Homeostatic maintenance of the lymphatic vasculature

Stritt, Simon; Koltowska, Katarzyna; Mäkinen, Taija

doi:10.1016/j.molmed.2021.07.003

Cited by 53 publications

(34 citation statements)

References 173 publications

(236 reference statements)

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“…Extending these findings to LVs, it is certain that these vessels similarly experience pro-survival signaling, the disruption of which can lead to LV regression ( Figure 3 ). Although the LV network experiences less shear stress than the BV network, Stritt et al (2021) showed that LVs have greater sensitivity to shear stress and further elucidated the mechanisms by which shear stress may lead to LEC proliferation in vitro . In addition to LEC proliferation and potential survival, shear stress has also been implicated in the survival of lymphatic valves ( Iyer et al, 2020 ).…”

Section: Learning From Blood Vessel Regressionmentioning

confidence: 97%

“… Regulation of LV quiescence and growth in adults, reproduced from Stritt et al (2021) . Mechanisms that regulate the maintenance of LEC quiescence (upper left box) and the reactivation of LV growth and regeneration in adult tissues are depicted.…”

Section: Learning From Blood Vessel Regressionmentioning

confidence: 99%

“…In contrast to BVs’ dependence on autocrine VEGF-A, most LVs do not seem to require continuous VEGF-C signaling for homeostasis; intestinal and meningeal lymphatics are cited as exceptions ( Stritt et al, 2021 ). Thus, it is likely that there are more nuances left to be unearthed in lymphatic vessel maintenance signaling.…”

Section: Learning From Blood Vessel Regressionmentioning

confidence: 99%

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Lymphatic Vessel Regression and Its Therapeutic Applications: Learning From Principles of Blood Vessel Regression

et al. 2022

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Aberrant lymphatic system function has been increasingly implicated in pathologies such as lymphedema, organ transplant rejection, cardiovascular disease, obesity, and neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. While some pathologies are exacerbated by lymphatic vessel regression and dysfunction, induced lymphatic regression could be therapeutically beneficial in others. Despite its importance, our understanding of lymphatic vessel regression is far behind that of blood vessel regression. Herein, we review the current understanding of blood vessel regression to identify several hallmarks of this phenomenon that can be extended to further our understanding of lymphatic vessel regression. We also summarize current research on lymphatic vessel regression and an array of research tools and models that can be utilized to advance this field. Additionally, we discuss the roles of lymphatic vessel regression and dysfunction in select pathologies, highlighting how an improved understanding of lymphatic vessel regression may yield therapeutic insights for these disease states.

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Section: Learning From Blood Vessel Regressionmentioning

confidence: 97%

Section: Learning From Blood Vessel Regressionmentioning

confidence: 99%

Section: Learning From Blood Vessel Regressionmentioning

confidence: 99%

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Lymphatic Vessel Regression and Its Therapeutic Applications: Learning From Principles of Blood Vessel Regression

et al. 2022

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“…The accumulation of lymph in the interstitial tissue leads to remodeling of the skin and subcutaneous tissue and the accumulation of fibroadipose tissue [ 7 ]. The chronic form of lymphedema is characterized by swelling, fibrosis, accumulation of adipose tissue and infiltration of immune cells.…”

Section: Introductionmentioning

confidence: 99%

Cell therapy as a treatment of secondary lymphedema: a systematic review and meta-analysis

et al. 2021

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Background Lymphedema, the accumulation of interstitial fluid caused by poor lymphatic drainage, is a progressive and permanent disease with no curative treatment. Several studies have evaluated cell-based therapies in secondary lymphedema, but no meta-analysis has been performed to assess their efficacy. Methods We conducted a systematic review and meta-analysis of all available preclinical and clinical studies, with assessment of their quality and risk of bias. Results A total of 20 articles using diverse cell types were selected for analysis, including six clinical trials and 14 pre-clinical studies in three species. The meta-analysis showed a positive effect of cell-based therapies on relevant disease outcomes (quantification of edema, density of lymphatic capillaries, evaluation of the lymphatic flow, and tissue fibrosis). No significant publication bias was observed. Conclusion Cell-based therapies have the potential to improve secondary lymphedema. The underlying mechanisms remain unclear. Due to relevant heterogeneity between studies, further randomized controlled and blinded studies are required to substantiate the use of these novel therapies in clinical practice.

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“…The signals, including cells, antigens, and cytokines, that lymphatic vessels do or do not transmit thus play critical roles in shaping immunity and autoimmunity. Lymphatic vessels begin as blind-ended capillaries in tissue, which reabsorb interstitial fluid and molecules (see [1,2] for recent reviews on lymphatic ontogeny, function and signalling). Vessels are dynamic and can change their permeability and undergo lymphangiogenesis under different stimuli.…”

Section: Introductionmentioning

confidence: 99%

Advances in understanding and examining lymphatic function: relevance for understanding autoimmunity

Ambler

Santambrogio

2021

Current Opinion in Rheumatology

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Purpose of reviewThe aim of this review is to give insights into how novel lymphatics functions may influence autoimmunity. Recent findingsThe lymphatic system connects peripheral tissues to draining lymph nodes to regulate adaptive immunity and directly interfaces with leukocytes in lymph vessels and in the lymph node. Here, we discuss recent findings showing evidence of dysfunctional lymphatics in autoimmune disease, new understanding of how afferent lymphatic regulation can modulate immunity, lymph node lymphatic heterogeneity and how these lymphatics can directly modulate lymphocyte function, how this understanding can be harnessed for new therapeutics, and new tools for the investigation of lymphatic and immune biology. SummaryLymphatics have an active role in the regulation of inflammation and the adaptive immune response. Here, we review recent findings in lymphatics biology in peripheral tissues and lymph nodes and emphasize the relevance for better understanding autoimmune diseases.

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Homeostatic maintenance of the lymphatic vasculature

Abstract: The lymphatic vasculature is an active multifaceted regulator of tissue homeostasis, growth, and regeneration.

Cited by 53 publications

References 173 publications

Lymphatic Vessel Regression and Its Therapeutic Applications: Learning From Principles of Blood Vessel Regression

Lymphatic Vessel Regression and Its Therapeutic Applications: Learning From Principles of Blood Vessel Regression

Cell therapy as a treatment of secondary lymphedema: a systematic review and meta-analysis

Advances in understanding and examining lymphatic function: relevance for understanding autoimmunity

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