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You searched for +publisher:"Georgia Tech" +contributor:("Thule, Peter"). Showing records 1 – 3 of 3 total matches.

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Georgia Tech

1. Tiernan, Aubrey Rose. Development of a pancreatic substitute based on genetically engineered intestinal endocrine cells.

Degree: PhD, Chemical and Biomolecular Engineering, 2014, Georgia Tech

Cell-based insulin therapies can potentially improve glycemic regulation in insulin dependent diabetes patients and thus help reduce secondary complications. The long-term goal of our work is to engineer autologous insulin-secreting intestinal endocrine cells as a non-beta cell approach to alleviate donor cell shortage and immune rejection issues associated with islet transplantation. These cells have been chosen for their endogenous similarity to beta cells, but generating cell constructs with sufficient insulin secretion for therapeutic effect has proven challenging. Previous work in our lab showed that a tissue engineered pancreatic substitute (TEPS) based on an engineered insulin-secreting L cell line, GLUTag-INS, was insufficient in affecting blood glucose levels in streptozotocin-induced diabetic mice, but promising since human insulin was detected in the blood. The objective of this project was therefore to fabricate an improved TEPS based on GLUTag-INS cells and evaluate its suitability as a standalone diabetes therapy. To achieve this objective, the following specific aims were (1) to investigate gene incorporation as a strategy to enhance recombinant insulin secretion from GLUTag-INS cells; (2) to develop and characterize a TEPS in vitro based on a microcapsule system containing improved GLUTag-INS cells with bioluminescence monitoring capability; and (3) to assess therapeutic efficacy of the graft in a diabetic, immune-competent mouse model and use bioluminescence monitoring to elucidate in vivo transplant behavior. This thesis therefore reports on the progression of studies from the genetic and molecular levels for improved insulin secretion per-cell, to the tissue level for enhanced secretion per-graft, and lastly to the preclinical level for therapeutic assessment in a diabetic mouse model. Advisors/Committee Members: Sambanis, Athanassios (advisor), Koros, William (committee member), Le Doux, Joe (committee member), Thule, Peter M. (committee member), Champion, Julie A. (committee member).

Subjects/Keywords: Diabetes; Bioluminescence; Intestinal L cells; Pancreatic substitute; Cell encapsulation

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APA (6th Edition):

Tiernan, A. R. (2014). Development of a pancreatic substitute based on genetically engineered intestinal endocrine cells. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/53987

Chicago Manual of Style (16th Edition):

Tiernan, Aubrey Rose. “Development of a pancreatic substitute based on genetically engineered intestinal endocrine cells.” 2014. Doctoral Dissertation, Georgia Tech. Accessed March 07, 2021. http://hdl.handle.net/1853/53987.

MLA Handbook (7th Edition):

Tiernan, Aubrey Rose. “Development of a pancreatic substitute based on genetically engineered intestinal endocrine cells.” 2014. Web. 07 Mar 2021.

Vancouver:

Tiernan AR. Development of a pancreatic substitute based on genetically engineered intestinal endocrine cells. [Internet] [Doctoral dissertation]. Georgia Tech; 2014. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/1853/53987.

Council of Science Editors:

Tiernan AR. Development of a pancreatic substitute based on genetically engineered intestinal endocrine cells. [Doctoral Dissertation]. Georgia Tech; 2014. Available from: http://hdl.handle.net/1853/53987


Georgia Tech

2. Cheng, Shing-Yi. Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells.

Degree: PhD, Chemical Engineering, 2005, Georgia Tech

Genetically engineered cells have the potential to solve the cell availability problem in developing a pancreatic tissue substitute for the treatment of insulin-dependent diabetes (IDD). These cells can be beta-cells genetically engineered so that they can be grown in culture, such as the betaTC3 and betaTC tet mouse insulinomas developed by Efrat et al; or, they can be non-beta cells genetically engineered to secrete insulin constitutively or under transcriptional regulation. The aim of this work was to thoroughly characterize and improve the secretion dynamics of pancreatic substitutes based on genetically engineered cells. One issue involved with the continuous beta-cell lines is the remodeling of the cells inside an encapsulated cell system, which may affect the insulin secretion dynamics exhibited by the construct. To evaluate the effect of remodeling on the secretion properties of the construct, we used a single-pass perfusion system to characterize the insulin secretion dynamics of different alginate beads in response to step-ups and downs in glucose concentration. Results indicated that the secretion dynamics of beads indeed changed after long-term culture. On the other hand, data with a growth-regulated cell line, betaTC tet cells, showed that the secretion profile of beads can be retained if the cell growth is suppressed. A major concern associated with genetically engineered cells of non-beta origin is that they generally exhibit sub-optimal insulin secretion characteristics relative to normal pancreatic islets. Instead of relying on molecular tools such as manipulating gene elements, our approach was to introduce a glucose-responsive material acting as a control barrier for insulin release from a device containing constitutively secreting cells. Proof-of-concept experiments were performed with a disk-shaped prototype based on recombinant HepG2 hepatomas or C2C12 myoblasts, which constitutively secreted insulin, and concanavalin A (con A)-based glucose-responsive material as the control barrier. Results demonstrated that the a hybrid pancreatic substitute consisting of constitutively secreting cells and glucose-responsive material has the potential to provide a more physiologic regulation of insulin release than the cells by themselves or in an inert material. Advisors/Committee Members: Sambanis, Athanassios (Committee Chair), Chaikof, Elliot (Committee Member), Lyon, L. Andrew (Committee Member), Thule, Peter (Committee Member), Wick, Timothy (Committee Member).

