Characterization and modeling of cell activation upon TGF-β1 stimulation in a 3-D culture system

Xu, Jing

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https://hdl.handle.net/2142/16963 Copy

Description

Title

Characterization and modeling of cell activation upon TGF-β1 stimulation in a 3-D culture system

Author(s)

Xu, Jing

Issue Date

2010-08-31T20:02:23Z

Director of Research (if dissertation) or Advisor (if thesis)

Insana, Michael F.

Department of Study

Bioengineering

Discipline

Bioengineering

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

M.S.

Degree Level

Thesis

Keyword(s)

• myofibroblasts
• transforming growth factor-beta1
• alpha-smooth muscle actin
• diffusion
• confocal microscopy imaging
• immunofluorescence staining

Abstract

In this work, we explored a thick in vitro 3-D cell culture model with layered structure and applied transforming growth factor-beta1 (TGF-β1) on the top of the 3-D culture to induce the conversion from normal fibroblasts to myofibroblasts and expression of a marker protein, alpha-smooth muscle actin (α-SMA). The cell response with TGF-β1 stimulation was captured with immunofluorescence staining (IF) and confocal microscopy imaging of α-SMA in each cell embedded layer. Our results revealed the spatial-temporal profiles of the conversion from normal fibroblasts to myofibroblasts in 3-D culture upon TGF-β1stimulation. The conversion starting time, speed and saturation plateau are closely related to TGF-β1 concentration. Based on these experimental results, we successfully developed a mathematical model, which incorporates diffusion of growth factors and cell activation responses to describe the dynamic cell response to growth factors across the 3-D culture depth and predict the spatial-temporal profile of the fibroblast conversion within the culture. In summary, we present here a handy experimental and computational tool for researches on tumor signaling pathways, and provide some guidance for studies on diffusion of protein factors or drugs in 3-D tissue environment.

Graduation Semester

2010-08

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http://hdl.handle.net/2142/16963

Copyright and License Information

Copyright 2010 Jing Xu

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