Jaramillo, Maria
(2013)
Recapitulating Pancreatic Development in Inducing In-Vitro Human Embryonic Stem Cell Differentiation.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Differentiation of human pluripotent stem cells into pancreatic beta cells could lead to the development of clinically relevant cells for the treatment of pathologies of the pancreas, specifically type 1 diabetes, which is the most common reason for pancreatic transplantation. Type 1 diabetes is a disease that consists in damage of insulin producing β-cells, therefore impaired regulation of blood glucose levels. While a number of groups have reported generation of differentiated phenotypes from stem cells expressing Insulin, all of these protocols have been limited by low yield and lack of mature functional cell types.
Organogenesis is a complex and dynamic process regulated by a milieu of chemical and physical signals along with interaction with neighboring cell types, all of which constitute the microenvironmental niche of a developing organ. It is well recognized that in-vitro differentiation of embryonic stem cells can be best achieved by closely recapitulating the in-vivo micro-environmental niche. However, such an effort towards concerted modulation of different micro-environmental components is largely lacking in the area of pancreatic differentiation, where the primary focus till date have been on soluble chemical cues. We hypothesize that modulation of the chemical and physical micro-environment along with adequate intra-cellular signaling can effectively modulate the functionality and fate commitment of differentiating population of stem cells. In order to test this hypothesis we developed strategies to alter physical properties ofv
substrates, modify soluble signals during early stages of differentiation and use of novel intracellular signaling in pancreatic islet maturation.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
25 September 2013 |
| Date Type: |
Publication |
| Defense Date: |
27 June 2013 |
| Approval Date: |
25 September 2013 |
| Submission Date: |
25 July 2013 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
131 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Bioengineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Embryonic stem cells, Differentiation,
pancreas, Insulin, Beta cells |
| Date Deposited: |
25 Sep 2013 12:50 |
| Last Modified: |
15 Nov 2016 14:14 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/19445 |
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