Dissertation
A little fat never hurt anybody: how fat can influence wound healing
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Autumn 2021
DOI: 10.17077/etd.006291
Abstract
Understanding the mechanisms that influence fibroblast and myofibroblast remodeling in wound healing is imperative for development of wound healing treatment strategies. To better understand cell-cell and cell-matrix interactions in the healing process, we developed an in-vitro wound mimic with fibroblast seeded fibrin gels to help identify, quantify, and visualize fibroblast behavior and morphology in response to various different mechanical and biochemical cues. Among these biochemical cues are the secreted factors that adipocyte lineage cells produce. Adipocyte lineage cells have been investigated for their potential to contribute to the wound healing process, with different components possibly being involved in different healing stages. The details, however, of how these cells (and their secreted factors) interact with other essential cell types, such as myofibroblasts/fibroblasts, remain unclear. Using a novel in-vitro 3D human adipocyte lineage cell spheroid model, we investigated whether these adipocyte lineage cells secrete factors that affect human dermal fibroblast behavior. We isolated secreted factors from adipocyte lineage cells at different stages of differentiation, and found that not only does the secretion profile differ with maturation state, but also that fibroblasts respond differentially to adipocyte lineage cell secreted factors. This finding indicates that the secretome of adipose-derived cells changes drastically depending on differentiation state. Most notably, we found that mature adipocyte secreted factors were able to convert fibroblasts to myofibroblasts. We have also seen that adipocyte lineage cells are matrix producing, and that co-culture with fibroblasts may alter their synthetic capacity. Our findings contribute to a better understanding on the involvement of adipose tissue in wound healing, and may help to uncover and develop fat-related wound healing treatments.
Details
- Title: Subtitle
- A little fat never hurt anybody: how fat can influence wound healing
- Creators
- Mariam Yasser El-Hattab
- Contributors
- Edward A Sander (Advisor)James A. Ankrum (Committee Member)Aloysius J. Klingelhutz (Committee Member)Kristan S. Worthington (Committee Member)Suresh M.L Raghavan (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Biomedical Engineering
- Date degree season
- Autumn 2021
- DOI
- 10.17077/etd.006291
- Publisher
- University of Iowa
- Number of pages
- xii, 100 pages
- Copyright
- Copyright 2021 Mariam Yasser El-Hattab
- Language
- English
- Description illustrations
- color illustrations
- Description bibliographic
- Includes bibliographical references (pages 90-100).
- Public Abstract (ETD)
In recent years, there has been evidence showing that fat tissue and fat cells are involved actively in biological processes, such as wound healing. Surgeons have adopted the use of fat tissue grafts for various cosmetic and wound applications and have noted improvements in healing. Despite much excitement about the potential of fat tissue to reduce scarring and improve wound healing, surprisingly little is known about what the underling mechanisms involved are – especially on the cellular level.
To provide more insight on these mechanisms, our group has conducted a variety of experiments involving interactions among the different cell types within fat tissues and fibroblast skin cells, the primary driver of wound repair in healing skin. Through development of a simple wound healing mimic incorporating the use of fibroblast seeded fibrin gels, we found that secreted factors from fat cells converted dermal fibroblasts to myofibroblasts, increased their migration speed, contractile force, and collagen secretion. All of these behaviors contribute to the wound healing process and scarring.
This work is important because knowing the details of how fat cells contribute to wound healing will allow us to develop fat-related treatment strategies that have the potential to reduce scarring and fibrosis related to trauma, burns, and potentially other fibrotic diseases.
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Craniofacial Anomalies Research Center
- Record Identifier
- 9984210642502771
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