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Genetic or acquired defects of the lymphatic vasculature often result in disfiguring, disabling, and, occasionally, life-threatening clinical consequences. Advanced forms of lymphedema are readily diagnosed clinically, but more subtle presentations often require invasive imaging or other technologies for a conclusive diagnosis. On the other hand, lipedema, a chronic lymphatic microvascular disease with pathological accumulation of subcutaneous adipose tissue, is often misdiagnosed as obesity or lymphedema; currently there are no biomarkers or imaging criteria available for a conclusive diagnosis. Recent evidence suggests that otherwise-asymptomatic defective lymphatic vasculature likely contributes to an array of other pathologies, including obesity, inflammatory bowel disease, and neurological disorders. Accordingly, identification of biomarkers of lymphatic malfunction will provide a valuable resource for the diagnosis and clinical differentiation of lymphedema, lipedema, obesity, and other potential lymphatic pathologies. In this paper, we profiled and compared blood plasma exosomes isolated from mouse models and from human subjects with and without symptomatic lymphatic pathologies. We identified platelet factor 4 (PF4/CXCL4) as a biomarker that could be used to diagnose lymphatic vasculature dysfunction. Furthermore, we determined that PF4 levels in circulating blood plasma exosomes were also elevated in patients with lipedema, supporting current claims arguing that at least some of the underlying attributes of this disease are also the consequence of lymphatic defects., , Characterization of plasma-circulating exosomes from mouse models and patients with lymphatic dysfunction indicate that PF4 is a promising biomarker for the diagnosis of lymphatic disorders.

In recent years stem cell research has become increasingly important for regenerativemedicine and tissue engineering. The isolation of stem cells from adipose tissue evades ethicalconcerns with which embryonic stem cells and induces pluripotent stem cells (iPS) are afflicted,because of its declaration as clinical waste material. Tumescent liposuction is a minimallyinvasive procedure providing high amounts of adipose tissue rich in therapeutically relevantcells within a short time. The isolated stromal vascular fraction (SVF) and the adipose derivedstromal/stem cells (ASC) contained therein show a high regenerative potential and have beensuccessfully used in many clinical studies. Maintaining SVF cells in their natural environmentand therefore providing the maximum possible regenerative potential of adipose tissue-derivedcells is a prerequisite for successful autologous clinical application. With an improved gentleand fast isolation process by minor manipulation it is possible to obtain a therapeuticallyrelevant cell population. A physical stimulus already used in clinics is the extracorporealshockwave therapy (ESWT), shockwaves are characterized by their high rise in pressurewithin a very short time followed by cavitation wave with a negative amplitude. By applyinglow-energy ESWT on freshly obtained human liposuction material and isolated SVF cells (invitro) we aimed to equalize and enhance stem cell properties and their functionality. We wereable to show an increased adenosine tri-phosphate (ATP) concentration after applying ESWTon adipose tissue as well as a significantly increased expression of single mesenchymal andvascular surface markers in comparison with the untreated group. Additionally, the proteinsecretion of insulin-like growth factor 1 (IGF-1) and placental growth factor (PLGF) wassignificantly enhanced. Further it was investigated if there is the same beneficial effect whenapplying ESWT on the adipose tissue harvest site before liposuction to improve cell propertiesin situ. We showed a significantly enhanced viability, ATP concentration and populationdoublings after 3 weeks in culture for cells isolated from ESW treated adipose tissue harvestsite. Further the expression of mesenchymal and endothelial/pericytic markers was elevatedcollaborating with the increased angiogenic differentiation potential as well as the increasedsecretion of certain angiogenic proteins after ESWT in situ. Besides ESWT the effect of anotherphysical stimulus on SVF/ASC cells was tested - Low level laser therapy (LLLT) has alreadyshown beneficial effects. Therefore, we investigated effects of pulsed blue (475nm), green(516nm) and red (635nm) light from light-emitting diodes (LEDs) applied on freshly isolatedSVF cells. Cells had a stronger capacity to vascular tube formation after exposure to greenand red light concomitant with an increased concentration of vascular endothelial growth factor(VEGF) in the secretome. In a side project during the PhD program the hormone-relatedwomens disease lipedema was investigated. The SVF cell properties of healthy and lipedemapatients were investigated and a significant enhancement in cell yield as well as a reduction inadipogenic differentiation capacity of lipedema SVF cells was revealed. Within this workdifferent physical forces applied on adipose tissue and adipose tissue-derived cells werepresented as well as an improved isolation method and characteristics of degenerated adiposetissue. This are promising applications for the clinical use in the field of regenerative medicineand tissue regeneration.

