Lymphatic‐to‐blood vessel transition in adult microvascular networks: A discovery made possible by a top‐down approach to biomimetic model development

Objective Emerging areas of vascular biology focus on lymphatic/blood vessel mispatterning and the regulation of endothelial cell identity. However, a fundamental question remains unanswered: Can lymphatic vessels become blood vessels in adult tissues? Leveraging a novel tissue culture model, the ob...

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Published in:Microcirculation (New York, N.Y. 1994) N.Y. 1994), 2020-02, Vol.27 (2), p.e12595-n/a
Main Authors: Azimi, Mohammad S., Motherwell, Jessica M., Hodges, Nicholas A., Rittenhouse, Garret R., Majbour, Dima, Porvasnik, Stacey L., Schmidt, Christine E., Murfee, Walter L.
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Biomimetics
Blood vessels
Capillaries - diagnostic imaging
Capillaries - metabolism
endothelial cell
Endothelial Cells - cytology
Endothelial Cells - metabolism
lymphangiogenesis
lymphatic
Lymphatic system
Lymphatic Vessels - diagnostic imaging
Lymphatic Vessels - metabolism
Male
microcirculation
Models, Cardiovascular
Rats
Rats, Wistar
Vascular Remodeling
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Summary:Objective Emerging areas of vascular biology focus on lymphatic/blood vessel mispatterning and the regulation of endothelial cell identity. However, a fundamental question remains unanswered: Can lymphatic vessels become blood vessels in adult tissues? Leveraging a novel tissue culture model, the objective of this study was to track lymphatic endothelial cell fate over the time course of adult microvascular network remodeling. Methods Cultured adult Wistar rat mesenteric tissues were labeled with BSI‐lectin and time‐lapse images were captured over five days of serum‐stimulated remodeling. Additionally, rat mesenteric tissues on day 0 and day 3 and 5 post‐culture were labeled for PECAM + LYVE‐1 or PECAM + podoplanin. Results Cultured networks were characterized by increases in blood capillary sprouting, lymphatic sprouting, and the number of lymphatic/blood vessel connections. Comparison of images from the same network regions identified incorporation of lymphatic vessels into blood vessels. Mosaic lymphatic/blood vessels contained lymphatic marker positive and negative endothelial cells. Conclusions Our results reveal the ability for lymphatic vessels to transition into blood vessels in adult microvascular networks and discover a new paradigm for investigating lymphatic/blood endothelial cell dynamics during microvascular remodeling.
ISSN:1073-9688
1549-8719
DOI:10.1111/micc.12595