A team from CAS Institute of Biophysics, Institute of Zoology and Peking University has prepared human vascular cells with improved self-renewal and increased resistance to oxidative injury. In human ESC-derived vascular cells, they engineered FOXO3, an evolutionarily conserved longevity factor, to a more stable homolog by replacing two nucleotides in exon 3 of the FOXO3 gene that inhibit the phosphorylation and subsequent nuclear export and degradation of FOXO3, thus promoting the nuclear translocation of the FOXO3 protein and expression of its target genes. When tested in a therapeutic context in a mouse model, these cells promoted vascular regeneration of ischemic injury and were resistant to tumorigenic transformation both in vitro and in vivo. Mechanistically, constitutively active FOXO3 conferred cytoprotection by transcriptionally downregulating CSRP1. The study is seen as a promising option for future regenerative medicine.
CAS news release, January 18, 2019