Long-Term Severe In Vitro Hypoxia Exposure Enhances the Vascularization Potential of Human Adipose Tissue-Derived Stromal Vascular Fraction Cell Engineered Tissues

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.

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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

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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.

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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

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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.

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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

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The In Vivo Evaluation of the Therapeutic Potential of Human Adipose Tissue-Derived Mesenchymal Stem Cells for Acute Liver Disease

Methods in Molecular Biology - Animal Models for Stem Cell Therapy ◽

10.1007/978-1-4939-1453-1_6 ◽

2014 ◽

pp. 57-67 ◽

Cited By ~ 6

Author(s):

Takeshi Katsuda ◽

Hayato Kurata ◽

Rie Tamai ◽

Agnieszka Banas ◽

Tsuyoshi Ishii ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Liver Disease ◽

Therapeutic Potential ◽

Human Adipose Tissue ◽

In Vivo Evaluation ◽

Acute Liver Disease

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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.

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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.

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Estrogen Controls Lipolysis by Up-Regulating α2A-Adrenergic Receptors Directly in Human Adipose Tissue through the Estrogen Receptor α. Implications for the Female Fat Distribution

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2003-031327 ◽

2004 ◽

Vol 89 (4) ◽

pp. 1869-1878 ◽

Cited By ~ 143

Author(s):

Steen B. Pedersen ◽

Kurt Kristensen ◽

Pernille A. Hermann ◽

John A. Katzenellenbogen ◽

Bjørn Richelsen

Keyword(s):

Estrogen Receptor ◽

Adipose Tissue ◽

Adrenergic Receptors ◽

Human Adipose Tissue ◽

Fat Distribution ◽

Receptor Subtype ◽

Fat Depots ◽

Fat Depot

Abstract Estrogen seems to promote and maintain the typical female type of fat distribution that is characterized by accumulation of adipose tissue, especially in the sc fat depot, with only modest accumulation of adipose tissue intraabdominally. However, it is completely unknown how estrogen controls the fat accumulation. We studied the effects of estradiol in vivo and in vitro on human adipose tissue metabolism and found that estradiol directly increases the number of antilipolytic α2A-adrenergic receptors in sc adipocytes. The increased number of α2A-adrenergic receptors caused an attenuated lipolytic response of epinephrine in sc adipocytes; in contrast, no effect of estrogen on α2A-adrenergic receptor mRNA expression was observed in adipocytes from the intraabdominal fat depot. These findings show that estrogen lowers the lipolytic response in sc fat depot by increasing the number of antilipolytic α2A-adrenergic receptors, whereas estrogen seems not to affect lipolysis in adipocytes from the intraabdominal fat depot. Using estrogen receptor subtype-specific ligands, we found that this effect of estrogen was caused through the estrogen receptor subtype α. These findings demonstrate that estrogen attenuates the lipolytic response through up-regulation of the number of antilipolytic α2A-adrenergic receptors only in sc and not in visceral fat depots. Thus, our findings offer an explanation how estrogen maintains the typical female sc fat distribution because estrogen seems to inhibit lipolysis only in sc depots and thereby shifts the assimilation of fat from intraabdominal depots to sc depots.

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