Adenoviral-Mediated Gene Transfer to Human Adipocytes In Vitro, and Human Adipose Tissue Ex Vivo and Rabbit Femoral Adipose Tissue In Vivo.

The therapeutic potential of mesenchymal stromal/stem cells (MSC) for treating cardiac ischemia strongly depends on their paracrine-mediated effects and their engraftment capacity in a hostile environment such as the infarcted myocardium. Adipose tissue-derived stromal vascular fraction (SVF) cells are a mixed population composed mainly of MSC and vascular cells, well known for their high angiogenic potential. A previous study showed that the angiogenic potential of SVF cells was further increased following their in vitro organization in an engineered tissue (patch) after perfusion-based bioreactor culture. This study aimed to investigate the possible changes in the cellular SVF composition, in vivo angiogenic potential, as well as engraftment capability upon in vitro culture in harsh hypoxia conditions. This mimics the possible delayed vascularization of the patch upon implantation in a low perfused myocardium. To this purpose, human SVF cells were seeded on a collagen sponge, cultured for 5 days in a perfusion-based bioreactor under normoxia or hypoxia (21% and <1% of oxygen tension, respectively) and subcutaneously implanted in nude rats for 3 and 28 days. Compared to ambient condition culture, hypoxic tension did not alter the SVF composition in vitro, showing similar numbers of MSC as well as endothelial and mural cells. Nevertheless, in vitro hypoxic culture significantly increased the release of vascular endothelial growth factor (p < 0.001) and the number of proliferating cells (p < 0.00001). Moreover, compared to ambient oxygen culture, exposure to hypoxia significantly enhanced the vessel length density in the engineered tissues following 28 days of implantation. The number of human cells and human proliferating cells in hypoxia-cultured constructs was also significantly increased after 3 and 28 days in vivo, compared to normoxia. These findings show that a possible in vivo delay in oxygen supply might not impair the vascularization potential of SVF- patches, which qualifies them for evaluation in a myocardial ischemia model.

Download Full-text

Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo

Gut ◽

10.1136/gut.2008.154880 ◽

2008 ◽

Vol 58 (4) ◽

pp. 570-581 ◽

Cited By ~ 223

Author(s):

H Aurich ◽

M Sgodda ◽

P Kaltwasser ◽

M Vetter ◽

A Weise ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Human Adipose Tissue ◽

Hepatocyte Differentiation ◽

Adipose Tissue In Vitro

Download Full-text

Human Adipose-Derived Stromal/Stem Cell Culture and Analysis Methods for Adipose Tissue Modeling In Vitro: A Systematic Review

Cells ◽

10.3390/cells10061378 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1378

Author(s):

Peyton Gibler ◽

Jeffrey Gimble ◽

Katie Hamel ◽

Emma Rogers ◽

Michael Henderson ◽

...

Keyword(s):

Systematic Review ◽

Adipose Tissue ◽

Drug Discovery ◽

3D Culture ◽

Human Adipose Tissue ◽

Culture Methods ◽

Adipose Tissue Engineering ◽

The Impact

Human adipose-derived stromal/stem cells (hASC) are widely used for in vitro modeling of physiologically relevant human adipose tissue. These models are useful for the development of tissue constructs for soft tissue regeneration and 3-dimensional (3D) microphysiological systems (MPS) for drug discovery. In this systematic review, we report on the current state of hASC culture and assessment methods for adipose tissue engineering using 3D MPS. Our search efforts resulted in the identification of 184 independent records, of which 27 were determined to be most relevant to the goals of the present review. Our results demonstrate a lack of consensus on methods for hASC culture and assessment for the production of physiologically relevant in vitro models of human adipose tissue. Few studies have assessed the impact of different 3D culture conditions on hASC adipogenesis. Additionally, there has been a limited use of assays for characterizing the functionality of adipose tissue in vitro. Results from this study suggest the need for more standardized culture methods and further analysis on in vitro tissue functionality. These will be necessary to validate the utility of 3D MPS as an in vitro model to reduce, refine, and replace in vivo experiments in the drug discovery regulatory process.

Download Full-text

In Vitro and in Vivo Calcitonin I Gene Expression in Parenchymal Cells: A Novel Product of Human Adipose Tissue

Endocrinology ◽

10.1210/en.2003-0854 ◽

2003 ◽

Vol 144 (12) ◽

pp. 5578-5584 ◽

Cited By ~ 176

Author(s):

Philippe Linscheid ◽

Dalma Seboek ◽

Eric S. Nylen ◽

Igor Langer ◽

Mirjam Schlatter ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Human Adipose Tissue ◽

Parenchymal Cells ◽

I Gene

Download Full-text

Enhanced triglyceride clearance with intraperitoneal human acylation stimulating protein in C57BL/6 mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1999.277.3.e474 ◽

