Engineered Subcutaneous Site for Optimal Organoid Transplantation

Abstract

The subcutaneous space is an advantageous site for cell transplantation because of its minimally invasive accessibility. However, poor vascularization often compromises cell survival, leading to significant apoptosis of transplanted cells. To address this limitation, we engineered a pre-vascularized niche by subcutaneously implanting polyvinyl chloride (PVC) catheters into rodent models. Foreign body reactions elicited by PVC catheters recruited reparative immune cells, which secreted pro-angiogenic factors to induce robust neovascularization. The subsequent transplantation of stem cell-derived vascular organoids into this engineered niche resulted in optimal engraftment, forming functional, perfused human blood vessels. In a proof-of-concept islet transplantation model, even a marginal dose of islets rapidly restored normoglycemia, which was attributed to enhanced graft revascularization. Collectively, our findings demonstrate a simple yet effective strategy for overcoming the vascular limitations of subcutaneous cell transplantation, offering promising potential for clinical applications.