Lymphatic Research Research Articles

Rosalind Franklin Society Proudly Announces the 2023 Award Recipient for Lymphatic Research and Biology.

Rosalind Franklin Society Proudly Announces the 2023 Award Recipient for Lymphatic Research and Biology.

The Role of Exercise in Lymphedema Management: A Bibliometric Analysis

Lymphedema is a lifelong chronic health issue, and exercise approaches are considered one of the gold standards in lymphedema treatment. Numerous articles have been published on exercise approaches in lymphedema. In this study, we aimed to conduct a bibliometric analysis of studies related to exercise in lymphedema. For this purpose, a search was conducted in the Scopus database on October 24, 2023, using the keywords “lymphedema and exercise’’ and 869 documents were examined. Data were downloaded from the relevant search engine. These data were analyzed using the Vosviewer and Biblioshiny package programs. Publication dates ranged from 1957 to 2023. According to the analysis results, while the United States is the leading contributor in terms of article publications (n=979), Austria leads in terms of international collaboration (n=401). The most cited publication using the keywords lymphedema and exercise is the article by Campbell et al. (2019) titled “Exercise Guidelines for Cancer Survivors: Consensus Statement from International Multidisciplinary Roundtable,’’ published in the “Medicine and Science in Sports and Exercise’’ journal with 1101 citations. “Lymphatic Research and Biology”, “Lymphology”, and “Supportive Care in Cancer” are the top three journals with the most citations in this field. Particularly, the University of Pennsylvania stands out as the most prolific institution contributing to this area with productive research output. The most prolific author with 29 articles is Kathryn H. Schmitz. The most frequently used keywords include “lymphedema”, “breast cancer”, and “lymphedema, quality of life”. The findings of this study are valuable not only for researchers and practitioners interested in lymphedema and exercise but also for anyone interested in practical applications and potential future developments. Ultimately, this comprehensive information guide could serve as an important resource and roadmap for future studies.

A scoping review of lymphatic filariasis research in Zambia

A scoping review of lymphatic filariasis research in Zambia

Genetic targeting of lymphatic endothelial cells in mice: current strategies and future perspectives.

Lymphatic vessels within different organs have diverse developmental origins, depend on different growth factor signaling pathways for their development and maintenance, and display notable tissue-specific adaptations that contribute to their roles in normal physiology and in various diseases. Functional studies on the lymphatic vasculature rely extensively on the use of mouse models that allow selective gene targeting of lymphatic endothelial cells (LECs). Here, we discuss LEC diversity and provide an overview of some of the commonly used LEC-specific inducible Cre lines and induction protocols, outlining essential experimental parameters and their implications. We describe optimized treatment regimens for embryonic, postnatal and adult LECs, efficiently targeting organs that are commonly studied in lymphatic vascular research, such as the mesentery and skin. We further highlight the anticipated outcomes and limitations associated with each induction scheme and mouse line. The proposed protocols serve as recommendations for laboratories initiating studies involving targeting of the lymphatic vasculature, and aim to promote uniformity in lineage tracing and functional studies within the lymphatic vascular field.

