Human Adipose-Derived Stem Cells in Madelung’s Disease: Morphological and Functional Characterization

Abstract

Madelung Disease (MD) is a syndrome characterized by the accumulation of aberrant symmetric adipose tissue deposits. The etiology of this disease is yet to be elucidated, even though the presence of comorbidities, either genetic or environmental, has been reported. For this reason, establishing an in vitro model for MD is considered crucial to get insights into its physiopathology. We previously established a protocol for isolation and culture of stem cells from diseased tissues. Therefore, we isolated human adipose-derived stem cells (ASC) from MD patients and compared these cells with those isolated from healthy subjects in terms of surface phenotype, growth kinetic, adipogenic differentiation potential, and molecular alterations. Moreover, we evaluated the ability of the MD-ASC secretome to affect healthy ASC. The results reported a difference in the growth kinetic and surface markers of MD-ASC compared to healthy ASC but not in adipogenic differentiation. The most commonly described mitochondrial mutations were not observed. Still, MD-ASC secretome was able to shift the healthy ASC phenotype to an MD phenotype. This work provides evidence of the possibility of exploiting a patient-based in vitro model for better understanding MD pathophysiology, possibly favoring the development of novel target therapies.

Madelung’s Disease: Analysis of Clinical Characteristics, Fatty Mass Distribution, Comorbidities and Treatment of 54 Patients in China

“…There are various hypotheses about the pathophysiological mechanism of MD, including catecholamine-stimulated lipolysis disorder and mitochondrial regulation defects in brown fat. 4,[25][26][27] Long-term alcohol abuse has been considered the cause of MD in previous studies, but the specific mechanism has not been fully elucidated. [4][5][6][7] As a cofactor, alcohol has a direct impact on the metabolic process of mitochondria.…”

A case report of Madelung's disease in China

“…The etiology of Madelung's disease may be related to chronic alcohol consumption, endocrine disorders, liver disease, upper respiratory tract malignancies, chromosomal inheritance [9] , and metabolic syndromes such as hyperuricemia and hyperlipidemia type 2 diabetes mellitus and hypothyroidism signs [10] . Although the pathogenesis of Madelung's disease is still unclear, it may be related to adipose tissue mitochondrial dysfunction, decreased cytochrome C oxidase activity, catecholamine-induced fat deposition, and reduced inducible nitric oxide synthase (iNOS) [11] .…”

Lipedema: The Use of Cultured Adipocytes for Identification of Diagnostic Markers

“…[7][8][9][10] Thus, knowledge concerning the behavior and molecular alterations of adipose tissue-derived stromal/stem cells (ASCs) not only contributes to the understanding of adipose tissue-related pathologies, but also could be helpful in development of stem cell-based therapies for lipedema and other types of adipose-related diseases. [11][12][13] Concerning lipedema, most of the data available so far have emerged from studies using cultured human ASCs, in vitro differentiated adipocytes, biopsied subcutaneous adipose tissue, and the stromal vascular fraction from donors with and without lipedema. Taken together, it may be concluded that lipedema manifests at various levels, including alterations of the blood and lymphatic microvasculature, adipocyte hypertrophy and hyperplasia, tissue fibrosis, inflammation, and pain development, [14][15][16][17][18][19][20] which adds a considerable level of complexity to its pathology.…”

“…7–10 Thus, knowledge concerning the behavior and molecular alterations of adipose tissue–derived stromal/stem cells (ASCs) not only contributes to the understanding of adipose tissue–related pathologies, but also could be helpful in development of stem cell–based therapies for lipedema and other types of adipose-related diseases. 11–13…”