東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Investigating the Differentiation an...

Velazco-Cruz, Leonardo.

FindBook

Google Book

Amazon

博客來

Investigating the Differentiation and Functional Maturation of Stem Cell-Derived β Cells.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Investigating the Differentiation and Functional Maturation of Stem Cell-Derived β Cells./
作者:	Velazco-Cruz, Leonardo.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:	229 p.
附註:	Source: Dissertations Abstracts International, Volume: 83-03, Section: B.
Contained By:	Dissertations Abstracts International83-03B.
標題:	Biology. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28719263
ISBN:	9798538113736

Investigating the Differentiation and Functional Maturation of Stem Cell-Derived β Cells.
Velazco-Cruz, Leonardo.

Investigating the Differentiation and Functional Maturation of Stem Cell-Derived β Cells. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 229 p.

Source: Dissertations Abstracts International, Volume: 83-03, Section: B.

Thesis (Ph.D.)--Washington University in St. Louis, 2021.

This item must not be sold to any third party vendors.

Diabetes mellitus is a chronic and global disease rapidly growing in prevalence. Diabetes can be characterized by the dysfunction or death of the glucose sensing insulin secreting β cell. β cells are located within the islet of Langerhans (islet), a tissue within the pancreas. Human islets are critical for the study and treatment of diabetes. However, they can only be obtained from cadaveric organ donors. These cadaveric islets do not proliferate and can only be maintained in vitro for short periods of time, making their availability rare and fleeting. Stem cell-derived β-like cells can be generated in indefinite amounts and are a potential alternative to cadaveric islet cells. Throughout this document stem cell-derived β-like cells will be interchangeably referred as SC-β cells or SC-islet. A major challenge towards applying SC-β cells to disease modeling or cell replacement therapies is their lack of functional maturity and supporting technology. In this thesis, I am to investigate and improve the functional maturity of SC-β cells and their supporting technologies. Chapter 1 serves as an introduction to the field of SC-β cells. In Chapter 2, by temporally manipulating TGFβ signaling, I develop a novel differentiation protocol for generation of SC-β cells with enhance function. These enhanced SC-β cells are generated more efficiently and achieve dynamic insulin secretion with first and second phase insulin secretion kinetics, a critical hallmark of cadaveric islet function. When transplanted into immune compromised diabetic mice, their function is detected within two weeks and cure their diabetes. In Chapter 3, I elucidate the role of transcription factor SIX2 in SC-β cells differentiations. Using gene knockdown and knockout techniques, I show SIX2's necessity for the functional maturation of SC-β cells. Importantly, I identify SIX2 positive and negative β cell populations and postulate its use as a marker to guide future β cell maturation efforts. In Chapter 4, I present a method for cryopreserving SC-islets and characterize them relative to their un-cryopreserved counterparts. Cryopreserved SC-islets functionally and transcriptionally resemble un-cryopreserved SC-islets. This advancement will facilitate biobanking of stem cells, a necessary step to increase their accessibility to the research and therapeutic research population. In Appendix A, I describe the application of a luciferase insulin secretion reporter in SC-β cells. Luciferase co-secretes in correlation with insulin and a proof-of-concept compound screen is performed identifying several β cell secretagogues. These secretagogues were then assessed with cadaveric islets verifying the potential of SC-β cells as biologically relevant screening models. In Appendix B, I describe a method for co-culturing SC-β cells with endothelial cells using a hydrogel system. The work in this thesis advances SC-β cell technologies and facilitates their use as disease models and cell-therapeutics.

ISBN: 9798538113736Subjects--Topical Terms:

