Project: 3D-Histopathology of Lipedema

Principal Investigator: René Hägerling, MD, PhD
Charité - Universitätsmedizin Berlin
Institute of Medical and Human Genetics
Berlin, Germany

Summary

This research project aims to unravel the underlying histological alterations in Lipedema to improve our understanding of the disease and to develop a diagnostic test based on the 3D-histology of tissue samples.

Background

In a previous study, we applied optical sectioning on tissue biopsies from Lipedema patients and healthy controls to investigate histological alterations associated with Lipedema. Using this approach, we were able to perform digital 3-dimensional reconstruction of entire tissue biopsies and analyze the 3-dimensional blood and lymphatic vascular network as well as adipocytes of the entire biopsy in an automated and unbiased manner. The 3-dimensional reconstruction allowed visual interpretation and comparison of the respective structures of interest between Lipedema and control samples.

In a pilot project, we have analyzed two small cohorts using this approach. Our preliminary data showed no major alterations in blood and lymphatic vessels in Lipedema compared to controls, however, fat cells from Lipedema patients showed characteristic alterations in terms of fat cell number, volume, and diameter.

In this project, we aim to validate these results in larger cohorts and aim to investigate if these alterations are specific for Lipedema.

Methodology

Research contents/study design: This is an observational study of histological tissue architecture in Lipedema patients. The aim of the study is to identify histological changes in the skin and adipose tissue in Lipedema. For this purpose, tissue samples are collected and stained for relevant markers. Following a 3-dimensional histological visualization, data will be analyzed. This will reveal characteristic changes that are specific to Lipedema.

Cohort/Intervention: Tissue biopsies are collected from Lipedema patients, BMI-matched controls as well as obese patients.

Measures: In this project, we will focus on blood and lymphatic vessels as well as fat cells. Therefore, we will visualize these structures and cells and will compare them between Lipedema, healthy controls, and tissue samples from obese patients. For the comparison we will calculate various vessel parameters, e.g. vessel branching and volume, as well as parameters describing the morphology of fat cells, e.g. fat cell volume and diameter. This will allow us to identify Lipedema-specific alterations which can be used for histological diagnosis in the future.

Expected outcomes

We hypothesis that adipocytes in Lipedema have a Lipedema-specific morphology that is not only distinct from healthy tissues but also from obesity and lymphedema. These alterations can be used in the future to develop a histological test distinguishing between these conditions.

Practical implementations of results

Our work will set the basis for the identification of Lipedema-specific histological characteristics. Based on a significant cohort of patients, relevant data on the histology of Lipedema will be obtained. This data can be used in the future to develop a diagnostic test for Lipedema, which allows unbiased distinction between Lipedema and phenotypically similar conditions.

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