Rationale Direct conversion or reprogramming of human postnatal cells into endothelial cells (ECs), bypassing stem or progenitor cell status, is crucial for regenerative medicine, cell therapy, and pathophysiological investigation but has remained largely unexplored. Objective We sought to directly reprogram human postnatal dermal fibroblasts (HDFs) to ECs with vasculogenic and endothelial transcription factors (TFs) and determine their vascularizing and therapeutic potential. Methods and Results We utilized various combinations of seven EC TFs to transduce HDFs and found that ER71/ETV2 alone best induced endothelial features. KDR+ cells sorted at day 7 from ER71/ETV2-transduced HDFs showed less mature but enriched endothelial characteristics and thus were referred to as early reprogrammed ECs (rECs), and did not undergo maturation by further culture. After a period of several weeks’ transgene-free culture followed by transient re-induction of ER71/ETV2, early rECs matured during three months of culture and showed reduced ETV2 expression, reaching a mature phenotype similar to postnatal human ECs. These were termed late rECs. While early rECs exhibited an immature phenotype, their implantation into ischemic hindlimbs induced enhanced recovery from ischemia. These two rECs showed clear capacity for contributing to new vessel formation through direct vascular incorporation in vivo. Paracrine or pro-angiogenic effects of implanted early rECs played a significant role in repairing hindlimb ischemia. Conclusions This study for the first time demonstrates that ER71/ETV2 alone can directly reprogram human postnatal cells to functional, mature ECs after an intervening transgene free period. These rECs could be valuable for cell therapy, personalized disease investigation, and exploration of the reprogramming process.

Proof-of-concept was provided for an electrically conductive and nanoroughened microfluidic platform-based chip designed to capture CTCs in patients with EOC. A larger patient sampling and longer duration of follow-up are needed to determine its suitability for clinical use.

Oxidative stress and increased mitochondrial apoptosis may contribute to the pathological process of pelvic organ prolapse.

The aim of the present study was to identify the specific miRNAs involved in regulation of EIF4EBP1 expression in ovarian cancer and to define their biological function. miRNA mimics and miRNA inhibitors were used in quantitative PCR, western blotting, and luciferase reporter assays to assess cell migration, invasiveness, and viability. miR-125a and miR-125b were downregulated in ovarian cancer tissue and cell lines relative to healthy controls. Increased expression of miR-125a and miR-125b inhibited invasion and migration of SKOV3 and OVCAR-429 ovarian cancer cells and was associated with a decrease in EIF4EBP1 expression. The inverse relationship between miR-125a and miR-125b was corroborated by cotransfection of a luciferase reporter plasmid. Furthermore, miR-125a and miR-125b caused apoptosis and decreased cell viability and migration in an apparently EIF4EBP1-directed manner. Collectively, these results indicate that miR-125a and miR-125b are important posttranscriptional regulators of EIF4EBP1 expression, providing rationale for new therapeutic approaches to suppress tumour invasion and migration using miR-125a, miR-125b, or their mimics for the treatment of ovarian cancer.