3D Spheroids Derived from Human Lipedema ASCs Demonstrated Similar Adipogenic Differentiation Potential and ECM Remodeling to Non-Lipedema ASCs In Vitro

Al-Ghadban, Sara; Pursell, India; Diaz, Zaidmara; Herbst, Karen L.; Bunnell, Bruce A.

doi:10.3390/ijms21218350

Cited by 19 publications

(31 citation statements)

References 59 publications

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“…ASCs derived from lipedema tissues exhibited a distinct gene expression compared to controls [ 88 ]. Similar but slightly elevated adipogenic gene expression between lipedema and control samples was noted in an in vitro 3D matrix of ASCs (so-called spheroids), characterizing the adipogenic potential in lipedema pathology [ 90 ]. In lymphedema, adipose deposition occurs with persistent inflammation and thus, postulates whether a source of inflammation is also present in lipedema.…”

Section: Molecular Regulators and Pathophysiologymentioning

confidence: 89%

“…An intriguing hypothesis for lipedema pathogenesis involves improper ECM remodeling, whereby uncoupling of the MMP-14-caveolin 1 (CAV1) axis in adipocytes may cause aberrant matrix processing, resulting in hypertrophic SAT expansion [ 97 ]. Initial studies into this pathophysiologic mechanism found slightly lower expressions of MMP-2, -9, and -11 in a cohort of patients with lipedema compared to controls, with no significant difference in ECM fibronectin or collagen [ 90 ]. Changes to the ECM or the compliance of connective tissue would be interesting to study in relation to patient symptomatology of joint hypermobility, as well as findings of reduced elasticity of the skin [ 98 ] and aorta [ 99 ] in some patients with lipedema.…”

Section: Molecular Regulators and Pathophysiologymentioning

confidence: 99%

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Current Mechanistic Understandings of Lymphedema and Lipedema: Tales of Fluid, Fat, and Fibrosis

Duhon¹,

Phan²,

Taylor

et al. 2022

IJMS

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Lymphedema and lipedema are complex diseases. While the external presentation of swollen legs in lower-extremity lymphedema and lipedema appear similar, current mechanistic understandings of these diseases indicate unique aspects of their underlying pathophysiology. They share certain clinical features, such as fluid (edema), fat (adipose expansion), and fibrosis (extracellular matrix remodeling). Yet, these diverge on their time course and known molecular regulators of pathophysiology and genetics. This divergence likely indicates a unique route leading to interstitial fluid accumulation and subsequent inflammation in lymphedema versus lipedema. Identifying disease mechanisms that are causal and which are merely indicative of the condition is far more explored in lymphedema than in lipedema. In primary lymphedema, discoveries of genetic mutations link molecular markers to mechanisms of lymphatic disease. Much work remains in this area towards better risk assessment of secondary lymphedema and the hopeful discovery of validated genetic diagnostics for lipedema. The purpose of this review is to expose the distinct and shared (i) clinical criteria and symptomatology, (ii) molecular regulators and pathophysiology, and (iii) genetic markers of lymphedema and lipedema to help inform future research in this field.

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Section: Molecular Regulators and Pathophysiologymentioning

confidence: 89%

Section: Molecular Regulators and Pathophysiologymentioning

confidence: 99%

Current Mechanistic Understandings of Lymphedema and Lipedema: Tales of Fluid, Fat, and Fibrosis

Duhon¹,

Phan²,

Taylor

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…The accumulation of lipids and other light-scattering agents in multiple layers of cells within tissue presents a major hurdle to visualise the same biology in spheroids and organoids. Studies investigating extracellular matrix composition in spheroids [ 64 ] and evaluation of tight junctions in human intestinal organoids, have used cryosections [ 65 ] and immunohistochemistry to define the architecture and distribution of multiple markers (e.g., colorectal cancer [ 66 ] and corneal limbal organoids [ 67 ]). By performing serial sections, the structure may be re-created to reveal significant information about tissue; however, efficiency may be increased if antibody labelling and imaging could be performed on a minimally processed, intact organoid.…”

Section: Biological Models For Fluorescence Imaging; From the Monolayer Culture To The Whole Organmentioning

confidence: 99%

Fluorescence Microscopy—An Outline of Hardware, Biological Handling, and Fluorophore Considerations

Hickey

Ung

Bader

et al. 2021

Cells

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Fluorescence microscopy has become a critical tool for researchers to understand biological processes at the cellular level. Micrographs from fixed and live-cell imaging procedures feature in a plethora of scientific articles for the field of cell biology, but the complexities of fluorescence microscopy as an imaging tool can sometimes be overlooked or misunderstood. This review seeks to cover the three fundamental considerations when designing fluorescence microscopy experiments: (1) hardware availability; (2) amenability of biological models to fluorescence microscopy; and (3) suitability of imaging agents for intended applications. This review will help equip the reader to make judicious decisions when designing fluorescence microscopy experiments that deliver high-resolution and informative images for cell biology.

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“…Specifically, we demonstrated that it was possible to isolate from human adipose tissue a population of adipose-derived stem cells (ASC) that not only could be a valuable source for regenerative medicine [23][24][25] but also, when isolated from patients affected by human Nieman Pick C disease, could represent an in vitro model resembling the features of diseased cells [17]. A similar approach has been recently utilized to create an in vitro model of lipedema [26,27].…”

Section: Introductionmentioning

confidence: 99%

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

Caponnetto

Manini

Bulfoni

et al. 2020

Cells

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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.

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3D Spheroids Derived from Human Lipedema ASCs Demonstrated Similar Adipogenic Differentiation Potential and ECM Remodeling to Non-Lipedema ASCs In Vitro

Cited by 19 publications

References 59 publications

Current Mechanistic Understandings of Lymphedema and Lipedema: Tales of Fluid, Fat, and Fibrosis

Current Mechanistic Understandings of Lymphedema and Lipedema: Tales of Fluid, Fat, and Fibrosis

Fluorescence Microscopy—An Outline of Hardware, Biological Handling, and Fluorophore Considerations

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

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