Microvascular engineering: Dynamic changes in microgel-entrapped vascular cells correlates with higher...

Area of Science:

• Regenerative Medicine
• Tissue Engineering
• Vascular Biology

Background:

• Developing effective strategies for neovascularization of ischemic tissues is crucial for regenerative medicine.
• Microparticles offer potential for minimally-invasive therapeutic vascularization, but in vitro cellular changes during morphogenesis are not well understood.

Purpose of the Study:

• To investigate the use of bioengineered microgels to guide the assembly of endothelial cells and stem cells into vascularized microtissues.
• To analyze cellular alterations and secretome changes during in vitro maturation.
• To evaluate the therapeutic potential of matured microtissues after transplantation.

Main Methods:

• Utilized bioengineered microgels to co-culture outgrowth endothelial cells (OEC) and mesenchymal stem cells (MSC).
• Monitored in vitro vascular morphogenesis, including network formation and extracellular matrix deposition.
• Performed gene expression profiling to assess cellular phenotypes and secretome analysis.
• Evaluated cell survival, retention, and vascular structure formation after transplantation in mice.

Main Results:

• Microgels successfully guided OEC and MSC assembly into vascularized microtissues with capillary-like networks.
• OEC exhibited a partial endothelial-to-mesenchymal transition (EndMT) during maturation, while MSC remained stable.
• The secretome became more pro-angiogenic without significant inflammatory changes.
• Transplanted microgels demonstrated enhanced cell survival, network preservation, and de novo human vascular structure formation.

Conclusions:

• In vitro priming and morphogenesis within microgels enhance the vasculogenic and angiogenic potential of endothelial and stem cells.
• This approach improves cell survival and vascularization after transplantation, highlighting therapeutic relevance for ischemic conditions.
• The study sheds light on the mechanisms underlying improved therapeutic outcomes through pre-vascularized microtissues.