1999 ◽

Vol 277 (3) ◽

pp. E474-E480 ◽

Cited By ~ 32

Author(s):

Ian Murray ◽

Allan D. Sniderman ◽

Katherine Cianflone

Keyword(s):

Adipose Tissue ◽

Area Under The Curve ◽

Human Adipose Tissue ◽

Plasma Triglyceride ◽

Complement C3 ◽

Postprandial Period ◽

Postprandial Triglyceride ◽

Acylation Stimulating Protein

Acylation stimulating protein (ASP), a novel adipocyte-derived autocrine protein, stimulates triglyceride synthesis and glucose transport in vitro in human and murine adipocytes. In vitro, chylomicrons increase ASP and precursor complement C3 production in adipocytes. Furthermore, in vivo, ASP production from human adipose tissue correlates positively with triglyceride clearance postprandially. The aim of the present study was to determine if intraperitoneally injected ASP accelerated triglyceride clearance in vivo after a fat load in C57Bl/6 mice. ASP increased the triglyceride clearance with a reduction of the triglyceride area under the curve over 6 h (AUC0–6) from 102.6 ± 30.0 to 61.0 ± 14.5 mg ⋅ dl−1 ⋅ h−1( P < 0.05), especially in the latter postprandial period (AUC3–6; 56.2 ± 18.0 vs. 24.9 ± 8.9 mg ⋅ dl−1 ⋅ h−1, P < 0.025). ASP also reduced plasma glucose both in the mice with accelerated plasma triglyceride clearance and in those with relatively delayed triglyceride clearance ( P < 0.025). Therefore, ASP alters postprandial triglyceride and glucose metabolism.

Download Full-text

Human adipose tissue-derived stem cells differentiate into endothelial cells in vitro and improve postnatal neovascularization in vivo

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2005.04.135 ◽

2005 ◽

Vol 332 (2) ◽

pp. 370-379 ◽

Cited By ~ 478

Author(s):

Ying Cao ◽

Zhao Sun ◽

Lianming Liao ◽

Yan Meng ◽

Qin Han ◽

...

Keyword(s):

Stem Cells ◽

Endothelial Cells ◽

Adipose Tissue ◽

Human Adipose Tissue

Download Full-text

Dopamine receptor D1- and D2-agonists do not spark brown adipose tissue thermogenesis in mice

Scientific Reports ◽

10.1038/s41598-020-77143-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Francesca-Maria Raffaelli ◽

Julia Resch ◽

Rebecca Oelkrug ◽

K. Alexander Iwen ◽

Jens Mittag

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Dopamine Receptor ◽

Ex Vivo ◽

Potential Target ◽

D2 Agonist ◽

Obesity And Diabetes ◽

Brown Adipose

AbstractBrown adipose tissue (BAT) thermogenesis is considered a potential target for treatment of obesity and diabetes. In vitro data suggest dopamine receptor signaling as a promising approach; however, the biological relevance of dopamine receptors in the direct activation of BAT thermogenesis in vivo remains unclear. We investigated BAT thermogenesis in vivo in mice using peripheral administration of D1-agonist SKF38393 or D2-agonist Sumanirole, infrared thermography, and in-depth molecular analyses of potential target tissues; and ex vivo in BAT explants to identify direct effects on key thermogenic markers. Acute in vivo treatment with the D1- or D2-agonist caused a short spike or brief decrease in BAT temperature, respectively. However, repeated daily administration did not induce lasting effects on BAT thermogenesis. Likewise, neither agonist directly affected Ucp1 or Dio2 mRNA expression in BAT explants. Taken together, the investigated agonists do not seem to exert lasting and physiologically relevant effects on BAT thermogenesis after peripheral administration, demonstrating that D1- and D2-receptors in iBAT are unlikely to constitute targets for obesity treatment via BAT activation.

Download Full-text

Glucose-Dependent Uptake of Chromium in Human and Rat Insulin-Sensitive Tissues

Clinical Science ◽

10.1042/cs0840477 ◽

1993 ◽

Vol 84 (4) ◽

pp. 477-482 ◽

Cited By ~ 12

Author(s):

Brian W. Morris ◽

Trevor A. Gray ◽

Sheila MacNeil

Keyword(s):

Adipose Tissue ◽

Human Plasma ◽

Glucose Transport ◽

Blood Cells ◽

Human Adipose Tissue ◽

Trivalent Chromium ◽

Blood Compartment

1. This study was designed to investigate the influence of insulin and glucose on the distribution of trivalent chromium in human plasma and blood cells and in human and rat insulin-sensitive and -insensitive tissues. 2. Evidence is provided that, in the rat in vitro, a clear difference exists in chromium binding between insulin-sensitive and -insensitive tissues in that chromium binding is significantly enhanced by glucose in insulin-sensitive tissues. 3. Glucose-dependent association of chromium with human adipose tissue was blocked by inhibitors of glucose transport. 4. Addition of insulin slightly increased the response to glucose in muscle and reduced the response to glucose in adipose tissue; such effects were less marked than those seen in response to glucose alone. 5. The results of this study in vitro support the hypothesis that, in vivo, chromium translocates from the blood compartment to insulin-sensitive tissues.

