Project: Extracellular Matrix Remodeling in Lipedema

Principal Investigator: Ngan F. Huang, PhD
Associate Professor, Department of Cardiothoracic Surgery
Stanford University

Principal Investigator, Veterans Affairs
Palo Alto Health Care System
Palo Alto, CA

Co-Principal Investigator: Bruce Alan Bunnell, PhD
University of North Texas Health Center
Fort Worth, TX

Summary

This research explores the role of the extracellular matrix (ECM) in influencing the adipose tissue of lipedema donors. The global hypothesis is that Lipedema adipose tissue has pathologically altered ECM properties that modulate the phenotype and function of adipose stromal cells (ASCs) in Lipedema patients.

Background

The gaps in knowledge that will be addressed include 1) the pathological changes in the adipose tissue ECM properties in adipose tissue from Lipedema donors, compared to non-diseased adipose tissue; 2) how pathological changes in ECM associated lipedema modulate ASC phenotype and function; and 3) the identification of ECM proteins as Lipedema biomarkers. We further develop a tissue chip platform to study whether differential ECM environments can induce or reverse ASC dysfunction associated with Lipedema.

Methodology

First, we will purify the ECM from adipose tissue from Lipedema o non-diseased  donors and then quantitatively compare the relative abundance of ECM proteins between them. The purified ECMs will then be subjected to tandem mass spectroscopy to identify the ECMs and their relative abundance. The findings from mass spectroscopy will be further verified by immunoblotting. Next, we will examine how an ECM composition associated with Lipedema modulates ASC phenotype and differentiation capacity in vitro. 

Based on the composition and ECM composition associated with Lipedema adipose tissue, we will create an ECM chip consisting of Lipedema or non-diseased ECM signatures.  Both healthy and Lipedema donor-derived ASCs will be cultured on the ECM chip for assessment of proliferation, multipotency, and adipogenic differentiation capacity. Finally, we will examine how an ECM signature associated with Lipedema influences the inflammatory cytokine secretion between ASCs from Lipedema or non-diseased donors.

Expected outcomes

The primary objective is to quantitatively compare the ECM properties of adipose tissue derived from either clinical Lipedema or non-diseased donors. The global hypothesis is that Lipedema adipose tissue has pathologically altered ECM properties that modulate the phenotype and function of ASCs in Lipedema patients. 

The anticipated outcomes include a compendium of ECM protein abundances associated with Lipedema, along with the resulting differential in vitro effects on ASC phenotype, differentiation, and cytokine production.

Practical implementations of results

These studies will reveal quantitative differences in the ECM properties of adipose tissue between Lipedema and non-diseased donors. From these studies, a “Lipedema ECM signature” will be revealed for the first time as a potential biomarker for future diagnostic testing or as a therapeutic target.  We anticipate that the fundamental knowledge gained will advance the treatment and care for patients with Lipedema.

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