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Lipedema is a chronic, progressive disease of adipose tissue with lack of consistent diagnostic criteria. The aim of this study was a thorough comparative characterization of extracellular microRNAs (miRNAs) from the stromal vascular fraction (SVF) of healthy and lipedema adipose tissue. For this, we analyzed 187 extracellular miRNAs in concentrated conditioned medium (cCM) and specifically in small extracellular vesicles (sEVs) enriched thereof by size exclusion chromatography. No significant difference in median particle size and concentration was observed between sEV fractions in healthy and lipedema. We found the majority of miRNAs located predominantly in cCM compared to sEV enriched fraction. Surprisingly, hierarchical clustering of the most variant miRNAs showed that only sEVmiRNA profiles – but not cCMmiRNAs – were impacted by lipedema. Seven sEVmiRNAs (miR–16-5p, miR-29a-3p, miR-24-3p, miR-454-p, miR–144-5p, miR-130a-3p, let-7c-5p) were differently regulated in lipedema and healthy individuals, whereas only one cCMmiRNA (miR-188-5p) was significantly downregulated in lipedema. Comparing SVF from healthy and lipedema patients, we identified sEVs as the lipedema relevant miRNA fraction. This study contributes to identify the potential role of SVF secreted miRNAs in lipedema.

Lipedema is a chronic, progressive disease of adipose tissue with unknown etiology. Based on the relevance of the stromal vascular fraction (SVF) cell population in lipedema, we performed a thorough characterization of subcutaneous adipose tissue, SVF isolated thereof and the sorted populations of endothelial cells (EC), pericytes and cultured adipose-derived stromal/stem cells (ASC) of early-stage lipedema patients. We employed histological and gene expression analysis and investigated the endothelial barrier by immunofluorescence and analysis of endothelial permeability in vitro. Although there were no significant differences in histological stainings, we found altered gene expression of factors relevant for local estrogen metabolism (aromatase), preadipocyte commitment (ZNF423) and immune cell infiltration (CD11c) in lipedema on tissue level as well as in distinct cellular subpopulations. Machine learning analysis of immunofluorescence images of CD31 and ZO-1 revealed a morphological difference in the cellular junctions of EC cultures derived from healthy and lipedema individuals. Furthermore, the secretome of lipedema-derived SVF cells was sufficient to significantly increase leakiness of healthy human primary EC, which was also reflected by decreased mRNA expression of VE-cadherin. Here we showed for the first time, that the secretome of SVF cells creates an environment that triggers endothelial barrier dysfunction in early-stage lipedema. Moreover, since alterations in gene expression were detected on the cellular and/or tissue level, the choice of sample material is of high importance in elucidating this complex disease.

Fett bietet neben seinem volumisierenden Effekt ein reichhaltiges Reservoir fur regenerative Zellen, die eine wichtige Rolle fur den Einbau und das Uberleben eines Fettgrafts spielen. Wir haben den Unterschied zwischen dermalem weisem Fettgewebe (dWAT) und subkutanem weisem Fettgewebe (sWAT) als auch die Auswirkungen der maschinellen und manuellen Fettabnahme mit verschiedenen Kanulen- bzw. Perforationsgrosen auf die Viabilitat der Adipozyten und der aus dem Fettgewebe isolierten stromalen vaskularen Fraktion (SVF) untersucht. Zusatzlich verglichen wir, ob eine hohe Zentrifugation sowie die Tumeszenzlosung einen Effekt auf diese Zellen haben. Es zeigte sich, dass mit einer dWAT-Kanule mehr tote Adipozyten hervorgebracht werden, jedoch mit einer hoheren SVF-Zellausbeute. Die aus dWAT isolierten SVF-Zellen zeigten eine leicht erhohte Zelldichte und metabolische Aktivitat nach Isolierung im Vergleich zu aus sWAT isolierten SVF-Zellen. Im Gegensatz zur 2‑mm-Kanule war die 1‑mm-Kanule schonender in der Fettentnahme und brachte signifikant viable SVF-Zellen hervor. Einen negativen Effekt auf das Uberleben der Adipozyten zeigte unser Versuch, Fettgrafts mittels 2 Spritzen und Sieb herzustellen. Das Waschen mit NaCl, um die Tumeszenzlosung zu entfernen, resultierte in weniger toten Zellen im Liposuktionsmaterial. Auch die vielerorts verwendete Zentrifugation des Liposuktionsmaterials hatte einen negativen Einfluss auf das Uberleben der Adipozyten. Ein Eigenfetttransfer besteht aus vielen einzelnen Schritten. Das Ergebnis hangt nicht nur von der Wahl der Kanulen, sondern auch von der Verarbeitung und Reinjektionstechnik des gewonnenen Gewebes ab. Ziel ist, jeden einzelnen Verarbeitungsschritt zu verbessern, um dem transplantierten Gewebe die bestmoglichen Uberlebenschancen zu bieten und dadurch das Endergebnis zu optimieren.

