Researchers at Boston Children’s Hospital and Brigham and Women’s Hospital have developed a lab-grown skin model with blood vessels that self-organize, respond to inflammation, and regenerate after injury, reducing reliance on animal testing.
Key Findings
- Single blood vessel cells in lab-grown skin organoids can self-organize into complex microvascular networks that grow and mature over time.
- These networks function similarly to native human skin, responding to inflammatory compounds and regenerating after injury.
- The study, published in The American Journal of Pathology, is the first to demonstrate microvascular responses to inflammatory stimuli and injury in this system.
Background
Skin organoids are small, self-organizing multicellular systems that replicate many anatomical features and biological functions of human skin. Investigators at Boston Children's Hospital developed a procedure using stem cells to generate hair-forming human skin in a dish. Researchers from Brigham and Women's Hospital used these organoids to study skin development and disease.
Details
- Vascular endothelial cells appear as early as six days into the organoid differentiation process and persist for months.
- Organoids produce molecules important for initiating and maintaining small blood vessel growth.
- As organoids grow, vessels mature and become surrounded by mural cells, similar to native skin.
- Molecular triggers of inflammation caused organoids to express proteins for immune cell homing and release inflammatory mediators.
- Organoid blood vessels regenerated after traumatic injuries.
Limitations and Future Applications
- The organoid vessels showed a molecular signature of small arteries but not veins or lymphatic vessels, indicating the system is not perfect.
- The model may be useful for studying microvasculopathy, such as in diabetes.
- Supporting NIH and FDA initiatives to create sophisticated human disease models, this work reduces reliance on animal models.
- The system allows study of pathways controlling skin blood vessel growth and function, with potential for therapeutic modulation in inflammatory skin conditions and chronic wounds.