Seonggeon Cho
BME PhD Defense Presentation

Date: 2026-05-06
Time: May 6th 1PM-3PM
Location / Meeting Link: N600/https://timeful.app/e/ab778

Committee Members:
Yoon, Young-sup Jo, Hanjoong Davis, Michael E Hee Cheol Cho Lee, Sang-Ho 


Title: DIRECT CONVERSION OF HUMAN SOMATIC CELLS INTO VASCULAR TISSUE

Abstract:
Background: Directly reprogrammed endothelial cells generated using the endothelial lineage–specific transcription factor Ets variant 2 (ETV2) show promise for treating ischemic cardiovascular diseases, but clinical translation remains limited by challenges in cell sourcing, safe gene delivery, and survival in ischemic tissue. To address this, we developed a direct reprogramming strategy using human urine-derived cells (U-cells) and adenoviral ETV2 (Ad-ETV2) to generate a vascular tissue–like structure comprising endothelial cells (ECs), perivascular cells, and extracellular matrix (ECM). Method: U-cells from healthy male donors were transduced with Ad-ETV2 and cultured with ascorbic acid to promote ECM deposition and endothelial growth factors to induce differentiation. Endothelial characteristics were evaluated by qRT-PCR, flow cytometry, immunostaining, and single-cell RNA sequencing. ECM composition was analyzed by liquid chromatography–mass spectrometry. Therapeutic efficacy was assessed in a murine hindlimb ischemia model using laser Doppler perfusion imaging, histological analysis, and gene expression profiling of ischemic tissue. Result: By day 10, robust ECM deposition enabled harvest of cells in tissue form. The resulting directly reprogrammed vascular tissue-like structure (rVT) contained 75–86% EC-like and mesenchymal stromal cell–like populations, confirmed at the mRNA, protein, and cellular levels, along with key structural and vessel-specific ECM proteins. rVT displayed a pre-vascularized architecture, and transplantation into ischemic mouse hindlimbs significantly improved blood perfusion, reduced tissue damage, and enhanced angiogenic and arteriogenic paracrine signaling. Tissue-form transplantation showed superior engraftment over dissociated cell injection. Transplanted cells migrated into host tissue, incorporating directly into vessels or localizing perivascularly — exhibiting pericytic behavior or residing within the ACTA2-positive layer of small arterioles. These vasculogenic and arteriogenic effects persisted for up to 3 months post-transplantation. Conclusion: rVT containing endothelial-like cells can be efficiently generated from U-cells via Ad-ETV2 transduction. Transplantation improves blood flow recovery, enhances tissue protection, and provides sustained vasculogenic and arteriogenic effects in ischemic tissue. This direct tissue reprogramming strategy offers a clinically relevant approach by simultaneously generating vascular cells and supportive ECM from autologous sources, eliminating the need for synthetic biomaterials or complex purification steps.