Abstract
In vitro adipose tissue models can be used to provide insight into fundamental aspects of adipose physiology. These systems may serve as replacements for animal models, which are often poor predictors of obesity and metabolic diseases in humans. Adipose tissue consists of a rich vasculature that is essential to its function. However, the study of endothelial cell–adipocyte interactions has been challenging due to differences in culture conditions required for the survival and function of each cell type. To address this issue, we performed an extensive evaluation of the cell culture media composition to identify the conditions optimal for the co-culture of endothelial cells and adipocytes. The effects of individual media factors on cell survival, proliferation, and differentiation were systematically explored. Several media factors were determined to disrupt the co-culture system. Optimized culture conditions were identified and used to generate a vascularized human adipose microtissue. An interconnected vascular network was established within an adipose micro-tissue, and the networks were anastomosed with perfused channels to form a functional network. In conclusion, media conditions were identified that enabled endothelial cell–adipocyte co-culture and were used to support the formation of a vascularized adipose tissue within a microfluidic device.
Highlights
Adipose tissue is distributed throughout the body and serves to mechanically protect organs and limbs, as well as playing a vital role in the systemic regulation of metabolism [1]
When Adipose tissue-derived stem cells (ADSCs) were pre-differentiated in 2D in the presence of IBMX prior to loading into a microfluidic chamber, the ADSCs de-differentiated into fibroblast-like cells (Figure 8), leading to fibrin deformation
IBMX was detrimental to human umbilical vein endothelial cells (HUVECs) proliferation and vessel formation, while at the same time necessary for maintaining a stable fibrin structure during human ADSC adipogenic differentiation in this study
Summary
Adipose tissue is distributed throughout the body and serves to mechanically protect organs and limbs, as well as playing a vital role in the systemic regulation of metabolism [1]. Functioning adipose tissue is a significant factor contributing to the excess morbidity and mortality observed in healthcare. Vascular remodeling may alter the nutrient and oxygen supply within adipose tissue and influence the number and size of adipocytes, playing an important role in the overall expansion of or reduction in adipose tissue volume. Adipose tissue may become hypoxic in the setting of obesity, which contributes to metabolic dysfunction [5]. The alteration of vascular function in adipose tissue could change the metabolism of the tissue, as well as endocrine and cytokine secretion [6]. Adipocytes produce proangiogenic factors and cytokines that can influence vessel remodeling [7]
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