Use of p53-Silenced Endothelial Progenitor Cells to Treat Ischemia in Diabetic Peripheral Vascular Disease.

BackgroundPeripheral vascular disease is a major diabetes mellitus‐related complication. In this study, we noted that expressions of proapoptotic p53 gene and its downstream cascade gene such as p21 are upregulated in hyperglycemia. Therefore, we investigated whether p53‐ and p21‐silenced endothelial progenitor cells (EPCs) were able to survive in hyperglycemic milieu, and whether transplantation of either p53 knockout (KO) or p21KO or p53‐ and p21‐silenced EPCs could improve collateral vessel formation and blood flow in diabetic vaso‐occlusive peripheral vascular disease mouse models. Methods and ResultsWe transplanted p53 and p21KO mouse EPCs (mEPCs) into streptozotocin–induced diabetic (type 1 diabetes mellitus model) C57BL/6J and db/db (B6.BKS(D)‐Leprdb/J) (type 2 model) post–femoral artery occlusion. Similarly, Ad‐p53–silenced and Ad‐p21–silenced human EPCs (CD34+) cells were transplanted into streptozotocin‐induced diabetic NOD.CB17‐Prkdcscid/J mice. We measured blood flow at 3, 7, and 10 days and h...