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Extrinsic Regulation of Intestinal S...
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Zwarycz, Bailey.
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Extrinsic Regulation of Intestinal STEM Cell Proliferation and Differentiation by Niche Components.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Extrinsic Regulation of Intestinal STEM Cell Proliferation and Differentiation by Niche Components./
作者:
Zwarycz, Bailey.
出版者:
Ann Arbor : ProQuest Dissertations & Theses, : 2018,
面頁冊數:
153 p.
附註:
Source: Dissertations Abstracts International, Volume: 79-12, Section: B.
Contained By:
Dissertations Abstracts International79-12B.
標題:
Cellular biology. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10789448
ISBN:
9780438064072
Extrinsic Regulation of Intestinal STEM Cell Proliferation and Differentiation by Niche Components.
Zwarycz, Bailey.
Extrinsic Regulation of Intestinal STEM Cell Proliferation and Differentiation by Niche Components.
- Ann Arbor : ProQuest Dissertations & Theses, 2018 - 153 p.
Source: Dissertations Abstracts International, Volume: 79-12, Section: B.
Thesis (Ph.D.)--The University of North Carolina at Chapel Hill, 2018.
This item must not be sold to any third party vendors.
The small intestinal epithelium facilitates the absorption of nutrients and provides a barrier against damaging toxins, indigestible contents, and microbes in the intestinal lumen. The epithelium is maintained by a pool of intestinal stem cells (ISCs) that reside at the base of the crypt in a supportive niche environment, made up of both cellular and non-cellular components. Niche cells, including epithelial Paneth cells, subepithelial myofibroblasts, and immune cells, along with the non-cellular extracellular matrix (ECM) provide cues that promote ISC proliferation and differentiation. The niche environment is complex and dynamic, with various cell types present that secrete different growth factors and cytokines in response to intestinal damage, inflammation, and regeneration. Extrinsic niche factors are integral for the survival and proliferation of ISCs; therefore, understanding the influence of individual niche components on ISC behavior is essential for the development of therapeutics for patient health. Here, two components of the ISC niche are investigated for their influence on ISC proliferation and differentiation: cytokines secreted from local immune cells and the underlying ECM scaffold. Through a screen of inflammatory bowel disease-related cytokines, Interleukin 22 demonstrated a concentration-dependent effect on ileal organoid size and survival in vitro. Elevated levels of Interleukin 22 limited ISC expansion in favor of increased progenitor cell differentiation and proliferation, resulting in increased organoids size and expression of antimicrobial gene products. ISC cultures rely on the use of non-intestinal based ECM components for the survival of ISCs in vitro. Using a natural, acellular intestinal scaffold provides a more physiologically relevant substrate for use both in vitro culture systems and for tissue engineering applications. By optimizing decellularization techniques, an acellular porcine small intestinal scaffold was created that retained mucosal architecture, preserved key ECM components, and supported the proliferation and differentiation of mouse small intestinal epithelium. Together, these to findings further the understanding of how extrinsic factors from the niche influence ISCs, which is of particular importance when developing therapies for intestinal disease.
ISBN: 9780438064072Subjects--Topical Terms:
3172791
Cellular biology.
Extrinsic Regulation of Intestinal STEM Cell Proliferation and Differentiation by Niche Components.
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The small intestinal epithelium facilitates the absorption of nutrients and provides a barrier against damaging toxins, indigestible contents, and microbes in the intestinal lumen. The epithelium is maintained by a pool of intestinal stem cells (ISCs) that reside at the base of the crypt in a supportive niche environment, made up of both cellular and non-cellular components. Niche cells, including epithelial Paneth cells, subepithelial myofibroblasts, and immune cells, along with the non-cellular extracellular matrix (ECM) provide cues that promote ISC proliferation and differentiation. The niche environment is complex and dynamic, with various cell types present that secrete different growth factors and cytokines in response to intestinal damage, inflammation, and regeneration. Extrinsic niche factors are integral for the survival and proliferation of ISCs; therefore, understanding the influence of individual niche components on ISC behavior is essential for the development of therapeutics for patient health. Here, two components of the ISC niche are investigated for their influence on ISC proliferation and differentiation: cytokines secreted from local immune cells and the underlying ECM scaffold. Through a screen of inflammatory bowel disease-related cytokines, Interleukin 22 demonstrated a concentration-dependent effect on ileal organoid size and survival in vitro. Elevated levels of Interleukin 22 limited ISC expansion in favor of increased progenitor cell differentiation and proliferation, resulting in increased organoids size and expression of antimicrobial gene products. ISC cultures rely on the use of non-intestinal based ECM components for the survival of ISCs in vitro. Using a natural, acellular intestinal scaffold provides a more physiologically relevant substrate for use both in vitro culture systems and for tissue engineering applications. By optimizing decellularization techniques, an acellular porcine small intestinal scaffold was created that retained mucosal architecture, preserved key ECM components, and supported the proliferation and differentiation of mouse small intestinal epithelium. Together, these to findings further the understanding of how extrinsic factors from the niche influence ISCs, which is of particular importance when developing therapies for intestinal disease.
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