Automated Cut&run Brings Scalable Epigenomic Profiling to Hematology

Genome-wide association studies (GWAS) and corresponding transcriptomics research have been leveraged to identify disease risk variants in hematological disorders with the hopes of developing more personalized treatment regimens. Interestingly, >90% of GWAS-identified variants are found in non-coding regions of the genome, indicating they likely affect the regulatory machinery that governs chromatin structure. Non-coding elements, such as enhancers, play important roles in supporting chromatin mechanisms, including cell-type specific gene expression, cell fates and disease states. However, these variants are difficult to study compared to protein-coding mutations and have been challenging to directly associate with phenotypic readouts. To date, efforts to understand the effects of non-coding variants on chromatin dynamics have been focused on chromatin accessibility (ATAC-seq) and DNA methylation profiling. Notably, these assays can only provide a binary, “open-or-closed,” view of chromatin and often fail to provide mechanistic insight into disease etiology. Epigenomic features - such as histone post-translational modifications (PTMs) and chromatin-associated proteins - mark distinct genomic compartments (e.g., promoters, enhancers) and regulate chromatin structure, gene expression, and cell function. Mapping these features provides a rich context to study cell fate and has great potential for discovering new biomarkers and drug targets. Despite this, efforts to integrate epigenomics into large scale lymphatic and myeloid research have been hampered by the poor sensitivity, high background, and low throughput of traditional chromatin mapping technology (i.e., ChIP-seq). Here, we present autoCUT&RUN, a high throughput assay for rapid, ultra-sensitive profiling of epigenomic features from FACS-isolated primary cells or tissues. This workflow generates reliable profiles from <10,000 cells per reaction, and is supported by a rigorous optimization strategy, high-quality antibodies, and quantitative spike-in controls. As part of a multi-site collaboration with the Immunological Genome Consortium, we used our autoCUT&RUN platform to build a comprehensive epigenomic database of mouse immune cells - composed of >1,500 epigenomic profiles from >100 different FACS-isolated primary immune cell types. These studies set the stage to leverage high-throughput epigenomics for multi-site clinical studies to identify and/or characterize novel biomarkers for precision medicine applications. Further, we will discuss our integration of CUT&RUN and Enzymatic Methylation-sequencing (CUT&RUN-EM) to deliver a true multiomic view of the co-occurrence of epigenomic features and DNA methylation, which can reveal multivalent cellular mechanisms and deconvolute sample heterogeneity.

Investigation of optimizing indocyanine green solution for in vivo lymphatic research using near-infrared fluorescence indocyanine green lymphangiography

Despite the tireless efforts of many researchers in lymphatic research, indocyanine green (ICG) solution conditions suitable for lymphatic circulation tests have not been perfectly established yet. We aimed to investigate the optimal in vivo conditions of ICG solution to avoid photobleaching and quenching effects, which may affect the accuracy of lymphatic circulation evaluation. After ICG fluorescence intensity (or ICG intensity) was assessed under different in vitro conditions, the image quality of brachial lymph nodes (LNs) and collecting lymphatic vessels (LVs) in eight rats was investigated. The in vitro results showed that ICG intensity depends on concentration and time in various solvents; however, the brightest intensity was observed at a concentration of 8–30 μg/mL in all solvents. ICG concentration in the albumin (bovine serum albumin; BSA) solution and rat’s plasma showed more than two times higher fluorescence intensity than in distilled water (DW) in the same range. However, saline reduced the intensity by almost half compared to DW. In the in vivo experiment, we obtained relatively high-quality images of the LNs and LVs using ICG in the BSA solution. Even at low concentrations, the result in the BSA solution was comparable to those obtained from high-concentration solutions commonly used in conventional circulation tests. This study provides valuable information about the conditions for optimal ICG intensity in near infrared fluorescence indocyanine green (NIRF-ICG) lymphangiography, which may be useful not only for the diagnosis of lymphatic circulation diseases such as lymphedema but also for preclinical research for the lymphatic system.

Rosalind Franklin Society Proudly Announces the 2022 Award Recipient for Lymphatic Research and Biology.

Rosalind Franklin Society Proudly Announces the 2022 Award Recipient for Lymphatic Research and Biology.

Murine Dermal Lymphatic Endothelial Cell Isolation.

