Cells from Patients with Ulcerative Colitis are Abnormally Inefficient

AJAS · 2022 Medicine

Ameya Saraf

Thumbnail supplied by the source for Cells from Patients with Ulcerative Colitis are Abnormally Inefficient

Overview

Ulcerative Colitis (UC) is a disease hallmarked by continuous inflammation along the gastrointestinal tract, which is largely the consequence of autoimmunity. Its prevalence continues to spread across the globe, but much of its etiology is still unknown. Current approaches to understanding the disease mechanisms of UC are limited by inaccurate models based on 2D immortalized oncogenic cell lines. To gain new insights, this study utilized colon organoids (colonoids) derived from adult stem cells (AdSCs) to analyze phenotypic variances between UC-derived colonoids and otherwise healthy colonoids. Colonoids were formed using isolated surgical samples suspended in Matrigel and were allowed to differentiate for three days. Morphology and cell differentiation were observed using area measurements and bud count respectively using digital image processing techniques. A total of ~3000 colonoid structures were measured and statistically analyzed. Conclusively, colonoids with UC had a slower growth and differentiation rate overall, suggesting intracellular abnormalities in vivo. This refined understanding of UC may result in breakthroughs in epithelial-directed treatments that enhance mucosal healing. Importantly, not only did this novel method allow for a better understanding of UC pathophysiology, but it also provided a reference for future studies involving colonoids, as current data is limited.

Video

If the video does not play, watch it on the original project page.

From the student

A few years back, I was diagnosed with Ulcerative Colitis, a lifelong autoimmune disease. Watching physicians shrug at questions surrounding my health was demoralizing, and after learning that there were millions of people like me who faced the same struggle I did, I realized I wanted to help contribute to getting our questions answered. Cincinnati Children's Hospital Medical Center was gracious enough to set me up with IBD experts Dr. Rosen and Dr. Ojo, who then helped me conduct this study. Due to COVID restrictions, the bulk of this project was conducted completely virtually, I measured all the organoids from home using a computer program known as ImageJ, and frequently talked with my mentors over Zoom. Doing this research was one of my most memorable experiences during High School, and I hope to continue pursuing biomedical research and gain more insight into Ulcerative Colitis as I grow. Thank you!

PHOTO CREDITS

Ref. 1 From Inter-observer agreement in the assessment of endoscopic findings in ulcerative colitis by Lange, Larsen 2004 BMC Gastroenterology CC BY 4.0

Ref. 3 From Selective Focus Photography of a Brown Hamster Photo by Kharawala 2015 Unsplash.

In the Public Domain

Ref. 4 From CaCo-2 cells after 21 days in culture by Aplarey 2019 Wikimedia Commons. CC BY 4.0

Ref. 5 From The Renaissance of Developmental Biology by Johnston 2015 PLOS Biology.

In the Public Domain

All pictures and tables on slides 6, 8, 9, 10 were created by the author (Ameya Saraf)

Acknowledgments

This study could not have been accomplished without the gracious support, resources, and mentorship from the Cincinnati Children’s Gastroenterology Department, in particular,

Dr. Babajide Ojo, Research Fellow at Cincinnati Children's Hospital Medical Center (Currently at the Stanford Medical Center)

Dr. Michael Rosen, Medical Director, Schubert-Martin IBD Center at Cincinnati Children's Hospital Medical Center (Currently at the Stanford Medical Center)