Laboratory models for the investigation of lymphangiomatosis
Introduction
Lymphangiomatosis is an uncommon proliferative disorder of the lymphatic vasculature, whose etiology remains poorly understood. This disease spectrum affects a patient population that is small in number, but the consequences of this pathology are potentially devastating (Rockson, 2011b). The disease can be considered a failure of normal lymphatic development (Gordon and Mortimer, 2011, Lee et al., 2005). Sites of involvement can include soft tissue, viscera, and bone (Gordon and Mortimer, 2011, Venkatramani et al., 2011). Visceral involvement carries a particularly poor prognosis. Furthermore, lymphangiomatosis can be limited to a defined organ-delimited structure (e.g., spleen, liver, and thoracic cavity) or can reflect a more generalized process (Blei, 2011).
Section snippets
The spectrum of human clinical lymphangiomatosis
The lymphangiomatosis spectrum encompasses a remarkable heterogeneity in its potential presentation. These various features should be considered in attempts to recapitulate the human pathology in suitable animal models of disease.
Isolated lymphatic malformations, also known as lymphangiomas, are low-flow vascular malformations (Perkins et al., 2010). Seventy-five percent of these lesions occur in the head and neck region. The clinical presentation is related to the size of the malformation and
Clinical therapeutic observations
Conventional non-surgical options for patients with lymphangiomatosis have been limited. In isolated cases or limited case series, some disease stabilization has been accomplished through treatment with pegylated (PEG) interferons, glucocorticoids, tyrosine kinase inhibitors, and, in the case of bony involvement, biphosponates (Ozeki et al., 2007). Of late, there has been growing enthusiasm for newer molecular interventions that have the potential for improving the outcome of these often
Three-dimensional lymphatic ring assay
This is a model that attempts to recapitulate in vivo findings within an in vitro model of lymphangiogenesis. The lymphatic ring assay recapitulates the different steps of cell sprouting from a pre-existing lymphatic vessel in a collagen environment (Bruyere et al., 2008). Thoracic ducts used for lymphatic ring cultures were collected from male and female C57BL/6 mice and 3-dimensional lymphatic ring cultures are undertaken. The ring-shaped explants embedded in rat tail interstitial collagen-I
Lymphangiomatosis is part of the lymphatic continuum
Despite the continued absence of an ideal laboratory model for lymphangiomatosis, it is apparent that lymphatic maldevelopment is central to the pathogenesis of the disorder. Thus, it is plausible to imagine that laboratory investigation of lymphangiomatosis will be the beneficiary, directly or indirectly, of the remarkable insights into the mechanisms of lymphangiogenesis that continue to expand and to be translated into therapeutic approaches to lymphatic pathology (Zheng et al., 2014).
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Allan and Tina Neill Professor of Lymphatic Research and Medicine.