The Use of MSCs, iPSCs, and EVs in the Repair of Human MSK Tissues: Is Ultimate Success Dependent on Developing Excellent Implant Materials as Well as Creating an Optimal Environment for Implantation? What Is the Rationale for These Choices?

It has been >35 years since the cells described as mesenchymal stem cells (MSCs) were reported to have multi-lineage potential, which opened the possibility that they could be used to repair injured or diseased musculoskeletal tissues. Since that time, similar cells have been isolated from many tissues, again raising expectations that they could be used to repair or regenerate many types of tissues. While some progress in using these cells, as well as induced pluripotent stem cells (iPSCs), to facilitate the repair of tissues has been achieved, an emerging body of literature would suggest that the cells in question facilitate repair via released extracellular vesicles (EVs) that contain a cargo of molecules which induce endogenous cells to do the actual repair.

Skeletal Muscle Composition and the Effects of Exercise and/or Prebiotic Fiber in Preventing Diet Related Morbidities.

We established a model of diet-induced obesity in Sprague-Dawley rats that produces, in addition to obesity, metabolic syndrome and musculoskeletal degeneration. Prebiotic fiber and aerobic exercise interventions have been shown to rescue bones and joints from degeneration, but it has yet to be shown if muscle degeneration can also be stopped with these interventions. This study was aimed at determining if prebiotic fiber supplementation and/or aerobic exercise can prevent muscular alterations in our rat model of obesity.

Freezing negatively impacts the interlamellar mechanical properties of the degenerated human annulus fibrosus.

Mechanical testing of biological tissues often utilizes previously frozen samples but there are conflicting reports about the impact of freezing on mechanical properties. There are no current studies examining the impact of freezing on the interlamellar matrix in the annulus fibrosus of intervertebral disc. We quantified the freezing-induced changes in the interlamellar mechanical properties of degenerated human and non-degenerated bovine annulus fibrosus tissues.

Human Disc Degeneration Is Accompanied by a Loss of Anterior Annulus Fibrosus Interlamellar Matrix Integrity as Assessed by Peel Tests.

Introduction: Disc degeneration (DD) is accompanied by biomechanical changes in the intervertebral discs. The lamellae of the annulus fibrosus (AF) are interconnected through the interlamellar matrix (ILM). The ILM contains interlamellar cross-bridges, connecting the lamellae radially in three dimensions.

From fluctuations to stability: In-Situ chondrocyte response to cyclic compressive loading.

Chondrocytes, the sole cellular components in articular cartilage, are mechanosensitive and undergo significant morphological and volumetric changes in response to mechanical loading. These changes activate ion channels, initiating cellular mechanotransduction processes crucial for maintaining cartilage health. Dynamic loading has been shown to elicit anabolic responses that preserve cartilage integrity, while prolonged mechanical unloading leads to atrophy.

Systematic Review of Relevant Biomarkers for Human Connective Tissue Repair and Healing Outcome: Implications for Understanding Healing Processes and Design of Healing Interventions.

The healing process following connective tissue (CT) injuries is complex, resulting in variable and often suboptimal outcomes. Patients undergoing CT repair frequently experience healing failures, compromised function, and chronic degenerative diseases. The identification of biomarkers to guide improved clinical outcomes after CT injuries remains an emerging but promising field.

Novel tissue biomarker candidates to predict both deep venous thrombosis and healing outcome after Achilles tendon rupture.

Deep venous thrombosis (DVT) and poor long-term patient outcomes frequently occur in patients with Achilles tendon rupture (ATR). Biomarkers for DVT and their possible relationship to long-term healing outcomes remain unexplored. To identify DVT biomarkers from proteomic profiles during the inflammatory and proliferative healing stages and assess their associations with one-year healing outcomes after surgical repair of ATR.

Regulation of Joint Tissues and Joint Function: Is There Potential for Lessons to Be Learned Regarding Regulatory Control from Joint Hypermobility Syndromes?

Normal development of joints starts in utero with the establishment of a cellular and extracellular matrix template. Following birth, individual joint tissues grow and mature in response to biochemical and mechanical signals, leading to a coordinated pattern of further maturation resulting in a joint that functions as an organ system. Each joint develops and matures as an organ system defined by the biomechanical environment in which it will function.

Sex-specific response of intramuscular fat to diet-induced obesity in rats.

Metabolic abnormalities associated with excess adiposity in obesity contribute to many noncommunicable diseases, including sarcopenic obesity. Sarcopenic obesity is the loss of muscle mass coupled with excess fat mass and fatty infiltrations in muscle tissue called myosteatosis. A diet-induced obesity model was developed to study fat infiltration in muscle tissue.

Costs of physician and diagnostic imaging services for shoulder, knee, and low back pain conditions: A population-based study in Alberta, Canada.

Objectives: To 1) estimate the utilization and costs of physician and diagnostic imaging (DI) services for shoulder, knee, and low-back pain (LBP) conditions; and 2) examine determinants of the utilization and costs of these services.

Methods: All patients visiting a physician for shoulder, knee, or LBP conditions (identified by the ICD-9 codes) in Alberta, Canada, in fiscal year (FY) 2022/2023 were included. Interested outcomes included numbers and costs of physician visits and DI exams stratified by condition, physician specialty, DI modality, and patients' sex and age.

Development of shoulder osteoarthritis and bone lesions in female and male rats subjected to a high fat/sucrose diet.

