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Inflammation induced changes in adipocytes
Title
Inflammation induced changes in adipocytes
Creator
Kim, Kihwan
Date
2019
Description
The significant features of Crohn’s Disease include creeping fat that covers more than 50% of both small and large intestine surfaces and high...
Show moreThe significant features of Crohn’s Disease include creeping fat that covers more than 50% of both small and large intestine surfaces and high level of inflammatory cytokines such as TNF-alpha and IL-6. However, the relationship between these two factors of Crohn’s Disease is still unknown. Therefore, verifying the relationship could contribute to understanding the cause of Crohn’s Disease. In this study, preadipocytes were used because they have a potential to grow as adipocytes which are developed as creeping fat. The objective of this study was to observe proliferation, differentiation, and chemotaxis of preadipocytes in inflammatory microenvironment. It was found that only TNF-alpha stimulates preadipocyte proliferation whereas IL-6 does not. However, both TNF-alpha and IL-6 inhibit differentiation of preadipocytes. Furthermore, preadipocytes did not have chemotactic responses towards both cytokines. Therefore this study concludes that these inflammatory microenvironments induce the preadipocytes proliferation in Crohn’s. However, they inhibit adipogenesis and recruitment of the preadipocytes in Crohn’s.
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ENGINEERING HUMAN ADIPOSE TISSUE WITHIN A MICROFLUIDIC DEVICE
Title
ENGINEERING HUMAN ADIPOSE TISSUE WITHIN A MICROFLUIDIC DEVICE
Creator
Yang, Feipeng
Date
2019
Description
Adipose tissue models can be used for in vitro drug screening of therapeutics designed for the treatment of obesity or adipose tissue-related...
Show moreAdipose tissue models can be used for in vitro drug screening of therapeutics designed for the treatment of obesity or adipose tissue-related diseases. This work aimed to engineer functional three-dimensional (3D) adipose microtissue models that could be incorporated within a microfluidic system. To support the on-chip 3D culture, a microfluidic device consisted of cell culture chambers flanked by two side channels was designed. The mold for the microfluidic device was manufactured using computer numeric control (CNC) micro-milling. Soft lithography with polydimethylsiloxane (PDMS) was used to construct the microchannels and chambers in the microfluidic device. A model was developed by the monoculture of adipocytes within the microfluidic device. Human adipose-derived stem cells (ADSCs) were differentiated toward adipocyte in the cell culture chambers and formed a 3D adipose microtissue. The effect of interstitial flow on the adipogenic differentiation of ADSCs was explored. Adipocytes showed decreased adiponectin secretion and increased lipolysis in response to increased interstitial shear stress. Meanwhile, multiple adipogenic genes were downregulated with the increase in shear stress.To engineer vascularized adipose tissue, a co-culture system with ADSCs, human umbilical vein endothelial cells (HUVECs) and normal human lung fibroblasts (NHLFs) was applied. Culture conditions (media, cell ratios, temporal conditions, etc.) for optimal differentiation of ADSCs and induction of network formation were identified. ADSCs were induced toward adipogenesis before mixed with HUVECs and NHLFs. The cell mixture was loaded into the microfluidic device and formed an adipose microtissue with a vessel network in a mixed culture media. An interconnected vascular network was established within 2 weeks and formed anastomoses with the side channels. Perfusion of fluorescent dextran confirmed the interconnections and lumen formation of the vascular network. Perfusion of fluorescently labeled fatty acid analog through vessels resulted in the accumulation of the fatty acid in adipocytes, confirming the functionality of the adipose microtissue. In conclusion, this work presented adipose tissue models within a microfluidic device that can potentially be utilized for on-chip drug screening, as well as provide insights into the engineering of complex tissues.
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