Download Full-text

Adipose Tissue-Derived Mesenchymal Cells Support Skin Reepithelialization through Secretion of KGF-1 and PDGF-BB: Comparison with Dermal Fibroblasts

Cell Transplantation ◽

10.3727/096368912x637064 ◽

2012 ◽

Vol 21 (11) ◽

pp. 2441-2454 ◽

Cited By ~ 17

Author(s):

Vassilia-Ismini Alexaki ◽

Despoina Simantiraki ◽

Marianna Panayiotopoulou ◽

Olga Rasouli ◽

Maria Venihaki ◽

...

Keyword(s):

Wound Healing ◽

Adipose Tissue ◽

Normal Skin ◽

Human Adipose Tissue ◽

Mesenchymal Cells ◽

Dermal Fibroblasts ◽

Skin Substitutes ◽

Keratinocyte Proliferation

Epidermal organization and homeostasis are regulated by mesenchymal influences through paracrine actions. Until today, dermal fibroblasts (DFs) are used in the “dermal” layer to support keratinocyte growth in vitro in dermal and skin substitutes. In the present work, we used human adipose tissue-derived mesenchymal cells (ADMCs) as a support of keratinocyte growth in vitro (in monolayer culture and in 3D skin cell culture models) and in vivo (mouse wound healing models) and compared our findings with those obtained using dermal fibroblasts. ADMCs induce reepithelialization during wound healing more efficiently than DFs, by enhancing keratinocyte proliferation through cell cycle progression, and migration. This effect is mediated (at least partially) by a paracrine action of KGF-1 and PDGF-BB, which are more prominently expressed in ADMCs than in DFs. Furthermore, replacement of DFs by ADMCs in the dermal compartment of organotypic skin cultures leads to an artificial epidermis resembling to that of normal skin, concerning the general histology, although with a higher expression of cytokeratins 5 and 19. In Rag1 knockout mice, ADMCs induced a more rapid reepithelialization and a more effective wound healing, compared to dermal fibroblasts. In conclusion, we provide evidence that ADMCs can serve as supportive cells for primary keratinocyte cultures. In addition, because of their abundance and the great cell yield achieved during ADMC isolation, they represent an interesting cell source, with potential aspects for clinical use.

Download Full-text

RANTES release by human adipose tissue in vivo and evidence for depot-specific differences

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90511.2008 ◽

2009 ◽

Vol 296 (6) ◽

pp. E1262-E1268 ◽

Cited By ~ 42

Author(s):

Rana Madani ◽

Kalypso Karastergiou ◽

Nicola C. Ogston ◽

Nazar Miheisi ◽

Rahul Bhome ◽

...

Keyword(s):

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Epicardial Adipose Tissue ◽

Ex Vivo ◽

Human Adipose Tissue ◽

Fat Pad ◽

Obese Subjects ◽

Subcutaneous Adipose ◽

Circulating Levels

Obesity is associated with elevated inflammatory signals from various adipose tissue depots. This study aimed to evaluate release of regulated on activation, normal T cell expressed and secreted (RANTES) by human adipose tissue in vivo and ex vivo, in reference to monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) release. Arteriovenous differences of RANTES, MCP-1, and IL-6 were studied in vivo across the abdominal subcutaneous adipose tissue in healthy Caucasian subjects with a wide range of adiposity. Systemic levels and ex vivo RANTES release were studied in abdominal subcutaneous, gastric fat pad, and omental adipose tissue from morbidly obese bariatric surgery patients and in thoracic subcutaneous and epicardial adipose tissue from cardiac surgery patients without coronary artery disease. Arteriovenous studies confirmed in vivo RANTES and IL-6 release in adipose tissue of lean and obese subjects and release of MCP-1 in obesity. However, in vivo release of MCP-1 and RANTES, but not IL-6, was lower than circulating levels. Ex vivo release of RANTES was greater from the gastric fat pad compared with omental ( P = 0.01) and subcutaneous ( P = 0.001) tissue. Epicardial adipose tissue released less RANTES than thoracic subcutaneous adipose tissue in lean ( P = 0.04) but not obese subjects. Indexes of obesity correlated with epicardial RANTES but not with systemic RANTES or its release from other depots. In conclusion, RANTES is released by human subcutaneous adipose tissue in vivo and in varying amounts by other depots ex vivo. While it appears unlikely that the adipose organ contributes significantly to circulating levels, local implications of this chemokine deserve further investigation.

Download Full-text