Oligofructose prebiotic fiber supplementation has been reported to mitigate the effects of a high fat/high sucrose diet and reduce knee joint degeneration in male rats. However, few studies investigated the development of osteoarthritis and bone lesions as a function of sex and in joints other than the knee. This study was aimed at to quantifying the effect of a HFS diet and prebiotic fiber supplementation on shoulder joint health in male and female Sprague-Dawley rats.

A novel scoring system to separate typical OA joint degeneration from non-typical lesions in male rats.

Objective: To develop a novel scoring system to characterize osteoarthritis-related degeneration distinct from spontaneous subchondral bone lesions observed in the tibia and femur of male Sprague Dawley rats.

Method: Knee joints from male rats following 12 weeks of a diet-induced obesity model of osteoarthritis (OA) were assessed. OA histopathological changes (OAHC) were assessed in the knee joints.

Lithium Ions as Modulators of Complex Biological Processes: The Conundrum of Multiple Targets, Responsiveness and Non-Responsiveness, and the Potential to Prevent or Correct Dysregulation of Systems during Aging and in Disease.

Lithium is one of the lightest elements on Earth and it has been in the environment since the formation of the galaxy. While a common element, it has not been found to be an essential element in biological processes, ranging from single cell organisms to . Instead, at an early stage of evolution, organisms committed to a range of elements such as sodium, potassium, calcium, magnesium, zinc, and iron to serve essential functions.

Collagen integrity of the annulus fibrosus in degenerative disc disease individuals quantified with collagen hybridizing peptide.

Introduction: Degenerative disc disease (DDD) is accompanied by structural changes in the intervertebral discs (IVD). Extra-cellular matrix degradation of the annulus fibrosus (AF) has been linked with degeneration of the IVD. Collagen is a vital component of the IVD.

Participants' perceived benefits from the GLA:D™ program for individuals living with hip and knee osteoarthritis: a qualitative study.

Background: The Good Life with osteoArthritis: Denmark (GLA:D™), an evidence-based education and exercise program designed for conservative management of knee and hip osteoarthritis (OA), has been shown to benefit participants by reducing pain, improving function, and quality of life. Standardized reporting in the GLA:D databases enabled the measurement of self-reported and performance-based outcomes. There is a paucity of qualitative research on the participants' perceptions of this program, and it is important to understand whether participants' perceptions of the benefits of the program align with reported quantitative findings.

Chondrocyte deformation during the unloading phase of cyclic compression loading.

Cell volume and shape changes play a pivotal role in cellular mechanotransduction, governing cellular responses to external loading. Understanding the dynamics of cell behavior under loading conditions is essential to elucidate cell adaptation mechanisms in physiological and pathological contexts. In this study, we investigated the effects of dynamic cyclic compression loading on cell volume and shape changes, comparing them with static conditions.

Extracellular Vesicles Generated by Mesenchymal Stem Cells in Stirred Suspension Bioreactors Promote Angiogenesis in Human-Brain-Derived Endothelial Cells.

Interrupted blood flow in the brain due to ischemic injuries such as ischemic stroke or traumatic brain injury results in irreversible brain damage, leading to cognitive impairment associated with inflammation, disruption of the blood-brain barrier (BBB), and cell death. Since the BBB only allows entry to a small class of drugs, many drugs used to treat ischemia in other tissues have failed in brain-related disorders. The administration of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) has shown promise in improving the functional recovery of the brain following cerebral ischemia by inducing blood vessel formation.

The Heterogeneity of Post-Menopausal Disease Risk: Could the Basis for Why Only Subsets of Females Are Affected Be Due to a Reversible Epigenetic Modification System Associated with Puberty, Menstrual Cycles, Pregnancy and Lactation, and, Ultimately, Menopause?

For much of human evolution, the average lifespan was <40 years, due in part to disease, infant mortality, predators, food insecurity, and, for females, complications of childbirth. Thus, for much of evolution, many females did not reach the age of menopause (45-50 years of age) and it is mainly in the past several hundred years that the lifespan has been extended to >75 years, primarily due to public health advances, medical interventions, antibiotics, and nutrition. Therefore, the underlying biological mechanisms responsible for disease risk following menopause must have evolved during the complex processes leading to to serve functions in the pre-menopausal state.

Optimizing tendon repair and regeneration: how does the environment shape outcomes following rupture of a tendon such as the Achilles tendon?

Risk for rupture of the Achilles tendon, and other tendons increases with age. Such injuries of tissues that function in high load environments generally are believed to heal with variable outcome. However, in many cases, the healing does not lead to a good outcome and the patient cannot return to the previous level of participation in active living activities, including sports.

'I do hope more people can benefit from it.': The qualitative experience of individuals living with osteoarthritis who participated in the GLA:D™ program in Alberta, Canada.

Introduction: The Good Life with osteoArthritis: Denmark (GLA:DTM) is an evidence-based program designed for individuals with symptomatic hip and knee osteoarthritis (OA). This program has reported improvement in pain, quality of life and self-efficacy, as well as delays in joint replacement surgery for adults with moderate to severe hip or knee OA. Evaluations of GLA:DTM implementation in several countries have focused on effectiveness, training, and feasibility of the program primarily from the provider perspective.

Towards understanding how bisphosphonate-dependent alterations to nutrient canal integrity can contribute to risk for atypical femoral fractures: Biomechanical considerations and potential relationship to a real-world analogy.

Bisphosphonates are a class of drugs which have shown good efficacy in the treatment of post-menopausal osteoporosis, as well as a good safety profile. However, side-effects such as risk for atypical femoral fractures (AFF) have appeared, leading to a decline in use of the drugs by many patients who would benefit from the treatment. While patient characteristics have contributed to improved understanding of risk factors, the mechanisms involved that explain AFF risk have not appeared.