Using Microwells for Controlled Intestinal Differentiation of hiPS Cells

Karvelis, Elijah B.

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https://hdl.handle.net/2142/90030 Copy

Description

Title

Using Microwells for Controlled Intestinal Differentiation of hiPS Cells

Author(s)

Karvelis, Elijah B.

Contributor(s)

Griffith, Linda

Issue Date

2016

Keyword(s)

• Tissue Engineering
• Stem Cells
• Organoids
• Intestine

Abstract

Recent advancements in developmental biology and tissue engineering have greatly contributed to pharmaceuticals and drug testing by allowing for the development of more efficient and accurate in-vitro models of human tissues. In particular, the Wells lab, at the Cincinnati Childrens Hospital Medical Center, has developed a protocol for the differentiation of human induced pluripotent stem cells (hiPS cells) into intestinal organoids. However, this protocol, which mimics the in vivo microenvironment of developing definitive endoderm and mid-hindgut, often results in the random generation of gut spheroids, which later mature into organoids. The complex development of hindgut does not allow for finer analysis of the local environment pertinent to the development of an individual spheroid. To address this problem, we employed hydrogel-based microwells. By attempting to differentiate hiPS cells into mid-hindgut tissue in microwells of varying 2D dimensions, depth, and spacing, we were able to deduce more optimal conditions for the in vitro development of individual spheroids. This method will allow for improved analysis of the local factors important for spheroid generation because it reduces the previously complex culture over a relatively large surface area to the smallest-budding unit. Using this approach to gain a better understanding of the local environment may lead to an improved differentiation protocol that will result in more organized intestinal tissue useful for drug testing and disease modelling.

Type of Resource

image

Language

en

Permalink

http://hdl.handle.net/2142/90030

Sponsor(s)/Grant Number(s)

National Science Foundation under the Science and Technology Center Emergent Behaviors of Integrated Cellular Systems (EBICS).Grant Number CBET-0939511

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