The lymphatic system participates in the regulation of immune surveillance, lipid absorption, and tissue fluid balance. The isolation of murine lymphatic endothelial cells is an important process for lymphatic research, as it allows the performance of in vitro and biochemical experiments on the isolated cells. Moreover, the development of Cre-lox technology has enabled the tissue-specific deficiency of genes that cannot be globally targeted, leading to the precise determination of their role in the studied tissues. The dissection of the role of certain genes in lymphatic physiology and pathophysiology requires the use of lymphatic-specific promoters, and thus, the experimental verification of the expression levels of the targeted genes. Methods for efficient isolation of lymphatic endothelial cells from wild-type or transgenic mice enable the use of ex vivo and in vitro assays to study the mechanisms regulating the lymphatic functions and the identification of the expression levels of the studied proteins. We have developed, standardized and present a protocol for the efficient isolation of murine dermal lymphatic endothelial cells (DLECs) via magnetic bead purification based on LYVE-1 expression. The protocol outlined aims to equip researchers with a tool to further understand and elucidate important players of lymphatic endothelial cell functions, especially in facilities where fluorescence-activated cell sorting equipment is not available.

Update April 2023

Lymphatic Research and BiologyVol. 21, No. 2 Literature WatchUpdate April 2023Francine BleiFrancine BleiHassenfeld Children's Hospital at NYU Langone, The Laurence D. And Lori Weider Fink Children's Ambulatory Care Center, New York, New York, USA.Search for more papers by this authorPublished Online:20 Apr 2023https://doi.org/10.1089/lrb.2023.29139.fbAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 21Issue 2Apr 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Francine Blei.Update April 2023.Lymphatic Research and Biology.Apr 2023.194-226.http://doi.org/10.1089/lrb.2023.29139.fbPublished in Volume: 21 Issue 2: April 20, 2023PDF download

Breast Cancer-Related Lymphedema: The Primary/Secondary Conundrum

Lymphatic Research and BiologyVol. 21, No. 2 EditorialFree AccessBreast Cancer-Related Lymphedema: The Primary/Secondary ConundrumStanley G. RocksonStanley G. RocksonEditor-in-Chief, Stanford University School of Medicine, Stanford, California, USA.Search for more papers by this authorPublished Online:20 Apr 2023https://doi.org/10.1089/lrb.2023.29141.editorialAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail For quite some time, within the pages of this journal1–3 and elsewhere,4,5 there has been a persistent theory that there might be systemic and other predispositions to the secondary (or acquired) lymphedema that is encountered frequently as a sequela of breast cancer therapeutics. In addition, it has recently been observed that the presence of a lymphatic disorder such as breast cancer-associated lymphedema can alter the patterns of associated systemic disease expression that exist as comorbidities.6 These phenomena help to blur the distinction between “primary” and “secondary” lymphedema.In the current issue of Lymphatic Research and Biology, we provide three additional sets of original observations that help to expand insights into this hypothesis.In the first of these, Kim and colleagues have explored rates of incidental subclinical lymphedema in the contralateral arm of patients with unilateral postsurgical secondary upper extremity lymphedema. In their study, magnetic resonance imaging of the upper extremities was utilized to examine patients with unilateral upper extremity clinical lymphedema. Axial STIR MR images of the symptomatic and contralateral arms were retrospectively reviewed and edema severity was graded by the investigators. In these 78 examined subjects, contralateral abnormalities were detected in 14.1%. Although the direct conclusion was to emphasize the importance of evaluation of the contralateral limb, the interpretation, by extension, is that there is a disturbance in lymphatic anatomy or function that extends beyond the direct lymphatic trauma of cancer therapeutics.The second investigation, by Furlan and colleagues, examines the phenomenon of blood flow abnormalities in the limb that precede the development of overt lymphedema. In a cohort of 200 subjects, Doppler ultrasound was utilized to examine the axillary and brachial arteries. In these patients, there was detection of higher mean flow velocity and end-diastolic velocity as early as 1 month after surgery. The end-diastolic velocity demonstrated a 73.7% sensitivity and 71.2% specificity as a predictor of long-term lymphedema, with a negative predictive value of 57.6%.The third of these three new investigations proposed a pilot investigation of abdominal fat ratio in subjects with breast cancer-related lymphedema. Here, Nakipoğlu and colleagues investigated the impact of central obesity to the occurrence of this lymphedema presentation. They investigated cohorts of postsurgical subjects with a matched control cohort that differed only in the distribution of BMI. The abdominal circumference measurement demonstrated a modest predictive utility, with a predictive specificity of 89%.In aggregate, these three newly published investigations continue to tantalize us with the increasingly tenable hypothesis that the appearance of acquired lymphedema (in this case following breast cancer therapies) may, and likely does, depend upon systemic factors that predict the likelihood of disease evolution. Continued exploration of these phenomena will, ideally, result in enhanced risk factor stratification, diagnostic evaluation, and, with good fortune, improved risk factor reduction strategies.

