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Introduction: Lipedema is a fat disorder in which high levels of inflammation and over proliferative adipocytes lead to accumulation of adipose tissue in peripheral limbs. Lipedema is intertwined with lymphedema, in which patients with advanced stages of lipedema often develop secondary lymphedema. The adipose tissue extracellular matrix (ECM) modulates the function of adipocytes and adipose stromal cells (ASCs). In lipedema, the aberrant adipose tissue is characterized by stiff and fibrotic nodules, suggesting changes in biochemical and mechanical properties. It is unknown how the biomechanical and biochemical composition of the ECM affects lipedema. Thus, we have developed a tissue chip format using various ECMs and stiffnesses to evaluate their effects on ASCs from both lipedema and non-lipedema patients.Hypothesis: Lipedema donor-derived ASCs have higher proliferation compared to non-lipedema cells, and stiffer substrates will have higher proliferation rates compared to softer substrates.Methods: Tissue chips were fabricated using 64 well microscale formats. Polydimethylsiloxane substrates were fabricated with three stiffnesses (150, 500, and 900 kPa). Upon surface modification by polydopamine, 31 different multi-component ECM combinations consisting of collagens 2-4, fibronectin, and laminin were immobilized. Human ASCs from lipedema or non-lipedema patients were seeded onto tissue chips (n=3), cultured for 48h, fixed, and then stained Ki67 as a proliferation marker. Ki67 expression was quantified using cellprofiler software and analyzed using R.Results and Conclusions: ASCs from non-lipedema donors showed higher Ki67 expression, compared to lipedema donors, indicating higher degree of proliferation. Additionally, 150 kPa substrates showed higher rates of proliferation compared to 900 kPa substrates, while 500 kPa substrates had moderate proliferation rates in between the other two stiffnesses. To a lesser extent, the ECM biochemical composition further influenced proliferation capacity. Contrary to our hypothesis, non-lipedema ASCs had higher proliferation rates than lipedema ASCs, and softer substrates had higher rates of proliferation than stiffer substrates. As lipedema adipocytes are hypertrophic, we expected that lipedema derived ASCs would have higher rates of proliferation compared to non-lipedema ASCs. Additional analysis of other metrics of lipedema (ie inflammation) and further interrogation of lymphatic function are warranted.Open in Viewer
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Lipedema is a chronic adipose tissue condition that primarily affects women. Despite increasing recognition of lipedema, the condition remains poorly understood and lacks standardized diagnostic criteria or confirmatory tests. Variability in definitions and measurement across clinical and research settings impedes comparability across studies, constraining the evidence base needed to support future advances in clinical practice and patient care. To address challenges associated with inconsistent definitions and data collection, the Lipedema Foundation (LF) partnered with clinicians, researchers, and biostatisticians to develop a Lipedema Common Case Report Form (CCRF). The CCRF was designed to be a research data harmonization tool and is not intended to define diagnostic standards or guide clinical treatment decisions. Its development involved review of published lipedema clinical guidelines and collaborative work to define data elements and attributes for inclusion. When they existed, validated or standardized measures were incorporated directly. When no suitable standardized measures were available, an iterative and collaborative process was used to develop lipedema-specific Common Data Elements (CDEs). The initial version of the CCRF was piloted in participants with and without lipedema, and updates based on participant and clinician feedback were incorporated into the CCRF. A biostatistical review evaluated data completeness, quality, and structure, leading to additional refinements. The final Version 1 instrument consists of 682 CDEs organized into four classifications: (1) Core, (2) Supplemental Highly Recommended, (3) Supplemental, and (4) Exploratory. The current version is prepared for dissemination in the field. By disseminating the CCRF broadly and encouraging adoption in all lipedema research beginning in 2026, including all newly initiated LF-funded projects, LF intends to evaluate its use with grantees and iterate systematically to achieve consistent and comparable data collection. The CCRF provides a structured framework for harmonized data collection that may facilitate comparability across studies and support future development of standardized diagnostic and research methodologies.