BACKGROUND Lipedema is a chronic, progressive disease that occurs almost exclusively in women and leads to pathological, painful fat growths at the extremities. Only symptomatic therapy can be offered since the etiology of the disease has not yet been clarified. Liposuction in tumescent anesthesia has established itself as a surgical treatment method of choice. The complication rate associated with the procedure and the pharmacological course and safety of treatment in patients with lipedema has not yet been sufficiently studied. The aim of the study was to broaden the evidence on the safety of ambulatory high-volume liposuction in tumescent anesthesia in lipedema patients. Influencing factors of patients (weight, fat content, comorbidities) or the process technique (drug administration, volume of aspirates) should be investigated on the safety and risks of tumescent anesthesia. This was a retrospective data analysis in which data from 27 patients (40 liposuction procedures) treated at the Sandhofer and Barsch lipedema center between 2016 and 2018 were evaluated. The liposuctions were carried out in tumescent anesthesia and using a Power-Assisted Liposuction system. Clinical examinations and regular blood samples were carried out before the procedure, intra- and postoperatively. The procedures lasted an average of 118 minutes and an average of 6111 ml of aspirate was removed. For tumescent anesthesia, patients were given an average lidocaine dose of 34.23 mg/kg body weight and an epinephrine dose of 0.11 mg/kg body weight. No relevant complications associated with drug side effects, hypovolemia or hypervolemia or blood loss were detected. Liposuction under high volume tumescent anesthesia for the treatment of lipedema patients is, even for major intervention, a safe procedure. J Drugs Dermatol. 2021;20(3):326-334. doi:10.36849/JDD.5828.

Positive Effekte der extrakorporalen Stoswellentherapie (ESWT) konnten zuvor auf Wundheilung, Nervenregeneration und Gefasneubildung bewiesen werden. In dieser Studie haben wir die radiale ESWT zur Gesichtsrejuvenation untersucht, wobei bereits die direkte ESWT-Behandlung erste Wirkung gezeigt hat. Fur eine gesteigerte Volumisierung wurde zusatzlich Eigenfett mit ESWT-Vorbehandlung des Spender-und Empfangerareals appliziert. Die Vorbehandlung des Empfangerareals mit ESWT ist fur das Anwachsen des Transplantats notwendig, da mittels ESWT die Angiogenese und somit ein erfolgreicher Einbau der Grafts im Zielgewebe erfolgen kann.

Cellulite is a change of the skin and subcutaneous tissue that develops mainly in the thighs and gluteal region of almost all women. Many concepts in the pathological physiology of cellulite are to some extent contradictory and inconclusive; however, some studies point to structural changes in the dermis and subcutaneous tissue. A correlation of cellulite with focal hypertrophic subcutaneous connective tissue strands and lower density of connective tissue septa in subcutaneous tissue also point to changes in the related gluteal fascia and thus in the closely interlaced gluteal muscles. A rapid degenerative development of the muscle dynamics that were originally gained over generations unquestionably occurs in the Caucasian race and its related urbanization. The gender-specific dimorphism in the subcutaneous area must also be investigated further, since almost exclusively women are affected. For this reason we have anatomically examined male and female gluteal zones and demonstrated significant genderspecific changes. In particular, a weakening of the muscle-tendon and muscle-fascia dynamics of the gluteal muscles appears to be responsible for the round, superficially visible dermal changes. The entire embryonic unit of the muscle-fascia-skin structures in the buttocks and thigh area is involved in female cellulite. A transformation of these degenerative changes through regenerative measures, such as active movement and shock wave therapy is, therefore, appropriate and necessary.

Cellulite ist eine sich bevorzugt an den Oberschenkeln und Glutealregion beinahe bei fast allen Frauen entwickelnde Veranderung von Haut und Subkutangewebe. Viele Konzepte zur Pathophysiologie der Cellulite sind teilweise widerspruchlich und unschlussig. Einige Studien weisen jedoch auf strukturelle Veranderungen an Dermis und Subkutangewebe hin. Eine Korrelation von Cellulite mit fokalen hypertrophen subkutanen Bindegewebsstrangen und verringerter Dichte der Bindegewebssepten im Subkutangewebe weist auch auf Veranderungen der damit verbundenen Fascia glutealis und mit der dabei eng verwobenen Glutealmuskulatur hin. Fraglos besteht bei der kaukasischen Rasse und der mit ihr verbundenen Urbanisierung eine rapide degenerative Entwicklung der ursprunglich uber Generationen erworbenen Muskeldynamik. Auch ist der geschlechtsspezifische Dimorphismus im subkutanen Bereich genauer zu untersuchen, zumal fast ausschlieslich Frauen betroffen sind. Aus diesem Grund haben wir mannliche und weibliche Gesaszonen anatomisch untersucht und hierbei deutliche geschlechtsspezifische Veranderungen aufzeigen konnen. Vor allem eine Abschwachung der myotendinosen und myofaszialen Dynamik der Glutealmuskulatur scheint fur die runden, oberflachlich sichtbaren dermalen Veranderungen verantwortlich zu sein. Die embryologische Einheit der muskulofasziokutanen Strukturen im Gesas und Oberschenkelbereich ist als Gesamtes bei der weiblichen Cellulite involviert. Daher ist eine Transformation dieser degenerativen Veranderungen durch regenerative Masnahmen wie aktive Bewegung und Stoswelle sinnvoll und notwendig.