Mapping the lymphatic system across body scales and expertise domains: A report from the 2021 National Heart, Lung, and Blood Institute workshop at the Boston Lymphatic Symposium.

Enhancing our understanding of lymphatic anatomy from the microscopic to the anatomical scale is essential to discern how the structure and function of the lymphatic system interacts with different tissues and organs within the body and contributes to health and disease. The knowledge of molecular aspects of the lymphatic network is fundamental to understand the mechanisms of disease progression and prevention. Recent advances in mapping components of the lymphatic system using state of the art single cell technologies, the identification of novel biomarkers, new clinical imaging efforts, and computational tools which attempt to identify connections between these diverse technologies hold the potential to catalyze new strategies to address lymphatic diseases such as lymphedema and lipedema. This manuscript summarizes current knowledge of the lymphatic system and identifies prevailing challenges and opportunities to advance the field of lymphatic research as discussed by the experts in the workshop.

Update February 2023

Lymphatic Research and BiologyVol. 21, No. 1 Literature WatchUpdate February 2023Francine BleiFrancine BleiHassenfeld Children's Hospital at NYU Langone, NYU Grossman School of Medicine, New York, New York, USA.Search for more papers by this authorPublished Online:16 Feb 2023https://doi.org/10.1089/lrb.2023.29136.fbAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 21Issue 1Feb 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Francine Blei.Update February 2023.Lymphatic Research and Biology.Feb 2023.78-96.http://doi.org/10.1089/lrb.2023.29136.fbPublished in Volume: 21 Issue 1: February 16, 2023PDF download

History of the development of the lymphatic system (part one)

The history of lymphatic system research goes back to ancient times. Lymph nodes were likely first mentioned in the hieroglyphs of ancient Egypt. Hippocrates (5th century BC) in the 5th century BC was one of the first to mention the lymphatic system. One of the first descriptions of what can be attributed to lymphatic vessels can be found in Aristotle. The Byzantine physician Pavlo Aeginsky was a famous surgeon who illustrated the tonsils and performed the first tonsillectomy, which allowed him to identify and describe infected cervical lymph nodes. Indian and Islamic medicine, especially Avicenna, gave interesting descriptions of lymphedema (elephant disease) due to frequent parasitic infections which are more common in eastern regions. Rufus of Ephesus, a Roman physician, discovered the axillary, inguinal, and mesenteric lymph nodes, as well as the thymus, in the 1st-2nd century AD. The first mention of lymphatic vessels was in the 3rd century BC by Herophilus, a Greek anatomist who lived in Alexandria. The Alexandrian school made significant contributions to the study of the lymphatic system stemming from the works of Galen. However, whether the structures described were lymphatic vessels is still debated. Erasistratus, during the dissection of a dairy lamb, showed that the abdominal arteries are filled with milk. Very likely, this is the first misinterpreted study of mesenteric lymphatic vessels. Based on the first observations made by the medieval Arab anatomist ibn Al-Nafis, the Spanish scientist and theologian Miguel Servetus, and the Italian anatomist Realdo Colombo, who described pulmonary circulation, and Andrea Cesalpino, who first introduced the term "circulation" in relation to the cardiovascular system, it was established basic regularities of the structure of the lymphatic system. In the middle of the 16th century, Gabriele Fallopio (researcher of fallopian tubes) described the vessels now known as "mammary glands". Based on all these discoveries, the Italian surgeon and anatomist Giovanni Guglielmo Riva was the first to present a graphic representation of the lymphatic system in two of his four oil paintings, which are now kept in the Academy of History "Arte Sanitaria" in Rome.

