Visualization of Lymphatic Vessel Development, Growth, and Function

Pollmann, Cathrin; Hägerling, René; Kiefer, Friedemann

doi:10.1007/978-3-7091-1646-3_13

Cited by 17 publications

(10 citation statements)

References 69 publications

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“…Da GATA2 eine essenzielle Rolle bei der Transkription einer Vielzahl von Genen, die an der Gefäßklappenmorphogenese beteiligt sind, spielt und somit bedeutend für die Morphogenese und Funktion der Lymphgefäßklappen ist [4,[7][8][9]14], sollten die Lymphgefäßklappen im Anschluss genauer untersucht werden.…”

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Light sheet microscopy-based 3-dimensional histopathology of the lymphatic vasculature in Emberger syndrome

Hägerling

2020

Phlebologie

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Introduction Lymphovascular diseases represent a heterogenous group of inherited and sporadic disorders and refer to a range of possible underlying pathologies and pathogenesis.Emberger Syndrome, an inherited form of lymphedema, is characterized by bilateral lower limb lymphedema, however, upper limbs do not show any signs of swelling.To identify disease-associated histopathological alterations in patients with Emberger Syndrome and to elucidate potential histological differences between the lymphatic vasculature of upper and lower limbs, a detailed knowledge on the 3-dimensional tissue and vessel architecture is essential. However, the current gold standard in 2-dimensional histology provides only very limited spatial information. Material and methods To elucidate the underlying vascular pathology in Emberger Syndrome on the cellular level, we applied the 3-dimensional visualization and analysis approach VIPAR (volume information-based histopathological analysis by 3D reconstruction and data extraction) to entire wholemount immunofluorescence-stained human tissue samples. VIPAR is a light sheet microscopy-based imaging technique, which allows 3-dimensional reconstruction of entire tissue biopsies followed by automated and semi-automated analysis of vascular parameters in 3-dimensional space. Results Using VIPAR we could show that in Emberger Syndrome the dermal lymphatic vasculature is intact and non-disrupted.However, lower limbs showed an hypoplastic lymphatic vasculature with absence of lymphatic valves in pre-collecting and collecting vessels. In contrast to the lower limbs, the lymphatic vasculature of the upper limbs showed no morphological alterations of lymphatic vessels and lymphatic valves compared to healthy controls. Discussion Based on the 3-dimensional histopathological analysis we were able to perform a detailed phenotyping of lymphatic vessels in the upper and lower limb in Emberger Syndrome and to identify the underlying vascular pathology. In addition, we could show vascular alteration between the upper and lower limbs indicating a vascular heterogeneity of dermal lymph vessels causing the lower limb lymphedema.

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Section: Resultateunclassified

Light sheet microscopy-based 3-dimensional histopathology of the lymphatic vasculature in Emberger syndrome

Hägerling

2020

Phlebologie

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“…Regarding the embryonic development of the lymphovascular system, it is generally accepted that lymph sacs, the first histologically detectable structures of the lymphatic system, are formed by outgrowth of pre-lymphatic clusters from the cardinal veins (Sabin 1909 ; Pollmann et al 2014 ). In recent years, the lymph sacs were proposed to represent the sole origin of the whole lymphatic system of mice (Srinivasan et al 2007 ).…”

Section: Discussionmentioning

confidence: 99%

Integration of CD45-positive leukocytes into newly forming lymphatics of adult mice

Buttler¹,

Lohrberg²,

Groß

et al. 2016

Histochem Cell Biol

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The embryonic origin of lymphatic endothelial cells (LECs) has been a matter of controversy since more than a century. However, recent studies in mice have supported the concept that embryonic lymphangiogenesis is a complex process consisting of growth of lymphatics from specific venous segments as well as the integration of lymphangioblasts into the lymphatic networks. Similarly, the mechanisms of adult lymphangiogenesis are poorly understood and have rarely been studied. We have recently shown that endothelial progenitor cells isolated from the lung of adult mice have the capacity to form both blood vessels and lymphatics when grafted with Matrigel plugs into the skin of syngeneic mice. Here, we followed up on these experiments and studied the behavior of host leukocytes during lymphangiogenesis in the Matrigel plugs. We observed a striking co-localization of CD45+ leukocytes with the developing lymphatics. Numerous CD45+ cells expressed the LEC marker podoplanin and were obviously integrated into the lining of lymphatic capillaries. This indicates that, similar to inflammation-induced lymphangiogenesis in man, circulating CD45+ cells of adult mice are capable of initiating lymphangiogenesis and of adopting a lymphvasculogenic cellular differentiation program. The data are discussed in the context of embryonic and inflammation-induced lymphangiogenesis.Electronic supplementary materialThe online version of this article (doi:10.1007/s00418-015-1399-y) contains supplementary material, which is available to authorized users.

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“…One of the key challenges in investigating the early phases of lymphatic development in the traditional mouse model is áå= îáîç real time imaging to track the movement of individual LECs over development since mouse embryos develop áå= ìíÉêç. Although recent advances allow visualization of developing LECs in mouse embryos, this technique requires specific microscopes and complex preparations (Pollmann= et al, 2014). Therefore, zebrafish can complement the mouse model and offers a unique advantage to unravel cellular behaviors during early lymphatic development.…”

Section: An Old Model With a New Trick?: Zebrafish As An Emerging Modmentioning

confidence: 99%

A Tale of Two Models: Mouse and Zebrafish as Complementary Models for Lymphatic Studies

Kim¹,

Jin²

2014

Molecules and Cells

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Lymphatic vessels provide essential roles in maintaining fluid homeostasis and lipid absorption. Dysfunctions of the lymphatic vessels lead to debilitating pathological conditions, collectively known as lymphedema. In addition, lymphatic vessels are a critical moderator for the onset and progression of diverse human diseases including metastatic cancer and obesity. Despite their clinical importance, there is no currently effective pharmacological therapy to regulate functions of lymphatic vessels. Recent efforts to manipulate the Vascular Endothelial Growth Factor-C (VEGFC) pathway, which is arguably the most important signaling pathway regulating lymphatic endothelial cells, to alleviate lymphedema yielded largely mixed results, necessitating identification of new targetable signaling pathways for therapeutic intervention for lymphedema. Zebrafish, a relatively new model system to investigate lymphatic biology, appears to be an ideal model to identify novel therapeutic targets for lymphatic biology. In this review, we will provide an overview of our current understanding of the lymphatic vessels in vertebrates, and discuss zebrafish as a promising in vivo model to study lymphatic vessels.

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Visualization of Lymphatic Vessel Development, Growth, and Function

Cited by 17 publications

References 69 publications

Light sheet microscopy-based 3-dimensional histopathology of the lymphatic vasculature in Emberger syndrome

Light sheet microscopy-based 3-dimensional histopathology of the lymphatic vasculature in Emberger syndrome

Integration of CD45-positive leukocytes into newly forming lymphatics of adult mice

A Tale of Two Models: Mouse and Zebrafish as Complementary Models for Lymphatic Studies

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