Current tissue microenvironment reports最新文献

Purpose of review: The contribution of biomechanical forces to hematopoietic stem cell (HSC) development in the embryo is a relatively nascent area of research. Herein, we address the biomechanics of the endothelial-to-hematopoietic transition (EHT), impact of force on organelles, and signaling triggered by extrinsic forces within the aorta-gonad-mesonephros (AGM), the primary site of HSC emergence.

Recent findings: Hemogenic endothelial cells undergo carefully orchestrated morphological adaptations during EHT. Moreover, expansion of the stem cell pool during embryogenesis requires HSC extravasation into the circulatory system and transit to the fetal liver, which is regulated by forces generated by blood flow. Findings from other cell types also suggest that forces external to the cell are sensed by the nucleus and mitochondria. Interactions between these organelles and the actin cytoskeleton dictate processes such as cell polarization, extrusion, division, survival, and differentiation.

Summary: Despite challenges of measuring and modeling biophysical cues in the embryonic HSC niche, the past decade has revealed critical roles for mechanotransduction in governing HSC fate decisions. Lessons learned from the study of the embryonic hematopoietic niche promise to provide critical insights that could be leveraged for improvement in HSC generation and expansion ex vivo.

Purpose of the review: This review aims to summarize the current knowledge of the extracellular matrix remodeling during hepatic fibrosis. We discuss the diverse interactions of the extracellular matrix with hepatic cells and the surrounding matrix in liver fibrosis, with the focus on the molecular pathways and the mechanisms that regulate extracellular matrix remodeling.

Recent findings: The extracellular matrix not only provides structure and support for the cells, but also controls cell behavior by providing adhesion signals and by acting as a reservoir of growth factors and cytokines.

Summary: Hepatic fibrosis is characterized by an excessive accumulation of extracellular matrix. During fibrogenesis, the natural remodeling process of the extracellular matrix varies, resulting in the excessive accumulation of its components, mainly collagens. Signals released by the extracellular matrix induce the activation of hepatic stellate cells, which are the major source of extracellular matrix and most abundant myofibroblasts in the liver.

Graphical abstract:

Purpose: The microvascular capillary network is ensheathed by cells called pericytes - a heterogeneous population of mural cells derived from multiple lineages. Pericytes play a multifaceted role in the body, including in vascular structure and permeability, regulation of local blood flow, immune and wound healing functions, induction of angiogenesis, and generation of various progenitor cells. Here, we consider the role of pericytes in capillary de-recruitment, a pathophysiologic phenomenon that is observed following hyperemic stimuli in the presence of a stenosis and attenuates the hyperemic response.

Recent findings: We discuss recent observations that conclusively demonstrate pericytes to be the cellular structures that contract in response to hyperemic stimuli when an upstream arterial stenosis is present. This response constricts capillaries, which is likely aimed at maintaining capillary hydrostatic pressure, an important factor in tissue homeostasis. Nonetheless, the ensuing attenuation of the hyperemic response can lead to a decrease in energy supply and negatively impact tissue health.

Summary: Therapeutics aimed at preventing pericyte-mediated capillary de-recruitment may prove beneficial in conditions such as coronary stenosis and peripheral arterial disease by reducing restriction in hyperemic flow. Identification of the pericyte subtypes involved in this de-recruitment and the underlying molecular mechanisms regulating this process will greatly assist this purpose.

Purpose of review: The tumor microenvironment (TME) is an amalgam of multiple dysregulated biophysical cues that can alter cellular behavior through mechanotransductive signaling and epigenetic modifications. Through this review, we seek to characterize the extent of biophysical and epigenetic regulation of cancer stemness and tumor-associated immune cells in order to identify ideal targets for cancer therapy.

Recent findings: Recent studies have identified cancer stemness and immune action as significant contributors to neoplastic disease, due to their susceptibility to microenvironmental influences. Matrix stiffening, altered vasculature, and resultant hypoxia within the TME can influence cancer stem cell (CSC) and immune cell behavior, as well as alter the epigenetic landscapes involved in cancer development.

Summary: This review highlights the importance of aberrant biophysical cues in driving cancer progression through altered behavior of CSCs and immune cells, which in turn sustains further biophysical dysregulation. We examine current and potential therapeutic approaches that break this self-sustaining cycle of disease progression by targeting the presented biophysical and epigenetic signatures of cancer. We also summarize strategies including the normalization of the TME, targeted drug delivery, and inhibition of cancer-enabling epigenetic players.

Purpose of review: Nonhealing wounds are a significant issue facing the healthcare industry. Materials that modulate the wound microenvironment have the potential to improve healing outcomes.

Recent findings: A variety of acellular and cellular scaffolds have been developed for regulating the wound microenvironment, including materials for controlled release of antimicrobials and growth factors, materials with inherent immunomodulative properties, and novel colloidal-based scaffolds. Scaffold construction methods include electrospinning, 3D printing, decellularization of extracellular matrix, or a combination of techniques. Material application methods include layering or injecting at the wound site.

Summary: Though these techniques show promise for repairing wounds, all material strategies thus far struggle to induce regeneration of features such as sweat glands and hair follicles. Nonetheless, innovative technologies currently in the research phase may facilitate future attainment of these features. Novel methods and materials are constantly arising for the development of microenvironments for enhanced wound healing.