Visual analysis of global research output of lymphedema based on bibliometrics.

BackgroundGlobally, several generations of doctors in the field of lymphedema have created numerous publications. To date, no bibliometric analysis has been performed specifically on these publications. For the further promotion of research on lymphedema and to align with the international research frontiers, it is essential to understand the current state of Lymphedema research output.ObjectiveThis study aims to statistically and visually analyze the characteristics of publications output, distribution of contributions and development process of lymphedema, enriching the knowledge base of Lymphedema, and then seek potential research topics and collaborators.MethodsBased on the Web of Science core collection database, we firstly analyzed the quantity and quality of publications in the field of lymphedema, secondly profiled the publishing groups in terms of country, institution, author’s publication and cooperation network, and finally sorted out and summarized the hot topics of research.ResultsA total of 8569 papers were retrieved from 1900-2021. The top4 journals with the most publications were LYMPHOLOGY, LYMPHATIC RESEARCH AND BIOLOGY, PLASTIC AND RECONSTRUCTIVE SURGERY and ANNALS OF SURGICAL ONCOLOGY. The top 4 countries with the most publications were USA, Japan, UK, and China. The United States dominates the total number of publications and the international cooperation network. The most productive research institution is Harvard University, and the research institution with the most collaborating institutions is Memorial Sloan Kettering Cancer Center. Mortimer, Peter S contributes the most research in this field. The research achievements of Japanese scholars in this field are of great significance. The top 5 ranked keywords are “Breast Cancer”, “Health-Related Quality Of Life”, “Lymphscintigraphy”, “Lymphovenous Anastomosis”, and “Lymphangiogenesis”.ConclusionMore and more scholars are devoted to the research of cancer-related Lymphedema. It is foreseeable that breast cancer-related lymphedema and lymphangiogenesis will remain a focus of future research. Advances in Lymphatic vessel imaging and the development of lymphatic microsurgery will further play a role in the clinical workup of lymphedema. Meanwhile, This study can help researchers identify potential collaborators and partner institutions and contribute to further research.

