role of facet joint degeneration in AIS progression and pain.

Method: The osteoarthritic state of cartilage and bone of AIS facet joint surgical samples were characterized using histological OARSI scoring, visual morphological grading and μCT analysis, respectively.

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Transferring fibromyalgia patient immunoglobulin G (IgG) to mice induces pain-like behaviour, and fibromyalgia IgG binds mouse and human satellite glia cells (SGCs). These findings suggest that autoantibodies could be part of fibromyalgia pathology. However, it is unknown how frequently fibromyalgia patients have anti-SGC antibodies and how anti-SGC antibodies associate with disease severity.

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Intervertebral disc (IVD) degeneration and herniation often necessitate surgical interventions including a discectomy with or without a nucleotomy, which results in a loss of the normal nucleus pulposus (NP) and a defect in the annulus fibrosus (AF). Due to the limited regenerative capacity of the IVD tissue, the annular tear may remain a persistent defect and result in recurrent herniation post-surgery. Bioadhesives are promising alternatives but show limited adhesion performance, low regenerative capacity, and inability to prevent re-herniation.

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Article Synopsis
  • Intervertebral disc degeneration is a major contributor to low back pain and necessitates effective preclinical research models to improve treatments.
  • Both in vivo animal models and ex vivo organ culture models are commonly used, but each has its own strengths and weaknesses, leading to ongoing debates among researchers.
  • Experts, through a literature review, emphasize that using a combination of various models may yield the best research outcomes by capitalizing on the unique benefits of each approach.
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Human mesenchymal stem cell (hMSC) and extracellular vesicle (EV) therapy is a promising treatment for discogenic low back pain (LBP). Although promising, major obstacles remain to be overcome. Cellular senescence reduces self-renewal and multipotent potentials, and the senescence-associated secretory phenotype creates an inflammatory environment negatively affecting tissue homeostasis.

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Background: During the intervertebral disc (IVD) degeneration process, initial degenerative events occur at the extracellular matrix level, with the appearance of neoepitope peptides formed by the cleavage of aggrecan and collagen. This study aims to elucidate the spatial and temporal alterations of aggrecan and collagen neoepitope level during IVD degeneration.

Methods: Bovine caudal IVDs were cultured under four different conditions to mimic different degenerative situations.

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Article Synopsis
  • Single-cell RNA sequencing revealed that mature oligodendrocytes (MOLs) in the human brain and spinal cord have distinct subpopulations based on region and age.
  • Spinal cord MOLs showed increased immune-related markers, while subventricular zone MOLs had more development-linked transcription factors, indicating unique characteristics across different brain regions.
  • Pediatric MOLs, particularly those from children under 5, exhibited higher expression of genes related to development and immune activity, suggesting that younger MOLs are influenced by both developmental and environmental factors.
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In this study, we used single-cell transcriptomic analysis to identify new specific biomarkers for nucleus pulposus (NP) and inner annulus fibrosis (iAF) cells, and to define cell populations within non-degenerating (nD) and degenerating (D) human intervertebral discs (IVD) of the same individual. Cluster analysis based on differential gene expression delineated 14 cell clusters. Gene expression profiles at single-cell resolution revealed the potential functional differences linked to degeneration, and among NP and iAF subpopulations.

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Article Synopsis
  • * Researchers used single-cell RNA sequencing to discover that nerve injury creates a specific inflammatory microglia subtype in males, resulting in greater microglial proliferation compared to females.
  • * The findings highlight the gene Apolipoprotein E (Apoe) as being significantly upregulated in chronic pain scenarios and link variations in the human APOE gene to chronic pain, revealing a common disease-related microglial subpopulation in both mice and humans.
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Background: The need to support a healthy lifestyle among the population has become increasingly apparent in recent years. The National Board of Health and Welfare in Sweden has published national guidelines regarding unhealthy lifestyle habits since 2011. An instrument based on the practical and theoretical foundations of occupational therapy was developed to support the profession's unique contribution to implementing these guidelines.

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Background: Good clinical research is often conducted in close collaboration between patients, the public, and researchers. Few studies have reported the development of patient and public involvement (PPI) in research outside the United States and the United Kingdom, and for patients with more aggressive cancers. The study aimed to describe and evaluate the development of PPI in oesophageal cancer survivorship research in Sweden by the use of a framework to support the process.

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Orthopedic tumor resection, trauma, or degenerative disease surgeries can result in large bone defects and often require bone grafting. However, standard autologous bone grafting has been associated with donor site morbidity and/or limited quantity. As an alternate, allografts with or without metallic or polyether-etherketone have been used as grafting substitutes.

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