Recreating the perivascular niche ex vivo using a microfluidic approach

Area of Science:

• Biomedical Engineering
• Stem Cell Biology
• Vascular Biology

Background:

• Stem cell niches, crucial for tissue homeostasis, often feature proximity to vasculature.
• Adult stem cells like mesenchymal stem cells (MSCs) are commonly found near blood vessels.
• Understanding the molecular regulation of these perivascular stem cell niches is essential.

Purpose of the Study:

• To develop and characterize a novel 3D microfluidic device (MFD) for studying perivascular stem cell niches.
• To investigate the interaction between endothelial cells (ECs) and stromal cells (MSCs or fibroblasts) in a vascularized niche model.
• To elucidate the molecular mechanisms governing stem cell-endothelial cell interactions in the niche.

Main Methods:

• Fabrication of a 3D microfluidic device containing fibrin gels.
• Co-culture of endothelial cells (ECs) with either bone marrow-derived mesenchymal stem cells (MSCs) or fibroblasts.
• Observation of vasculogenesis and capillary network formation.
• Biochemical assays to identify molecular interactions, including integrin-laminin binding.

Main Results:

• The MFD successfully modeled perivascular stem cell niches, enabling ECs to form capillary networks.
• Both MSCs and fibroblasts associated with ECs, but influenced capillary morphogenesis differently.
• MSCs' perivascular association was mediated by the α6β1 integrin receptor interacting with endothelial cell-deposited laminin.
• The model demonstrated physiological relevance for studying stem cell-vasculature interactions.

Conclusions:

• The novel 3D MFD provides a physiologically relevant platform for studying perivascular stem cell niches.
• Perivascular association is critical for stem cell behavior and is regulated by specific molecular interactions.
• This model system can advance the understanding of how vascular proximity influences stem cell multipotency and tissue homeostasis.