Research Matters

Lymphatic Research and BiologyVol. 20, No. 3 Research MattersFree AccessResearch MattersPublished Online:10 Jun 2022https://doi.org/10.1089/lrb.2022.29123.wrAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail National Institutes of Health Begins Planning for National Commission on Lymphatic ResearchOn March 9, the FY2022 Omnibus bill directed the National Institutes of Health (NIH) to establish a National Commission on Lymphatic Diseases and further called for the creation of an NIH research category specifically for lymphedema (LE). Without a category to date, the secondary status of LE was being perpetuated. It also meant NIH was unable to report on levels of LE research when queried by Congress.Then, on March 18, a representative of the National Heart, Lung, and Blood Institute wrote on behalf of its Director Dr. Gary Gibbons in response to an open letter written by Lymphatic Education and Research Network (LE&RN) President and CEO William Repicci. The planning is now beginning for the National Commission, and NIH is already engaged in creating research categories for both LE and lymphatic diseases.President's FY 2023 Budget Request to Congress ReleasedPresident Biden's budget seeks increases to NIH as well as proposing $5 billion for the new Advanced Research Project Agency for Health (ARPA-H) within NIH. ARPA-H is so important to lymphatic research because it represents a substantial budget that is not currently committed to any project. The goal of ARPA-H is to create breakthroughs and build platforms to revolutionize prevention, treatment, and cures of diseases. Its mission is to overcome market failures. Lymphatic research, such as LE research, fits squarely in ARPA-H's mission.Centers of Excellence Lymphatic Summit 2021 Now Open AccessLE&RN's 2021 Virtual Summit: The Continuum From Evolving Research to State-of-the-Art Lymphatic Management is now available for open-access viewing. The rapidly evolving world of lymphatic research is already creating a substantial impact upon the practice of lymphatic medicine. The 2021 State-of-the-Art Lymphatic Medicine Summit highlights the interface between the investigative process and the optimal current management of lymphatic patients. Evolving concepts and unanswered questions are emphasized.For instant access: https://learn.regfox.com/wld-2021-virtual-lymphatic-summit-admissionLet's Talk Lymphedema Is Now Open AccessOn World Lymphedema Day 2021, LE&RN broadcast Let's Talk Lymphedema, the first-ever play written and produced about living with LE. That play is now available to all. Watch it on LE&RN's website at www.lymphaticnetwork.org/lets-talk-le.LE&RN Symposium SeriesOn June 1, Roman Skoracki, MD presented Head and Neck Lymphedema for LE&RN supporters on Zoom. In May, Max Itkin, MD presented “Beyond Lymphedema: New Developments in Central Lymphatic Imaging and Interventions.” In April, Sheila H. Ridner, PhD, RN, FAAN presented Secondary Lymphedema Prevention: A Randomized Clinical Trial Evaluating Early Detection and Intervention in Breast Cancer Patients. All LE&RN Symposiums are available as replays on LE&RN's website at https://lymphaticnetwork.org/symposium-series.LE&RN Creates Lymphatic Researcher Database for NIHAt NIH's request, LE&RN has created a Lymphatic Researcher Database (https://lymphaticnetwork.org/treating-lymphedema/researchers) to keep NIH informed of the lymphatic research being pursued worldwide. LE&RN now needs all lymphatic researchers to submit information for this webpage by contacting LE&RN at LERN@LymphaticNetwork.org. Research names, institutions, PubMed weblinks, and brief research descriptions will appear on this page, searchable by name, institution, or topic. Researchers, if you have already provided information here but need to update it, you may do so by contacting LE&RN at LERN@LymphaticNetwork.org. All 27 NIH Institutes and Centers have been provided this weblink. This initiative grew out of the efforts of the Trans-NIH Lymphatics Coordinating Committee.Annual Global Virtual LymphWalkLE&RN's annual LymphWalk took place globally, virtually, and in person at Artesani Park in Boston on May 15, 2022. After the global event, participants around the world tuned in for a virtual program on Monday, May 16. There LE&RN shared recent treatment breakthroughs, honored doctors and patients fighting lymphatic diseases, and gave a glimpse of exciting new medical advances on the horizon.William RepicciPresident and CEOLymphatic Education and Research Network (LE&RN)www.lymphaticnetwork.orgFiguresReferencesRelatedDetails Volume 20Issue 3Jun 2022 InformationCopyright 2022, Mary Ann Liebert, Inc., publishersTo cite this article:Research Matters.Lymphatic Research and Biology.Jun 2022.352-352.http://doi.org/10.1089/lrb.2022.29123.wrPublished in Volume: 20 Issue 3: June 10, 2022PDF download

Lymphatic Interventions in the Cancer Patient.

The incidence of lymphatic leakage (iatrogenic and non-iatrogenic) is growing in cancer population due to the increased complexity of the surgical procedures and improved overall survival in cancer patients. The purpose of this article is to review the contemporary approach in the field of percutaneous lymphatic embolization in cancer patients with lymphatic leaks. Since the advent of intranodal lymphangiography in 2011 alongside with the MR and CT lymphangiography, the accuracy of diagnosis of the lymphatic diseases has significantly improved significantly. These advancements have triggered a revival of minimally invasive lymphatic interventions. Lymphatic embolization is expanding from the classic indication, thoracic duct embolization, to other lymphatic disorders (chylous ascites, lymphoceles, liver lymphorrhea, protein-losing enteropathy). The growth of lymphatic research and the standardization of the lymphatic interventions require a multidisciplinary and collaborative approach between physicians and researchers.

Hypoxia and Hypoxia-Inducible Factors in Lymphedema.

