Granulocyte-CSF links destructive inflammation and comorbidities in obstructive lung disease.

Chronic obstructive pulmonary disease (COPD) is an incurable inflammatory lung disease that afflicts millions of people worldwide, and it is the fourth leading cause of death. Systemic comorbidities affecting the heart, skeletal muscle, bone, and metabolism are major contributors to morbidity and mortality. Given the surprising finding in large prospective clinical biomarker studies that peripheral white blood cell count is more closely associated with disease than inflammatory biomarkers, we probed the role of blood growth factors.

Creating Interactions between Tissue-Engineered Skeletal Muscle and the Peripheral Nervous System.

Effective models of mammalian tissues must allow and encourage physiologically (mimetic) correct interactions between co-cultured cell types in order to produce culture microenvironments as similar as possible to those that would normally occur in vivo. In the case of skeletal muscle, the development of such a culture model, integrating multiple relevant cell types within a biomimetic scaffold, would be of significant benefit for investigations into the development, functional performance, and pathophysiology of skeletal muscle tissue. Although some work has been published regarding the behaviour of in vitro muscle models co-cultured with organotypic slices of CNS tissue or with stem cell-derived neurospheres, little investigation has so far been made regarding the potential to maintain isolated motor neurons within a 3D biomimetic skeletal muscle culture platform.

Emerging therapies for the treatment of skeletal muscle wasting in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that constitutes a major global health burden. A significant proportion of patients experience skeletal muscle wasting and loss of strength as a comorbidity of their COPD, a condition that severely impacts on their quality of life and survival. At present, the lung pathology is considered to be largely irreversible; however, the inherent adaptability of muscle tissue offers therapeutic opportunities to tackle muscle wasting and potentially reverse or delay the progression of this aspect of the disease, to improve patients' quality of life.

Serum Amyloid A Induces Toll-Like Receptor 2-Dependent Inflammatory Cytokine Expression and Atrophy in C2C12 Skeletal Muscle Myotubes.

Background: Skeletal muscle wasting is an important comorbidity of Chronic Obstructive Pulmonary Disease (COPD) and is strongly correlated with morbidity and mortality. Patients who experience frequent acute exacerbations of COPD (AECOPD) have more severe muscle wasting and reduced recovery of muscle mass and function after each exacerbation. Serum levels of the pro-inflammatory acute phase protein Serum Amyloid A (SAA) can rise more than 1000-fold in AECOPD and are predictively correlated with exacerbation severity.

Neuromuscular Junction Formation in Tissue-Engineered Skeletal Muscle Augments Contractile Function and Improves Cytoskeletal Organization.

Neuromuscular and neurodegenerative diseases are conditions that affect both motor neurons and the underlying skeletal muscle tissue. At present, the majority of neuromuscular research utilizes animal models and there is a growing need to develop novel methodologies that can be used to help understand and develop treatments for these diseases. Skeletal muscle tissue-engineered constructs exhibit many of the characteristics of the native tissue such as accurate fascicular structure and generation of active contractions.

Factors affecting the structure and maturation of human tissue engineered skeletal muscle.

Tissue engineered skeletal muscle has great utility in experimental studies of physiology, clinical testing and its potential for transplantation to replace damaged tissue. Despite recent work in rodent tissue or cell lines, there is a paucity of literature concerned with the culture of human muscle derived cells (MDCs) in engineered constructs. Here we aimed to tissue engineer for the first time in the literature human skeletal muscle in self-assembling fibrin hydrogels and determine the effect of MDC seeding density and myogenic proportion on the structure and maturation of the constructs.