Understanding and recapitulating blood development for safe cell therapies
Abstract/Contents
- Abstract
- Human pluripotent stem cells (hPSCs) resemble some of the earliest cells in the developing human embryo, and they have immense potential to be used for regenerative medicine because they can differentiate into any cell type in the body. While promising, this potential is dependent on the development of better methods to differentiate hPSCs into therapeutic cell types and better tools to ensure the safety of those cells when given to patients. In this thesis, I will provide an overview of hPSC culture and differentiation, outlining many of the challenges associated with differentiating hPSCs and various strategies for overcoming these challenges. One cell type that has proven to be difficult to generate is the hematopoietic stem cell (HSC), which is of great therapeutic interest because it gives rise to all the cells that make up the blood and immune system for life, and HSCs can be used to treat or cure a variety of blood and immune diseases. Often, the most significant roadblock in differentiating a given cell type, including HSCs, is a lack of understanding in how that cell normally develops in the growing embryo. Thus, I set out to better characterize where HSCs come from by identifying the intermediate cell progenitors that give rise to HSCs during development. Applying these developmental lessons to hPSC differentiation, I developed a protocol to efficiently generate HSC-like cells that closely resemble primary HSCs. As expected, the HSC-like cells have the potential to give rise to all the major blood cell types including erythroid, myeloid, and lymphoid cells -- all of which could be utilized for regenerative medicine applications. Finally, I developed a hPSC line engineered with two orthogonal genetic safety switches to address the two primary safety risks associated with hPSC-based therapies. Ultimately, the goal of this body of work is to further advance the use of hPSCs for regenerative medicine.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Fowler, Jonas Lee |
|---|---|
| Degree supervisor | Loh, Kyle |
| Thesis advisor | Loh, Kyle |
| Thesis advisor | Majeti, Ravindra, 1972- |
| Thesis advisor | Weissman, Irving L |
| Degree committee member | Majeti, Ravindra, 1972- |
| Degree committee member | Weissman, Irving L |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Program in Stem Cell Biology & Regenerative Medicine |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Jonas Lee Fowler. |
|---|---|
| Note | Submitted to the Program in Stem Cell Biology & Regenerative Medicine. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/bm096cz8380 |
Access conditions
- Copyright
- © 2023 by Jonas Lee Fowler
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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