Translational research : the journal of laboratory and clinical medicine
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Tendon injuries are common and can dramatically impair patient mobility and productivity, resulting in a significant socioeconomic burden and reduced quality of life. Because the tendon healing process results in the formation of a fibrotic scar, injured tendons never regain the mechanical strength of the uninjured tendon, leading to frequent reinjury. Many tendons are also prone to the development of peritendinous adhesions and excess scar formation, which further reduce tendon function and lead to chronic complications. ⋯ In addition, we examine the mechanisms through which different cell populations contribute to the fibrotic response to tendon injury, and how these responses can be affected by systemic factors and comorbidities. We then discuss gaps in our current understanding of tendon fibrosis and highlight how new technologies and research areas are shedding light on this clinically important and intractable challenge. A better understanding of the complex cellular environment during tendon healing is crucial to the development of new therapies to prevent fibrosis and promote tissue regeneration.
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Secondary lymphedema is a common complication of cancer treatment resulting in progressive fibroadipose tissue deposition, increased risk of infections, and, in rare cases, secondary malignancies. Until recently, the pathophysiology of secondary lymphedema was thought to be related to impaired collateral lymphatic formation after surgical injury. ⋯ In this review, we will discuss the evidence supporting this hypothesis and summarize recent publications demonstrating that lymphatic injury activates chronic immune responses that promote fibrosis and lymphatic leakiness, decrease collecting lymphatic pumping, and impair collateral lymphatic formation. We will review how chronic mixed T-helper cell inflammatory reactions regulate this process and how this response may be used to design novel therapies for lymphedema.
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Review
Noninvasive assessment of renal fibrosis by magnetic resonance imaging and ultrasound techniques.
Renal fibrosis is a useful biomarker for diagnosis and guidance of therapeutic interventions of chronic kidney disease (CKD), a worldwide disease that affects more than 10% of the population and is one of the major causes of death. Currently, tissue biopsy is the gold standard for assessment of renal fibrosis. However, it is invasive, and prone to sampling error and observer variability, and may also result in complications. ⋯ Promising findings have been reported in both preclinical and clinical studies using these techniques. Nevertheless, limited specificity, sensitivity, and practicality in these techniques may hinder their immediate application in clinical routine. In this review, we will introduce methodologies of these techniques, outline their applications in fibrosis imaging, and discuss their limitations and pitfalls.
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Cancer-associated fibrosis is a critical component of the tumor microenvironment (TME) which significantly impacts cancer behavior. However, there is significant controversy regarding fibrosis as a predominantly tumor promoting or tumor suppressing factor. Cells essential to the generation of tissue fibrosis such as fibroblasts and mesenchymal stem cells (MSCs) have dual phenotypes dependent upon their independence or association with cancer cells. ⋯ Third, there are subtypes of fibrosis which have unique function to support or inhibit cancer growth. Fourth, depleting fibrosis influences other TME components which drive the cancer response. Collectively, this review highlights the complexity of cancer-associated fibrosis and supports a dual function of fibrosis which evolves during the continuum of cancer growth.
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Cardiovascular disease is a leading cause of mortality in the world and is exacerbated by the presence of cardiac fibrosis, defined by the accumulation of noncontractile extracellular matrix proteins. Cardiac fibrosis is directly linked to cardiac dysfunction and increased risk of arrhythmia. Despite its prevalence, there is a lack of efficacious therapies for inhibiting or reversing cardiac fibrosis, largely due to the complexity of the cell types and signaling pathways involved. ⋯ Significant advances in cell transplantation therapy and biomaterials engineering have also demonstrated potential in regenerating the myocardium. Novel techniques, such as cellular direct reprogramming, and molecular targets, such as noncoding RNAs and epigenetic modifiers, are uncovering novel therapeutic options targeting fibrosis. This review provides an overview of current approaches and discuss future directions for treating cardiac fibrosis.