Regenerative Zellen werden zur Gewebekonstruktion und -regeneration genutzt. Dabei hat sich Fettgewebe als Quelle aufgrund guter Verfugbarkeit und leichter Gewinnung in der kosmetischen und plastischen Chirurgie durchgesetzt. Jedoch gibt es bei der Aufbereitung des zu transplantierenden Zellgemischs einiges zu beachten.

One of the mainstays of facial rejuvenation strategies is volume restoration, which can be achieved by autologous fat grafting. In our novel approach, we treated the adipose tissue harvest site with extracorporeal shock wave therapy (ESWT) in order to improve the quality of the regenerative cells in situ. The latter was demonstrated by characterizing the cells of the stromal vascular fraction (SVF) in the harvested liposuction material regarding cell yield, adenosine triphosphate (ATP) content, proliferative capacity, surface marker profile, differentiation potential and secretory protein profile. Although the SVF cell yield was only slightly enhanced, viability and ATP concentration of freshly isolated cells as well as proliferation doublings after 3 weeks in culture were significantly increased in the ESWT compared with the untreated group. Likewise, cells expressing mesenchymal and endothelial/pericytic markers were significantly elevated concomitant with an improved differentiation capacity towards the adipogenic lineage and enhancement in specific angiogenic proteins. Hence, in situ ESWT might be applied in the future to promote cell fitness, adipogenesis and angiogenesis within the fat graft for successful facial rejuvenation strategies with potential long-term graft survival.

Background aims Lipedema is a hormone-related disease of women characterized by enlargement of the extremities caused by subcutaneous deposition of adipose tissue. In healthy patients application of autologous adipose tissue–derived cells has shown great potential in several clinical studies for engrafting of soft tissue reconstruction in recent decades. The majority of these studies have used the stromal vascular fraction (SVF), a heterogeneous cell population containing adipose-derived stromal/stem cells (ASC), among others. Because cell identity and regenerative properties might be affected by the health condition of patients, we characterized the SVF cells of 30 lipedema patients in comparison to 22 healthy patients. Methods SVF cells were analyzed regarding cell yield, viability, adenosine triphosphate content, colony forming units and proliferative capacity, as well as surface marker profile and differentiation potential in vitro. Results Our results demonstrated a significantly enhanced SVF cell yield isolated from lipedema compared with healthy patients. In contrast, the adipogenic differentiation potential of SVF cells isolated from lipedema patients was significantly reduced compared with healthy patients. Interestingly, expression of the mesenchymal marker CD90 and the endothelial/pericytic marker CD146 was significantly enhanced when isolated from lipedema patients. Discussion The enhanced number of CD90+ and CD146+ cells could explain the increased cell yield because the other tested surface marker were not reduced in lipedema patients. Because the cellular mechanism and composition in lipedema is largely unknown, our findings might contribute to a better understanding of its etiology.

Lipedema is a chronic, progressive disease of adipose tissue with lack of consistent diagnostic criteria. The aim of this study was a thorough comparative characterization of extracellular microRNAs from the stromal vascular fraction (SVF) of healthy and lipedema adipose tissue. For this, we analyzed 187 extracellular microRNAs in concentrated conditioned media (cCM) and specifically in small extracellular vesicles (sEVs) enriched thereof by size exclusion chromatography. No significant difference in median particle size and concentration was observed between sEV fractions in healthy and lipedema. We found the majority of miRNAs located predominantly in cCM compared to sEV enriched fraction. Surprisingly, hierarchical clustering of the most variant miRNAs showed that only sEV miRNA profiles – but not cCM miRNAs – were impacted by lipedema. Seven sEV miRNAs (miR–16-5p, miR-29a-3p, miR-24-3p, miR-454-p, miR–144-5p, miR-130a-3p, let-7c-5p) were differently regulated in lipedema and healthy, whereas only one cCM miRNA (miR-188-5p) was significantly downregulated in lipedema. Comparing SVF from healthy and lipedema patients, we identified sEVs as the lipedema relevant miRNA fraction. This study contributes to identify the potential role of SVF secreted miRNAs in lipedema.