Subjects/Keywords: Pancreatic substitute; Insulin secretion dynamics; Glucose-responsive; Genetically engineered cells

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Cheng, S. (2005). Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/7160

Chicago Manual of Style (16th Edition):

Cheng, Shing-Yi. “Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells.” 2005. Doctoral Dissertation, Georgia Tech. Accessed March 07, 2021. http://hdl.handle.net/1853/7160.

MLA Handbook (7th Edition):

Cheng, Shing-Yi. “Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells.” 2005. Web. 07 Mar 2021.

Vancouver:

Cheng S. Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells. [Internet] [Doctoral dissertation]. Georgia Tech; 2005. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/1853/7160.

Council of Science Editors:

Cheng S. Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells. [Doctoral Dissertation]. Georgia Tech; 2005. Available from: http://hdl.handle.net/1853/7160


Georgia Tech

3. Bara, Heather Lynn. Tissue engineering a pancreatic substitute based on recombinant intestinal endocrine cells.

Degree: PhD, Biomedical Engineering, 2008, Georgia Tech

Cell-based treatments for insulin-dependent diabetes (IDD) may provide more physiologic regulation of blood glucose levels than daily insulin injections, thereby reducing the occurrence of secondary complication associated with IDD. An autologous cell source is especially attractive for regulatory and ethical reasons and for circumventing the need for immunosuppression, which is currently standard for islet transplantation. Our approach focuses on using adult non-β-cells engineered for physiologic insulin secretion. Specifically, we utilize enteroendocrine L-cells, which naturally exhibit regulated secretion of GLP-1 in response to physiologic stimuli, and upon genetic engineering, co-secrete insulin in a regulated manner. The overall goal of this project is to develop a tissue engineered pancreatic substitute based on a recombinant enteroendocrine cell line and test the efficacy of the pancreatic substitute by implantation into diabetic mice. The specific aims of this thesis were to (1) to modify murine L-cells for regulated insulin secretion and evaluate the insulin secretion properties of the recombinant cells; (2) to incorporate insulin-secreting L-cells into an implantable construct containing small intestinal submucosa (SIS) and to evaluate insulin secretion from the construct in vitro; and (3) to test the efficacy of the tissue engineered pancreatic substitute in vivo by implanting it intraperitoneally in mice made diabetic by streptozotocin. Thus, this proposal takes a tissue engineered pancreatic substitute for IDD from in vitro development to in vivo testing. Advisors/Committee Members: Sambanis, Athanassios (Committee Chair), Bellamkonda, Ravi (Committee Member), Garcia, Andres (Committee Member), Le Doux, Joseph (Committee Member), Thule, Peter (Committee Member).

Subjects/Keywords: GLUTag; L-cells; Tissue engineering; Diabetes; Tissue engineering; Pancreas; Insulin

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Bara, H. L. (2008). Tissue engineering a pancreatic substitute based on recombinant intestinal endocrine cells. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/26627

Chicago Manual of Style (16th Edition):

Bara, Heather Lynn. “Tissue engineering a pancreatic substitute based on recombinant intestinal endocrine cells.” 2008. Doctoral Dissertation, Georgia Tech. Accessed March 07, 2021. http://hdl.handle.net/1853/26627.

MLA Handbook (7th Edition):

Bara, Heather Lynn. “Tissue engineering a pancreatic substitute based on recombinant intestinal endocrine cells.” 2008. Web. 07 Mar 2021.

Vancouver:

Bara HL. Tissue engineering a pancreatic substitute based on recombinant intestinal endocrine cells. [Internet] [Doctoral dissertation]. Georgia Tech; 2008. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/1853/26627.

Council of Science Editors:

Bara HL. Tissue engineering a pancreatic substitute based on recombinant intestinal endocrine cells. [Doctoral Dissertation]. Georgia Tech; 2008. Available from: http://hdl.handle.net/1853/26627

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