Intestinal organoid/enteroid-based models for Cryptosporidium

Abstract

Cryptosporidium is a leading cause of diarrhea and death in young children and untreated AIDS patients in resource-poor settings, and of waterborne outbreaks of disease in developed countries. However, there is no consistently effective treatment for vulnerable populations. Progress towards development of therapeutics for cryptosporidiosis has been hampered by lack of optimal culture systems to study it. New advances in organoid/enteroid technology have contributed to improved platforms to culture and propagate Cryptosporidium . Here we discuss recent breakthroughs in the field and highlight different models for functional ex vivo organoid or enteroidderived culture systems. These systems will lead to a better understanding of the mechanisms of host–parasite interactions in vivo .

An update on Cryptosporidium biology and therapeutic avenues

“…In a three-dimensional matrix, HIEs spatially emulate the native host intestinal epithelium. These scaffold-based models can be used to grow Cryptosporidium and can also be used to evaluate drug efficacy and pharmacokinetics (Bhalchandra et al 2020 ; Chen et al 2017 ).…”

Cryptosporidium: Still Open Scenarios

“…Several in vitro culture systems have been reported to model Cryptosporidium infection [ 112 , 113 ]. Two-dimensional (2D) cultures of colorectal adenocarcinoma cell lines have been most frequently used, but most of these only support short term infection (<5 days) and incomplete propagation of the parasites [ 114 ].…”

Advancing animal health and disease research in the lab with three‐dimensional cell culture systems

“…However, a number of studies have now demonstrated the in vitro production of viable and infective oocysts in intestinal organoids. 35,36 These studies have tended to use human or murine organoids and therefore the use of livestock (e.g. bovine) intestinal organoids to cultivate Cryptosporidium through its life stages and for studying precise host-pathogen interactions in the main livestock host remains a key next step for veterinary parasitology research.…”

“…Prior to the implementation of intestinal organoids (or other stem cell‐derived intestinal models) as a Cryptosporidium culture platform, there was a lack of in vitro systems that facilitated the full completion of the parasite through its asexual and sexual life stages. However, a number of studies have now demonstrated the in vitro production of viable and infective oocysts in intestinal organoids 35,36 . These studies have tended to use human or murine organoids and therefore the use of livestock (e.g.…”