Free-floating long-term vascularized mesenchymal organoids.

Area of Science:

• Biomedical Engineering
• Stem Cell Biology
• Cancer Research

Background:

• The vasculature is critical for tissue function and disease processes.
• Existing models like spheroids have short-lived vascular components, while iPSC-derived organoids show variable maturation and reproducibility.

Purpose of the Study:

• To develop a consistently formed, free-floating, long-term vascularized mesenchymal organoid (VMO) model.
• To assess the stability, complexity, and physiological relevance of VMOs for biological studies.

Main Methods:

• Co-culturing human umbilical vein endothelial cells (HUVECs) and mesenchymal stromal/stem cells (MSCs) within a minimal Matrigel scaffold.
• Utilizing VMOs to model stromal-tumor interactions and bone marrow metastasis by engrafting breast cancer cells.

Main Results:

• VMOs demonstrated stable vasculature for up to 60 days, showing tissue maturation, inflammation, ECM remodeling, and endothelial development.
• VMOs exhibited enhanced vascular complexity, sustained ECM production, and higher cell viability compared to traditional spheroids.
• The model preserved MSC heterogeneity, including perivascular cells, and successfully modeled stromal-tumor niches for metastasis studies.

Conclusions:

• Consistently formed VMOs provide a robust platform for long-term vascular biology studies.
• This model enables research into stromal dynamics, cancer progression, and bone marrow metastasis.
• VMOs offer potential applications in drug testing and disease modeling.