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Updated: Mar 9, 2026
Author Spotlight: Investigating the Effects of Compounds on Intestinal Tissue Using 3D Human Cell Line Models
Published on: September 1, 2023
Novel Bioengineered Three-Dimensional Human Intestinal Model for Long-Term Infection of Cryptosporidium parvum
Maria A DeCicco RePass1,2, Ying Chen3, Yinan Lin3
1Tufts University Sackler School of Graduate Biomedical Sciences, Boston, Massachusetts, USA.
Abstract:
Cryptosporidium spp. are apicomplexan parasites of global importance that cause human diarrheal disease. In vitro culture models that may be used to study this parasite and that have physiological relevance to in vivo infection remain suboptimal. Thus, the pathogenesis of cryptosporidiosis remains poorly characterized, and interventions for the disease are limited. In this study, we evaluated the potential of a novel bioengineered three-dimensional (3D) human intestinal tissue model (which we developed previously) to support long-term infection by Cryptosporidium parvum Infection was assessed by immunofluorescence assays and confocal and scanning electron microscopy and quantified by quantitative reverse transcription-PCR. We found that C. parvum infected and developed in this tissue model for at least 17 days, the extent of the study time used in the present study. Contents from infected scaffolds could be transferred to fresh scaffolds to establish new infections for at least three rounds. Asexual and sexual stages and the formation of new oocysts were observed during the course of infection. Additionally, we observed ablation, blunting, or distortion of microvilli in infected epithelial cells. Ultimately, a 3D model system capable of supporting continuous Cryptosporidium infection will be a useful tool for the study of host-parasite interactions, identification of putative drug targets, screening of potential interventions, and propagation of genetically modified parasites.
Insights
A novel 3D human intestinal model supports long-term Cryptosporidium parvum infection, enabling detailed study of cryptosporidiosis. This breakthrough advances research into parasite-host interactions and potential treatments.
Area of Science:
- Parasitology
- Microbiology
- Bioengineering
Background:
- Cryptosporidium spp. are significant human pathogens causing diarrheal disease.
- Current in vitro models for studying Cryptosporidium lack physiological relevance, hindering research into pathogenesis and treatment.
- Understanding host-parasite interactions is crucial for developing effective interventions.
Purpose of the Study:
- To evaluate a novel bioengineered 3D human intestinal tissue model for supporting long-term Cryptosporidium parvum infection.
- To characterize the parasite's development and host cell interactions within this advanced in vitro system.
- To establish a reliable model for studying cryptosporidiosis and screening potential therapies.
Main Methods:
- Utilized a previously developed bioengineered 3D human intestinal tissue model.
- Infected the model with Cryptosporidium parvum and assessed infection via immunofluorescence assays, confocal and scanning electron microscopy.
- Quantified parasite load using quantitative reverse transcription-PCR and evaluated serial infections between scaffolds.
Main Results:
- The 3D model supported sustained Cryptosporidium parvum infection for at least 17 days.
- Infections could be serially transferred to new scaffolds for at least three rounds.
- Asexual and sexual parasite stages, oocyst formation, and microvilli damage were observed.
- The model demonstrated physiological relevance to in vivo infection.
Conclusions:
- The developed 3D human intestinal model is a robust platform for long-term Cryptosporidium infection.
- This model facilitates the study of host-parasite interactions and parasite development.
- It serves as a valuable tool for identifying drug targets, screening interventions, and propagating parasites.
