Reprogrammed Human Endothelial Cells

Abstract

Nothing in nature is more elegant than the transformation of fertilized oocyte into a unique and complex individual containing some 10 trillion cells with more than 200 specialized functions. Also astonishing, however, is that a cell’s career decision is not necessarily permanent, but can be reversed. Committed specialized somatic cells can, in effect, go back and start again from scratch. The generation of induced pluripotent cells, reported first by Takahashi and Yamanaka1 and now generated routinely in laboratories all over the world clearly demonstrates that differentiated somatic cells can be reprogrammed into a cell of desired phenotype. This concept of transcription factor (TF)–based alterations in a cell’s identity was further demonstrated by several reports attempting direct reprogramming of a differentiated somatic cells into another differentiated somatic cell without the need for pushing the reprogrammed cell to a pluripotent state, a method now known as “direct reprogramming.”2,3 In this issue of Circulation Research, Lee et al4 report their success in reprogramming human dermal fibroblasts (HDFs) into functional and mature endothelial cells (ECs) using a single EC TF ER71/ETV2 (E-26 variant 2). This approach opens a novel era in translational cardiovascular medicine by increasing the availability of autologous ECs to be used in cell-based vascular regenerative therapy.Article, see p 848Derivation of engraftable human ECs could be beneficial to patients with vascular diseases. However, purification and expansion of adult ECs in therapeutically large numbers is technically challenging. Embryonic stem cells and induced pluripotent cells serve as promising alternatives for ECs generation and potentially provide great therapeutic potential; however, several problems limit the clinical applications of derivative cells, including inefficient cell production, long duration of cell culture, and tumorigenic potential.5 Recently, the ability to directly reprogram accessible human cells into disease-relevant cell types through cellular …