Lymphatic Vessel Network Structure and Physiology.

The lymphatic system is comprised of a network of vessels interrelated with lymphoid tissue, which has the holistic function to maintain the local physiologic environment for every cell in all tissues of the body. The lymphatic system maintains extracellular fluid homeostasis favorable for optimal tissue function, removing substances that arise due to metabolism or cell death, and optimizing immunity against bacteria, viruses, parasites, and other antigens. This article provides a comprehensive review of important findings over the past century along with recent advances in the understanding of the anatomy and physiology of lymphatic vessels, including tissue/organ specificity, development, mechanisms of lymph formation and transport, lymphangiogenesis, and the roles of lymphatics in disease.

Aging is associated with impaired angiogenesis, but normal microvascular network structure, in the rat mesentery.

Unlabelled: A big problem associated with aging is thought to be impaired microvascular growth or angiogenesis. However, to link the evidence for impaired angiogenesis to microvascular dysfunction in aged tissues, we must compare adult vs. aged microvascular networks in unstimulated scenarios.

Lysophosphatidic acid does not cause blood/lymphatic vessel plasticity in the rat mesentery culture model.

Understanding the mechanisms behind endothelial cell identity is crucial for the goal of manipulating microvascular networks. Lysophosphatidic acid (LPA) and serum stimulation have been suggested to induce a lymphatic identity in blood endothelial cells in vitro. The objective of this study was to determine if LPA or serum induces blood-to-lymphatic vessel phenotypic transition in microvascular networks.

Estimation of the Pressure Drop Required for Lymph Flow through Initial Lymphatic Networks.

Background: Lymphatic function is critical for maintaining interstitial fluid balance and is linked to multiple pathological conditions. While smooth muscle contractile mechanisms responsible for fluid flow through collecting lymphatic vessels are well studied, how fluid flows into and through initial lymphatic networks remains poorly understood. The objective of this study was to estimate the pressure difference needed for flow through an intact initial lymphatic network.

Printing cancer cells into intact microvascular networks: a model for investigating cancer cell dynamics during angiogenesis.

While cancer cell invasion and metastasis are dependent on cancer cell-stroma, cancer cell-blood vessel, and cancer cell-lymphatic vessel interactions, our understanding of these interactions remain largely unknown. A need exists for physiologically-relevant models that more closely mimic the complexity of cancer cell dynamics in a real tissue environment. The objective of this study was to combine laser-based cell printing and tissue culture methods to create a novel ex vivo model in which cancer cell dynamics can be tracked during angiogenesis in an intact microvascular network.

Applications of computational models to better understand microvascular remodelling: a focus on biomechanical integration across scales.

Microvascular network remodelling is a common denominator for multiple pathologies and involves both angiogenesis, defined as the sprouting of new capillaries, and network patterning associated with the organization and connectivity of existing vessels. Much of what we know about microvascular remodelling at the network, cellular and molecular scales has been derived from reductionist biological experiments, yet what happens when the experiments provide incomplete (or only qualitative) information? This review will emphasize the value of applying computational approaches to advance our understanding of the underlying mechanisms and effects of microvascular remodelling. Examples of individual computational models applied to each of the scales will highlight the potential of answering specific questions that cannot be answered using typical biological experimentation alone.

Pericyte dynamics during angiogenesis: new insights from new identities.

Therapies aimed at manipulating the microcirculation require the ability to control angiogenesis, defined as the sprouting of new capillaries from existing vessels. Blocking angiogenesis would be beneficial in many pathologies (e.g.

VEGF-C induces lymphangiogenesis and angiogenesis in the rat mesentery culture model.

Objective: Lymphatic and blood microvascular systems are critical for tissue function. Insights into the coordination of both systems can be gained by investigating the relationships between lymphangiogenesis and angiogenesis. Recently, our laboratory established the rat mesentery culture model as a novel tool to investigate multicellular interactions during angiogenesis in an intact microvascular network scenario.

Vascular islands during microvascular regression and regrowth in adult networks.

Objective: Angiogenesis is the growth of new vessels from pre-existing vessels and commonly associated with two modes: capillary sprouting and capillary splitting. Previous work by our laboratory suggests vascular island incorporation might be another endothelial cell dynamic involved in microvascular remodeling. Vascular islands are defined as endothelial cell segments disconnected from nearby networks, but their origin remains unclear.

Relationships between lymphangiogenesis and angiogenesis during inflammation in rat mesentery microvascular networks.

Background: Lymphatic and blood microvascular systems play a coordinated role in the regulation of interstitial fluid balance and immune cell trafficking during inflammation. The objective of this study was to characterize the temporal and spatial relationships between lymphatic and blood vessel growth in the adult rat mesentery following an inflammatory stimulus.

Methods And Results: Mesenteric tissues were harvested from unstimulated adult male Wistar rats and at 3, 10, and 30 days post compound 48/80 stimulation.

Cell proliferation along vascular islands during microvascular network growth.

Background: Observations in our laboratory provide evidence of vascular islands, defined as disconnected endothelial cell segments, in the adult microcirculation. The objective of this study was to determine if vascular islands are involved in angiogenesis during microvascular network growth.

Results: Mesenteric tissues, which allow visualization of entire microvascular networks at a single cell level, were harvested from unstimulated adult male Wistar rats and Wistar rats 3 and 10 days post angiogenesis stimulation by mast cell degranulation with compound 48/80.