Current Pathobiology Reports最新文献

Purpose of review: Stem cells have been proposed as sources for tissue replacement when healing does not occur. These cells could contribute directly to skin structures via differentiation, or via producing trophic factors that would 'educate' the micro-environment to encourage tissue repair. Studies in animals have supported both mechanisms, but translation to humans has been challenged by poor cell survival after transplantation. However, the improvement noted with even transient existence suggests another new possibility, that of suppressing the inflammatory response that limits regenerative healing. Herein, we will propose that this immunomodulatory aspect holds promise for promoting skin healing.

Recent findings: We have found that stem cell transplantation into wounds can dampen both acute and chronic inflammation, leading to more regenerative-like healing and diminished scarring.

Summary: Wound healing could be improved by dampening inflammation both initially to allow for tissue replacement to proceed and late to reduce scarring.

Purpose of review: Orthopaedic trauma is a major cause of morbidity and mortality worldwide. Although many fractures tend to heal if treated appropriately either by nonoperative or operative methods, delayed or failed healing, as well as infections, can lead to devastating complications. Tissue engineering is an exciting, emerging field with much scientific and clinical relevance in potentially overcoming the current limitations in the treatment of orthopaedic injuries.

Recent findings: While direct translation of bone tissue engineering technologies to clinical use remains challenging, considerable research has been done in studying how cells, scaffolds, and signals may be used to enhance acute fracture healing and to address the problematic scenarios of nonunion and critical-sized bone defects. Taken together, the research findings suggest that tissue engineering may be considered to stimulate angiogenesis and osteogenesis, to modulate the immune response to fractures, to improve the biocompatibility of implants, to prevent or combat infection, and to fill large gaps created by traumatic bone loss. The abundance of preclinical data supports the high potential of bone tissue engineering for clinical application, although a number of barriers to translation must first be overcome.

Summary: This review focuses on the current and potential applications of bone tissue engineering approaches in orthopaedic trauma with specific attention paid to acute fracture healing, nonunion, and critical-sized bone defects.

Microbial metabolites influence the function of epithelial, endothelial and immune cells in the intestinal mucosa. Microbial metabolites like SCFAs and B complex vitamins direct macrophage polarization whereas microbial derived biogenic amines modulate intestinal epithelium and immune response. Aberrant bacterial lipopolysaccharide-mediated signaling may be involved in the pathogenesis of chronic intestinal inflammation and colorectal carcinogenesis. Our perception of human microbes has changed from that of opportunistic pathogens to active participants maintaining intestinal and whole body homeostasis. This review attempts to explain the dynamic and enriched interactions between the intestinal epithelial mucosa and commensal bacteria in homeostasis maintenance.

Purpose of review: This review will explore the contribution of IELs to mucosal innate immunity and highlight the similarities in IEL functional responses to bacteria, viruses and protozoan parasite invasion.

Recent findings: IELs rapidly respond to microbial invasion by activating host defense responses, including the production of mucus and antimicrobial peptides to prevent microbes from reaching the epithelial surface. During active infection, IELs promote epithelial cytolysis, cytokine and chemokine production to limit pathogen invasion, replication and dissemination. Commensal-induced priming of IEL effector function or continuous surveillance of the epithelium may be important contributing factors to the rapidity of response.

Summary: Impaired microbial recognition, dysregulated innate immune signaling or microbial dysbiosis may limit the protective function of IELs and increase susceptibility to disease. Further understanding of the mechanisms regulating IEL surveillance and sentinel function may provide insight into the development of more effective targeted therapies designed to reinforce the mucosal barrier.

Purpose of review: Myofibroblasts are the fundamental drivers of fibrosing disorders; there is great value in better defining epigenetic networks involved in myofibroblast behavior. Complex epigenetic paradigms, which are likely organ and/or disease specific, direct pathologic myofibroblast phenotypes. In this review, we highlight epigenetic regulators and the mechanisms through which they shape myofibroblast phenotype in fibrotic diseases of different organs.

Recent findings: Hundreds of genes and their expression contribute to the myofibroblast transcriptional regime influencing myofibroblast phenotype. An increasingly large number of epigenetic modifications have been identified in the regulation of these signaling pathways driving myofibroblast activation and disease progression. Drugs that inhibit or reverse profibrotic epigenetic modifications have shown promise in vitro and in vivo; however, no current epigenetic therapies have been approved to treat fibrosis. Newly described epigenetic mechanisms will be mentioned, along with potential therapeutic targets and innovative strategies to further understand myofibroblast-directed fibrosis.

Summary: Epigenetic regulators that direct myofibroblast behavior and differentiation into pathologic myofibroblast phenotypes in fibrotic disorders comprise both overlapping and organ-specific epigenetic mechanisms.