Lymphedema is a chronic inflammatory disorder characterized by edema, fat deposition, and fibrotic tissue remodeling. Despite significant advances in lymphatic biology research, our knowledge of lymphedema pathology is incomplete. Currently, there is no approved pharmacological therapy for this debilitating disease. Hypoxia is a recognized feature of inflammation, obesity, and fibrosis. Understanding hypoxia-regulated pathways in lymphedema may provide new insights into the pathobiology of this chronic disorder and help develop new medicinal treatments.

Lymphatic Collecting Vessel: New Perspectives on Mechanisms of Contractile Regulation and Potential Lymphatic Contractile Pathways to Target in Obesity and Metabolic Diseases.

Obesity and metabolic syndrome pose a significant risk for developing cardiovascular disease and remain a critical healthcare challenge. Given the lymphatic system’s role as a nexus for lipid absorption, immune cell trafficking, interstitial fluid and macromolecule homeostasis maintenance, the impact of obesity and metabolic disease on lymphatic function is a burgeoning field in lymphatic research. Work over the past decade has progressed from the association of an obese phenotype with Prox1 haploinsufficiency and the identification of obesity as a risk factor for lymphedema to consistent findings of lymphatic collecting vessel dysfunction across multiple metabolic disease models and organisms and characterization of obesity-induced lymphedema in the morbidly obese. Critically, recent findings have suggested that restoration of lymphatic function can also ameliorate obesity and insulin resistance, positing lymphatic targeted therapies as relevant pharmacological interventions. There remain, however, significant gaps in our understanding of lymphatic collecting vessel function, particularly the mechanisms that regulate the spontaneous contractile activity required for active lymph propulsion and lymph return in humans. In this article, we will review the current findings on lymphatic architecture and collecting vessel function, including recent advances in the ionic basis of lymphatic muscle contractile activity. We will then discuss lymphatic dysfunction observed with metabolic disruption and potential pathways to target with pharmacological approaches to improve lymphatic collecting vessel function.

Research Output on Lymphatic Filariasis Research: A Scientometric Analysis During 2009 to 2018

Research Output on Lymphatic Filariasis Research: A Scientometric Analysis During 2009 to 2018

Quantitative 3-dimensional imaging and tissue cytometry reveals lymphatic expansion in acute kidney injury

The lymphatic system plays an integral role in physiology and has recently been identified as a key player in disease progression. Tissue injury stimulates lymphatic expansion, or lymphangiogenesis (LA), though its precise role in disease processes remains unclear. LA is associated with inflammation, which is a key component of acute kidney injury (AKI), for which there are no approved therapies. While LA research has gained traction in the last decade, there exists a significant lack of understanding of this process in the kidney. Though innovative studies have elucidated markers and models with which to study LA, the field is still evolving with ways to visualize lymphatics in vivo. Prospero-related homeobox-1 (Prox-1) is the master regulator of LA and determines lymphatic cell fate through its action on vascular endothelial growth factor receptor expression. Here, we investigate the consequences of AKI on the abundance and distribution of lymphatic endothelial cells using Prox1-tdTomato reporter mice (ProxTom) coupled with large-scale three-dimensional quantitative imaging and tissue cytometry (3DTC). Using these technologies, we describe the spatial dynamics of lymphatic vasculature in quiescence and post-AKI. We also describe the use of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) as a marker of lymphatic vessels using 3DTC in the absence of the ProxTom reporter mice as an alternative approach. The use of 3DTC for lymphatic research presents a new avenue with which to study the origin and distribution of renal lymphatic vessels. These findings will enhance our understanding of renal lymphatic function during injury and could inform the development of novel therapeutics for intervention in AKI.Lymphangiogenesis (LA) is a process that occurs as a response to tissue injury, though the precise role of de novo lymphatic vessel development remains unclear. Here, authors describe quantitative three-dimensional imaging and tissue cytometry, a novel technique with which to study the distribution and spatial dynamics of LA in the context of acute kidney injury.