522710
Biology.
Subjects--Index Terms:

Beta

Investigating the Differentiation and Functional Maturation of Stem Cell-Derived β Cells.
LDR:04158nmm a2200373 4500 001 2283668
005 20211115071527.5
008 220723s2021 ||||||||||||||||| ||eng d
020 $a 9798538113736
035 $a (MiAaPQ)AAI28719263
035 $a AAI28719263
040 $a MiAaPQ $c MiAaPQ
100 1 $a Velazco-Cruz, Leonardo. $0 (orcid)0000-0003-4664-3936 $3 3562681
245 1 0 $a Investigating the Differentiation and Functional Maturation of Stem Cell-Derived β Cells.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2021
300 $a 229 p.
500 $a Source: Dissertations Abstracts International, Volume: 83-03, Section: B.
500 $a Advisor: Millman, Jeffrey.
502 $a Thesis (Ph.D.)--Washington University in St. Louis, 2021.
506 $a This item must not be sold to any third party vendors.
520 $a Diabetes mellitus is a chronic and global disease rapidly growing in prevalence. Diabetes can be characterized by the dysfunction or death of the glucose sensing insulin secreting β cell. β cells are located within the islet of Langerhans (islet), a tissue within the pancreas. Human islets are critical for the study and treatment of diabetes. However, they can only be obtained from cadaveric organ donors. These cadaveric islets do not proliferate and can only be maintained in vitro for short periods of time, making their availability rare and fleeting. Stem cell-derived β-like cells can be generated in indefinite amounts and are a potential alternative to cadaveric islet cells. Throughout this document stem cell-derived β-like cells will be interchangeably referred as SC-β cells or SC-islet. A major challenge towards applying SC-β cells to disease modeling or cell replacement therapies is their lack of functional maturity and supporting technology. In this thesis, I am to investigate and improve the functional maturity of SC-β cells and their supporting technologies. Chapter 1 serves as an introduction to the field of SC-β cells. In Chapter 2, by temporally manipulating TGFβ signaling, I develop a novel differentiation protocol for generation of SC-β cells with enhance function. These enhanced SC-β cells are generated more efficiently and achieve dynamic insulin secretion with first and second phase insulin secretion kinetics, a critical hallmark of cadaveric islet function. When transplanted into immune compromised diabetic mice, their function is detected within two weeks and cure their diabetes. In Chapter 3, I elucidate the role of transcription factor SIX2 in SC-β cells differentiations. Using gene knockdown and knockout techniques, I show SIX2's necessity for the functional maturation of SC-β cells. Importantly, I identify SIX2 positive and negative β cell populations and postulate its use as a marker to guide future β cell maturation efforts. In Chapter 4, I present a method for cryopreserving SC-islets and characterize them relative to their un-cryopreserved counterparts. Cryopreserved SC-islets functionally and transcriptionally resemble un-cryopreserved SC-islets. This advancement will facilitate biobanking of stem cells, a necessary step to increase their accessibility to the research and therapeutic research population. In Appendix A, I describe the application of a luciferase insulin secretion reporter in SC-β cells. Luciferase co-secretes in correlation with insulin and a proof-of-concept compound screen is performed identifying several β cell secretagogues. These secretagogues were then assessed with cadaveric islets verifying the potential of SC-β cells as biologically relevant screening models. In Appendix B, I describe a method for co-culturing SC-β cells with endothelial cells using a hydrogel system. The work in this thesis advances SC-β cell technologies and facilitates their use as disease models and cell-therapeutics.
590 $a School code: 0252.
650 4 $a Biology. $3 522710
650 4 $a Research. $3 531893
650 4 $a Population. $3 518693
650 4 $a Diabetes. $3 544344
650 4 $a Glycoproteins. $3 667972
650 4 $a Transplants & implants. $3 3562683
650 4 $a Mutation. $3 837917
650 4 $a Metabolism. $3 541349
650 4 $a Insulin. $3 3206757
650 4 $a Genomics. $3 600531
650 4 $a Peptides. $3 605772
650 4 $a Respiration. $3 610890
650 4 $a Kinases. $3 3558077
650 4 $a Efficiency. $3 753744
650 4 $a Growth factors. $3 657607
650 4 $a Gene expression. $3 643979
650 4 $a Pancreas. $3 1244724
650 4 $a Endocrinology. $3 610914
650 4 $a Genetic engineering. $3 530509
650 4 $a Glucose. $3 2084335
650 4 $a Biotechnology. $3 571461
650 4 $a Stem cells. $3 767761
650 4 $a Hydrogels. $3 1305894
650 4 $a Transcription factors. $3 669191
650 4 $a Nutrition. $3 517777
653 $a Beta
653 $a Diabetes
653 $a Insulin
653 $a Islet
653 $a Stem cell
690 $a 0306
690 $a 0409
690 $a 0570
710 2 $a Washington University in St. Louis. $b Biology & Biomedical Sciences (Developmental, Regenerative, & Stem Cell Biology). $3 3562682
773 0 $t Dissertations Abstracts International $g 83-03B.
790 $a 0252
791 $a Ph.D.
792 $a 2021
793 $a English
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28719263