Seonggeon Cho

BME PhD Proposal Presentation

Date: 2023-07-24
Time: 1PM-3PM
Location / Meeting Link: HSRB2 N257/Zoom: [https://emory.zoom.us/j/96328576662]

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


Title: Direct Conversion of Urine-derived Cell into Vascular Tissue-like Structure using ETV2

Abstract:
Ischemic cardiovascular diseases are the leading causes of morbidity and mortality across countries. While various medical, surgical, and interventional therapies are available, treating patients with advanced cases and multiple comorbidities remain challenging. Underlying burden of the diseases are loss of vascular supply and inability to restore vessel with endogenous mechanism. Cell therapy, as it supplies functional endothelial cells (ECs), is an attractive strategy for neovascularization. After over all failure in adult stem or progenitor cells, human pluripotent stem cell (hPSC) has emerged as a source for EC generation. Although ECs differentiated from hPSCs successfully induced vascular regeneration, differentiating volatility and tumorigenic potential remain as concerns for clinical translation. Alternatively, direct reprogramming strategy was employed that uses lineage-specific transcription factors (TFs) to generate the target cells without achieving pluripotency. ETV2, ETS TF family that binds to the promoters of key EC related genes, has emerged as a candidate pioneering factor for endothelial reprogramming. Our lab successfully generated EC from human dermal fibroblast (HDF) by transiently activating ETV2 with doxycycline (DOX)-inducible lentiviral vectors. The reprogrammed ECs (rECs) demonstrated robust neovascularization potential both in vitro and in vivo models. However, low survival of transplanted cells in ischemic tissue poses a critical barrier for cell therapy. Regardless of which cell types and which ischemic models are used, low retention of transplanted cells is evident. This fact questions the advantage of using reprogrammed cells over adult cells if they function through short-term paracrine effects without durable vascular incorporation. Biomaterials and coadministration of ECs and perivascular or supportive cells have shown to enhance cell survivor. Perhaps simultaneous generation of both therapeutic cells and biosacffold would provide excellent solution for long-term survivor of therapeutic cells and sustained vessel formation. Here we demonstrate generation of tissue from human adult cells with direct reprogramming strategy. The tissue can supply both critical cells for neovascularization and ECM to enhance cell survival. Methods to generate tissue organoid have been tried with PSC derived cells, but our study is first to demonstrate generation of tissue from human adult somatic cells with single TF.