Korean Circ J.  2022 Sep;52(9):643-658. 10.4070/kcj.2022.0190.

Generation and Application of Directly Reprogrammed Endothelial Cells

• Jung C
• Oh JE
• Lee S
• Yoon Ys

• KMID: 2532931
• DOI: http://doi.org/10.4070/kcj.2022.0190

Abstract

Cell-based therapy has emerged as a promising option for treating advanced ischemic cardiovascular disease by inducing vascular regeneration. However, clinical trials with adult cells turned out disappointing in general. As a newer approach, direct reprogramming has emerged to efficiently generate endothelial cells (ECs), which can promote neovascularization and vascular regeneration. This review provides recent updates on the direct endothelial reprogramming. In general, directly reprogrammed ECs can be generated by two approaches: one by transitioning through a plastic intermediate state and the other in a one-step transition without any intermediate states toward pluripotency. Moreover, the methods to deliver reprogramming factors and chemicals for the fate conversion are highlighted. Next, the therapeutic effects of the directly reprogrammed ECs on animal models are reviewed in detail. Other applications using directly reprogrammed ECs, such as tissue engineering and disease modeling, are also discussed. Lastly, the remaining questions and foremost challenges are addressed.

Keyword

Cardiovascular disease; Direct cell reprogramming; Endothelial cells; Neovascularization; Cell differentiation and regenerative medicine

Figure

• 

  Figure 1 Schematic of direct endothelial reprogramming. Somatic cells can be reprogrammed into iPSCs, which possess the full pluripotent state, and be differentiated into ECs with lineage-specific factors. In direct reprogramming, somatic cells can be transdifferentiated into ECs via two different processes: (a) transit through a plastic state or (b) direct conversion. In (a), brief exposure to reprogramming factors followed by conditioned media allows the somatic cells to be converted into ECs without achieving the pluripotency. In (b), introduction of endothelial lineage-specific transcription factors and small molecules allows the somatic cells into ECs.EC = endothelial cell; iPSC = induced pluripotent stem cell.

• 

  Figure 2 Applications of directly reprogrammed EC. Directly rECs can be used for therapeutic applications, including cell-based therapy, tissue engineering, and disease modeling and potential drug screening and development.EC = endothelial cell.

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