Bone marrow-derived mesenchymal stromal cells enhance chimeric vessel development driven by endothelial cell-coated...

Area of Science:

• Regenerative Medicine
• Tissue Engineering
• Vascular Biology

Background:

• Rat aortic endothelial cells (RAECs) formed vessels in vivo but resulted in leaky, inflamed vasculature.
• Bone marrow-derived mesenchymal stromal cells (bmMSCs) were investigated to improve vascularization.
• Modular tissue engineering utilizes microtissues for constructing larger functional tissues.

Purpose of the Study:

• To evaluate the impact of embedding bmMSCs into endothelialized collagen gel microtissues on vessel formation and stability.
• To investigate the in vivo behavior and pericyte-like potential of transplanted bmMSCs.
• To assess the immunomodulatory effects of bmMSCs in an allogeneic transplant model.

Main Methods:

• Endothelialized collagen gel microtissues were created with and without embedded bmMSCs.
• Microtissues were transplanted into immunosuppressed Sprague-Dawley rats.
• Vessel formation, stability, and leakage were assessed using microcomputed tomography (microCT) perfusion.
• Immunohistochemistry was used to analyze macrophage infiltration and bmMSC differentiation.

Main Results:

• Embedding bmMSCs enhanced endothelial cell proliferation and sprouting in vitro.
• In vivo, bmMSC co-transplantation resulted in more stable, less leaky vessels compared to endothelial cells alone.
• bmMSCs reduced inflammatory macrophage infiltration and exhibited smooth muscle actin expression, adopting pericyte-like morphology.
• Transplanted bmMSCs integrated into the vessel wall, surrounding the endothelial cell layer.

Conclusions:

• Bone marrow-derived mesenchymal stromal cells significantly improve the stability and reduce leakage of engineered vascular structures.
• The pericyte-like behavior and immunomodulatory effects of bmMSCs are key to enhancing vascularization in tissue engineering.
• Modular tissue engineering combined with bmMSCs holds promise for creating functional vascularized tissues.