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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Adriana Mulero-Russe
BioE Ph.D. Proposal Presentation
December 15, 2021
1:00PM
1128 IBB and BlueJeans Link: https://bluejeans.com/260554335/3619
Meeting ID: 260 554 335
Advisor:
Andrés García, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology
Committee Members:
Michael A. Helmrath, M.D., Division of Pediatric General and Thoracic Surgery, Cincinnati Children’s Hospital Medical Center
Hang Lu, Ph.D. School of Chemical & Biomolecular Engineering, Georgia Institute of Technology
Asma Nusrat, M.D., Department of Pathology University of Michigan
Johnna S. Temenoff, Ph.D., School of Biomedical Engineering Georgia Institute of Technology
Engineered Synthetic Platform for Human Intestinal Organoid Generation and Delivery
Human intestinal organoids (HIOs) are three-dimensional (3D) multicellular structures, derived from either adult intestinal stem cells or human pluripotent stem cells (hPSCs), that recapitulate human intestinal tissue architecture. HIOs are a promising cell source for intestinal tissue repair, disease modeling, and drug screening. Previous work has demonstrated that HIOs engraft to the injured intestinal wall in vivo, however, these approaches are significantly limited by the lack of an appropriate delivery vehicle to drive HIO engraftment. HIO generation from hPSCs is a multi-stage directed differentiation process comprising three stages: (I) a definitive endoderm 2D monolayer, (II) self-organized 3D aggregates (human intestinal spheroids, HIS), and (III) intestinal specification into HIOs within a 3D extracellular matrix. This in vitro culture process spans a 2D growth substrate (stage I and II) to a 3D matrix (stage III). The growth stages (2D and 3D) are supported by Matrigel, a murine tumor-derived basement membrane extract with ill-defined composition, lot-to-lot variability, and limited clinical translation potential presenting a major roadblock to HIOs clinical translation. Another roadblock to HIO technologies is the low yield and consistency of HIS differentiation in HIOs. The objectives of this project are to (1) engineer a synthetic hydrogel platform with independent control of the biochemical and biophysical cues guiding the entire in vitro differentiation of hPSCs into HIOs, and (2) deliver HIOs in a synthetic coating to intestinal injuries in vivo. The central hypothesis of this work is that engineering a PEG-based synthetic matrix to support HIO in vitro generation and in vivo delivery will increase the reproducibility, yield, and clinical translatability of this transformative organoid technology.
