Method for reducing carcinogenicity of induced pluripotent stem cells derived from aged donors

摘要

(A) Induced pluripotent stem cells (A-iPSCs) from aged donors compared to those from young donors (A-iPSC) are associated with increased genomic instability, abnormal apoptosis, abnormal glucose metabolism, (B) inhibition of excessive glutathione-mediated H2O2 ablation activity which was found to be associated with A-iPSC and consequently inhibited DNA damage response and apoptosis, these abnormalities To substantially reduce the carcinogenic potential of A-iPSC. Supplementation of the pluripotency factor ZSCAN 10 (low activity at A-iPSC and shown to act on glutathione-related upstream), such as by expression as an aid of four Yamanaka iPSC reprogramming factors, In A-iPSC, it results in a significant recovery of genomic stability, DNA damage response and apoptosis through enhancement of GLUT 3 and normalization of glutathione / H 2 O 2 homeostasis; GLUT 3 (acting upstream of glutathione and also active in A-iPSC A low pluripotent stem cell specific glucose transporter) has a similar effect, particularly inhibition of glutathione / H 2 O 2 by delivery of ZSCAN 10 and / or GLUT 3 and / or exosomal subunits is clinically useful, improved Characteristics and low It indicates that result in the carcinogenic A-iPSC. BACKGROUND OF THE INVENTION