Project: Investigating the diagnostic and therapeutic potential of CD163 biomarker in lipedema

Principal Investigator: Epameinondas Gousopoulos, MD, PhD
Department of Plastic Surgery and Hand Surgery
University Hospital Zurich
Zurich, Switzerland

Summary

This project builds on previously published findings of our group, suggesting a critical role of distinct immunosuppressive macrophage populations in lipedema. Therefore, we now investigate in depth the diagnostic, monitoring and therapeutic implications of this distinct macrophage population as a biomarker and pharmaceutical target.

Background

Beside the fibroadipose tissue overgrowth, lipedema is characterized by a distinct immune cell composition, with abundant levels of immunosuppressive (M2-polarized) macrophages residing in the subcutaneous adipose tissue of lipedema patients. This distinct immunological niche distinguishes phenotypically lipedema from obesity, lipohypertrophy or lymphedema, presenting a possible biomarker function. Additionally, lipedema-derived macrophage transcriptomics, followed by in vitro functional assays highlight their potential role as a therapeutic pharmaceutical target, to influence lipedema adipose tissue differentiation and metabolism.

Methodology

In this study, we use lipedema tissue biopsies (subcutaneous fat and liquid biopsies) obtained from patients across all stages of the condition in comparison to biopsies from gender-, BMI- and anatomic location- matched healthy controls to examine and verify a potential biomarker target, to diagnose the presence of lipedema. Additionally, the comparison of the same molecules across different stages will be used to assess a potential usage as a monitoring tool of lipedema progression. 

The therapeutic implication of the same molecule as a drug target will be assessed in functional in vitro and ex vivo experiments, treating tissues or cells extracted from lipedema and control patients. Pharmaceutical candidates will be assessed for their potential to modify adipose tissue differentiation and metabolism. Phenotypic and functional characterization will be performed, including transcriptomic analysis, in an effort to underpin the molecular pathways involved.

Expected outcomes

The results of the current work will be able to indicate with confidence, whether distinct immunosuppressive macrophages populations do qualify as a lipedema biomarker, to diagnose and/or monitor the disease. Additionally, the functional in vitro and ex vivo studies will indicate the therapeutic potential of selected drug candidates against our validated target and the potential to influence lipedema adipose tissue growth and metabolism.

Practical implementations of results

The study builds on previous results and more than 5 years of research in an effort to validate a lipedema biomarker, to diagnose or monitor the progress of the disease. Additionally, pharmaceutical agents will be assessed, providing the data sets and tangible information needed to transition towards the implementation of pilot clinical studies, opening new horizons for lipedema treatment.

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