Lipedema is a chronic, progressive disorder of subcutaneous adipose tissue that usually affects the lower extremities of women. Also known as "two-body syndrome," the fat accumulations in lipedema are unsightly and painful. The disorder is well-known in Europe but is largely unrecognized and underdiagnosed in the United States.To hold the First International Consensus Conference on Lipedema with the purpose of reviewing current European guidelines and the literature regarding the long-term benefits that have been reported to occur after lymph-sparing liposuction for lipedema using tumescent local anesthesia.International experts on liposuction for lipedema were convened as part of the First International Congress on Lipedema in Vienna, Austria, June 9 to 10, 2017.Multiple studies from Germany have reported long-term benefits for as long as 8 years after liposuction for lipedema using tumescent local anesthesia.Lymph-sparing liposuction using tumescent local anesthesia is currently the only effective treatment for lipedema.

BACKGROUND Cryolipolysis combined with shockwave therapy has been previously shown to have synergistic effects in body contouring results. OBJECTIVE This open-label, prospective, multicenter, comparative study investigated the safety and efficacy of combined cryolipolysis, shockwave therapy with cryolipolysis, shockwave therapy, and injection polyenylphosphatidylcholine-based lipolysis. METHODS Enrolled patients were treated in the abdominal or flank area with cryolipolysis, shockwave therapy and injection lipolysis (n = 10) or cryolipolysis and shockwave therapy (n = 4). All treatments were conducted the same day. Evaluations were conducted 3 months after treatment and included histological analysis, standardized photography, blinded-investigator efficacy, and safety ratings, as well as patient ratings of satisfaction and tolerance. RESULTS Compared to baseline, the 3-month follow-up histological analysis revealed a more profound subcutaneous adipose tissue reaction with the triple combination therapy (cryolipolysis, injection lipolysis, radial shock wave) than with the double combination with regard to adipocyte damage and grade of inflammation. Waist circumference was significantly reduced in patients of both groups, but patients in the triple combination group were shown to have a significantly more pronounced reduction in subcutaneous fat. Factors that were shown to influence treatment outcome included baseline BMI and waist circumference. Age and gender had no effect. The abdominal area reacted better to the treatment compared to flanks. No significant side effects or adverse events were reported. The procedure was well-tolerated, and the majority of patients were satisfied with the treatment results. CONCLUSIONS Combination of cryolipolysis, radial shockwave, and injection lipolysis is a safe, well-tolerated treatment for reduction in subcutaneous fat.

Das Integumentum mit seinen dermalen und subkutanen Komponenten hat in den letzten Jahren ein enormes Interesse in Forschung und Klinik hervorgerufen. Die Adipositas hat sich epidemieartig mit allen ihren Problemen in der Ersten Welt als Seuche etabliert. Andererseits hat sich die Fettabsaugung mit allen ihren Indikationen zum haufigsten asthetischen Eingriff entwickelt. Als Nebenprodukt dieser Methode hat sich das Fett als sehr potente Quelle fur die Gewinnung von mesenchymalen Stammzellen fur die regenerative Medizin gezeigt. Diese Stammzellen sind anatomischen Nischen zugeordnet und sorgen hier fur die Aufrechterhaltung, Reparatur und Neubildung des Gewebes.

Adipozyten sind in verschiedenen Nischen mit unterschiedlichen anatomischen Funktionen organisiert. Das dermale Fettgewebe („dermal white adipose tissue“, dWAT), das an der Grenze zwischen ektodermalen und mesodermalen Schichten lokalisiert ist, erfullt spezifische Funktionen bei der Oberflachenprofilierung. Diese Fraktion ist einfach zu gewinnen und sollte zur oberflachlichen Augmentation eingesetzt werden. Fettgewebe sollte in kleinen Portionen appliziert werden. Die Replantationsergebnisse mit einfachem frisch gewonnenem Fett sind erfolgreich, sodass regenerative Verfahren nicht notig sind.

Silicone gel has for many years had a primary role in the treatment and prevention of abnormal scars, in the form of hypertrophic scars and keloids after epithelialization. The authors report preliminary findings on the use of a new, medical-grade, film-forming silicone gel dressing approved for use on open wounds and injured skin as monotherapy and in combination with other treatments prior to re-epithelialization. An observational study involving 105 patients examined the silicone gel's effectiveness in promoting accelerated epithelialization, reducing the inflammatory response and in the prevention of scarring. The study was conducted on a range of dermatological surgical interventions. The authors' observations confirmed silicone's role in promoting accelerated wound healing, scar prevention, and the utility of this new film-forming silicone dressing when used in combination with various other treatment modalities.