Intestinal Organoids

Overview

Intestinal organoids are 3D miniaturized and self-organizing tissue cultures derived from intestinal stem cells. They replicate key features of the native gut epithelium—including cellular composition, polarity, and function—making them a transformative tool for studying human intestinal biology in vitro. These structures can be derived from: Adult intestinal stem cells (ASCs) harvested from biopsies Pluripotent stem cells (PSCs) such as embryonic stem cells or induced pluripotent stem cells (iPSCs) Depending on the source, organoids can model fetal development, adult tissue homeostasis, or disease states, offering insights across a broad biological and clinical spectrum.

                   Intestinal crypt isolation at the single cell level and crypt level

Key Features

Self-organization: Driven by intrinsic signaling, organoids develop crypt-villus architecture and regional identity.

Cellular diversity: Include absorptive enterocytes, goblet cells, Paneth cells, enteroendocrine cells, tuft cells, and stem/progenitor populations.

Long-term culture: Can be expanded and passaged over months while retaining key phenotypes.

Personalized models: Enable patient-specific studies, such as precision medicine for IBD or cystic fibrosis.

Manipulable system: Compatible with CRISPR gene editing, co-culture, microfluidics, and imaging.Key Features

 

Organoid growth in increasing order at crypt level. All organoids were grown in Conditional medium.
Organoid growth in increasing order at crypt level. All organoids were grown in Differential medium.

Applications

🧬 Developmental Biology

Organoids derived from different post-conception weeks (e.g., 9, 12, 22 weeks) recapitulate fetal gut maturation, providing a human-specific model to study:

  • Epithelial differentiation

  • Tissue patterning

  • Barrier formation

  • Early onset diseases like necrotizing enterocolitis (NEC)

🔬 Disease Modeling

Organoids enable the study of diseases in a patient-specific context:

  • Inflammatory Bowel Disease (IBD)

  • Colorectal cancer

  • Cystic fibrosis

  • Infectious diseases (e.g., rotavirus, SARS-CoV-2)

💊 Drug Screening

High-throughput assays using organoids provide a platform to:

  • Test epithelial responses to drugs or toxins

  • Screen CFTR-modulating therapies

  • Model nutrient absorption and metabolism

🦠 Host-Microbe Interactions

Co-culture systems with bacteria or immune cells allow interrogation of how the intestinal barrier responds to:

  • Pathogenic microbes

  • Commensal bacteria

  • Inflammatory stimuli

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Technical Capabilities in Our Lab

Our lab uses:

  • Fetal- and adult-derived organoids

  • Live-cell imaging and super-resolution microscopy (e.g., STED)

  • Functional assays: TEER, permeability, and cytokine profiling

  • CRISPR/Cas9 genome editing

  • Organoid-on-chip systems to mimic flow and mechanical cues