Definition: Use of living cells or biological materials to develop therapeutic and diagnostic products that treat or prevent disease.
Examples:
Scientists use model systems to simulate human biology for study:
💡 Question on slide: “Which model systems on this line?” — invites comparing complexity and realism across these models.
Organoids are 3D multicellular structures grown from stem cells, capable of self-organization and mimicking organ function.
Key discovery: Sato et al. (Nature, 2009) – intestinal stem cells can form crypt–villus–like organoids, revolutionizing regenerative biology.
Types:
Used for:
Requires:
🧩 Components:
Two major paths:
Cells move through defined steps regulated by transcription factors and niche signals.
Stages (Day 0–4):
🧠 Matrigel acts as a “fake basement membrane” that supports 3D organization.
After several passages, organoids maintain structure and function — showing self-renewal capacity and long-term stability.
“Level-up” refers to enhancing organoid realism:
Transplantation studies show:
Brainstorm slide (“suggestions”): Possible uses include:
Brain organoids mimicking early brain development—used to model microcephaly.
Used to study viral infection pathways (e.g., SARS-CoV-2):
Shows how specific genes affect infection susceptibility.
Study findings:
Organoid grafts can restore function after intestinal injury.
Parasitic worms affecting humans/pigs — model for host–parasite interactions.
An inverted organoid structure exposing the apical surface outward, allowing:
Tuft cells: specialized intestinal cells sensing parasites. They release IL-25, activating immune cells that produce IL-13, leading to epithelial changes and anti-parasitic defense.
Goals:
IBD organoids enable personalized investigation of mucosal healing.
Organoids derived directly from IBD patients retain:
Bioengineering principles used to control shape and pattern:
Goal: reproducible, functional, and architecturally correct organoids.
Cells self-organize into defined epithelial zones guided by:
YAP1 (mechanosensor protein) determines if cells proliferate or differentiate:
Combining stem cells with:
Leads to organoids with improved reproducibility and function.
Innovative engineering approaches producing customized mini-organs with defined shape and function (e.g., gut-on-chip, brain chips).
ImageJ used for:
Prompt for reflection:
Mimic human brain development and function in 3D. Used to study:
Patient-derived tumor organoids allow:
Show early brain patterning, neural tube-like regions, and cortical organization.
hiPSCs → embryoid bodies → neural induction → cortical tissue layers. Recapitulates early neurogenesis.
Challenges:
Quantitative imaging shows growth variability; standardization needed for reproducible results.
Two brain organoids connected via microelectrode array (MEA) → record neuronal communication and network activity — “mini-brains” interacting!
Connected organoids show spontaneous electrical signaling, similar to neural circuits — foundation for studying learning-like processes in vitro.
Formation of axon tracts linking two organoids — showing real synaptic connectivity between separate “brain islands.”
Used GelMA hydrogels and unidirectional scaffolds for guided neural outgrowth between organoids. Stained for:
Demonstrates engineered connectivity in vitro.
| Concept | Key Idea |
|---|---|
| Organoids | 3D self-organizing stem cell–derived mini-organs |
| Applications | Disease modeling, drug screening, regenerative therapy |
| Engineering advances | Controlled shape, bioengineered scaffolds, vascularization |
| Ethical issues | Especially relevant for brain organoids |
| Future outlook | Towards functional, connected, and patient-specific organoid systems |