# Bioengineered 3D primary human intestinal model for Cryptosporidium

> **NIH NIH U19** · TUFTS UNIVERSITY BOSTON · 2020 · $21,880

## Abstract

The intestinal Apicomplexan parasite Cryptosporidium (Crypto) is a leading cause of diarrhea and
death in malnourished young children and untreated HIV/AIDS patients in the resource-constrained world and
a major cause of waterborne outbreaks in developed countries Despite the global burden of Crypto, treatment
options for cryptosporidiosis are severely limited. There are several constraints to drug development for
cryptosporidiosis. The host parasite interactions that mediate pathogenesis and the pathways and molecules
that can be targeted for drug development are poorly understood. The lack of a primary human intestinal model
that recapitulates human intestinal structure and function and supports continuous infection of wild type and
transgenic Crypto is a major limitation to understanding pathogenesis and pre-clinical screening for anti-
cryptosporidial interventions.
 We recently developed a bioengineered 3D primary human intestinal model in vitro using silk protein
scaffolds seeded with human IEC lines and myofibroblasts. This model supported continuous C. parvum
infection for at least 15 days and C. parvum from infected scaffolds could re-infect new scaffolds for up to three
cycles. However, since IEC lines may not recapitulate normal human IEC structure and function, we
incorporated human ileal enteroids (instead of IEC lines) into the system. Our preliminary data indicate that
enteroids incorporated into this model which supports robust C. parvum infection.
 The overall goal of this project is to investigate host-parasite interactions of human Crypto infection and
develop drug screening for cryptosporidiosis using 3D human ileal enteroid-based models under flow,
peristaltic and low oxygen conditions. Our central hypothesis is that this model is a breakthrough technological
advance that will expedite investigation of human Crypto infection and facilitate pre-clinical testing of
interventions for cryptosporidiosis.
 The Specific Aims are to: 1) elucidate host-parasite interactions in Crypto infection in bioengineered
primary 3D human enteroid-based tissue model under peristaltic, flow and low oxygen conditions in a
bioreactor system and 2) evaluate an integrated 3D primary human enteroid-based “mini-gut” model under the
same conditions for selected host-parasite interactions and as a pre-clinical model of cryptosporidiosis for
screening of drugs and probiotics.
 Success in establishing 3D, enteroid-based human intestinal tissue models and achieving continuous
propagation of infection will be transformative for Crypto research. The model can be used to study host-
parasite-microbe interactions and test targeted interventions for cryptosporidiosis.

## Key facts

- **NIH application ID:** 10071564
- **Project number:** 3U19AI131126-03S1
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Honorine D Ward
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $21,880
- **Award type:** 3
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071564

## Citation

> US National Institutes of Health, RePORTER application 10071564, Bioengineered 3D primary human intestinal model for Cryptosporidium (3U19AI131126-03S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10071564. Licensed CC0.

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