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Guided Organogenesis Using Mosaic Patterns of Progenitors Catherine M Porter
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Porter, Catherine M., author.
- Language:
- English
- Subjects (All):
- Bioengineering.
- Biomedical engineering.
- Developmental biology.
- Cellular biology.
- Morphology.
- 0202.
- 0541.
- 0758.
- 0379.
- 0287.
- Local Subjects:
- Bioengineering.
- Biomedical engineering.
- Developmental biology.
- Cellular biology.
- Morphology.
- 0202.
- 0541.
- 0758.
- 0379.
- 0287.
- Physical Description:
- 1 electronic resource (154 pages)
- Contained In:
- Dissertations Abstracts International 86-07B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2024
- Language Note:
- English
- Summary:
- Organoids derived from human stem cells are a promising approach for disease modeling, regenerative medicine, and fundamental research. However, organoid variability and limited control over morphological outcomes remain as challenges. Engineering control over culture conditions may guide organoids toward specific outcomes in self-organization, including tissue composition and architecture. Here, we extend DNA-Programmed Assembly of Cells (DPAC), a DNA 'velcro' cell patterning approach. We first modify DPAC to a photolithographic method (pDPAC) that expands DNA patterning from the millimeter- to the centimeter-scale. We then apply pDPAC to build self-folding constructs of co-patterned cells on extracellular (ECM) matrix protein sheets, termed kinomorphs. We show that rationally designed configurations of 3T3 fibroblasts apply traction forces, which actuate prescribed folding of ECM sheets. In turn, ECM compaction guides the coalescence and tubulogenesis of adjacent, patterned epithelial Madin-Darby canine kidney cells along crease patterns that partially mimic the branched ureteric epithelium of the kidney. Kinomorphs and other large-scale pDPAC applications may significantly advance organ-scale tissue construction by extending the spatial range of cell self-organization in emerging model systems such as organoids. In a second study, we use pDPAC to precisely control the number and ratio of human induced pluripotent stem cell-derived progenitors contributing to nephron progenitor (NP) organoids and mosaic NP/ureteric bud (UB) tip cell organoids within arrays of microwells. We demonstrate long-term control over organoid size and morphology, decoupled from geometric constraints. We then show emergent trends in organoid tissue proportions and organization that depend on initial progenitor cell composition. Our findings verify the utility of pDPAC in guiding organotypic self-organization. Finally, we consider our research's current limitations and future directions, beginning to explore how 2D patterns of kidney progenitors may transition to 3D geometries of higher physiologic relevance. Our cell patterning approach shows great potential as a blueprinting strategy to one day build complex, customizable, and fully functional tissues and organs. Alleviating substantial health and financial burdens, our work could help pave the way to revolutionized healthcare where access to a lifesaving organ transplant is no longer a waiting game
- Notes:
- Source: Dissertations Abstracts International, Volume: 86-07, Section: B.
- Advisors: Hughes, Alex J. Committee members: Issadore, David A.; Good, Matthew C.; Lengner, Christopher J.
- Ph.D. University of Pennsylvania 2024
- Local Notes:
- School code: 0175
- ISBN:
- 9798302183507
- Access Restriction:
- Restricted for use by site license
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