The objective of the present study was to report that aggravating factors of lymphatic or venous edema contribute to aggravate the evolution of lymphedema. A 54-year-old women with a six-year history of venous thrombosis of the left leg reported that her family had thicker arms and legs and that she had inherited this genetic trait. Electrical bioimpedance analysis was performed with the In Body S10 device. The exam revealed total intracellular and extracellular water beyond the parameters of normality as well as water in the thorax and limbs. In the lower limbs, the total extracellular water/total body water ratio also surpassed the limits of normality. The findings demonstrated bilateral lower limb lymphedema with clinical signs in the left leg. Obesity can trigger a new concept of lymphedema that we denominate subclinical systemic lymphedema, which is characterized by an increase in body water. Moreover, aggravating processes of the venous system, such as deep vein thrombosis, can aggravate the edema.

Aim: The aim of the present study was to evaluate the prevalence of subclinical and clinical systemic lymphedema in patients with lipedema and different body mass index (BMI) values., Method: A cross-sectional study was conducted to determine the prevalence of subclinical systemic lymphedema and clinical lymphedema of the lower limbs detected by bioimpedance (InBody S10 device, Seoul, Korea) in 258 women with clinically diagnosed lipedema. The patients were divided into three groups based on BMI: Group I - BMI below 30 kg/m2; Group II - BMI between 30 and 40 kg/m2; and Group III - BMI 40 to 50 kg/m2., Results: Fisher's exact test revealed a statistically significant difference between Group I and both Groups II and III (p = 0.0001) regarding the occurrence of lower limb lymphedema., Conclusion: Patients with lipedema can develop edema even when their weight is within the standards of normality. However, obesity is an aggravating factor, as the prevalence of lipedema increases progressively with the increase in weight.

Summary Lipedema is a painful, chronically progressive disease that is characterized by a symmetrical increase in subcutaneous fat with fluid accumulation on the legs and / or arms. Due to ignorance of the clinical picture, the disease is often not recognized or misinterpreted. Correct diagnosis and treatment are important, however, as the prognosis of the disease can be influenced. A causal therapy for lipedema is not known because the exact etiology is not yet fully understood. A hereditary component is suspected on the basis of a family history of the disease. Since lipedema occurs almost exclusively in women and the onset of the disease is often associated with the onset of hormonal changes (puberty, pregnancy, menopause), In addition, the estrogen is assigned a decisive role in the development. In the present work we present an overview of the symptoms and clinical features of lipedema, its differential diagnoses, treatment options and, lastly, the current hypotheses on the pathogenesis of lipedema.

IN JUNE 2020, the Lipedema ICD-10-CM Committee, with support from the American Vein & Lymphatic Society (AVLS), submitted an application to the US Centers for Disease Control and Prevention to establish new ICD-10-CM codes for lipedema and lipolymphedema, two related adipose tissue disorders. Currently,

Patients with obesity-associated lipoedema minimize by diet only the regular fat especially in the lower leg area. The pathological lipoedema with a possible secondary lymphodynamic oedema remains and causes skin irritation, discomfort and pain wearing the compression elements. The dorsal lower leg lift with previous liposuction is a useful therapeutic strategy to overcome these difficulties. A 37-year-old female patient after post-bariatric surgery and massive weight loss (MWL) presented with a lower leg lipoedema and lymphodynamic oedema. She underwent a liposuction removing lipoedema of the lower leg followed by a calf lift procedure on both sides. With sufficient surgical experience in skin tightening surgery after MWL, a significant improvement in day-to-day problems in patients with lipoedema can be achieved by dorsal lift of the lower leg after liposuction.