471-P: Transplantation of Apoptosis Resistant Endothelial Progenitor Cells (EPC) May Improve Renal Function in Both Type 1 and 2 Diabetic Kidney Disease (DKD)

Introduction: DKD is associated with glomerulosclerosis and poor perfusion. Transplanting apoptosis resistant p53 silenced (p53sh) EPCs may help to increased vascularization and renal perfusion. EPCs are known to improve perfusion and could be more beneficial than mouse mesenchymal stromal cell (mMSC) transplantation. Method: Hyperglycemia and proteinuria were confirmed at 10 weeks in STZ induced type 1 diabetic C57BL mice and db/db mice for type 2 diabetes mellitus (DM). We transplanted 0.3 million p53sh-EPCs, Null EPCs (control), MSC or saline under each kidney capsule. For type 2 DM model, we also transplanted supernatant of p53sh EPC. Urine was collected weekly for creatinine and protein estimation. Perfusion was measured by renal ultrasound at week 4 post transplantation. Kidneys were harvested for qRT PCR. Results: In type 1 DM model, reduction of protein/creatinine was observed in p53sh EPC transplantation group compared to null and mMSC (1.8 and 1.6 folds, p=0.03. 0.04 respectively) significantly. KDR expression was increased (1.2 fold, p=0.04) on p53sh EPC transplantation compared to null. We observed increased mean and peak renal blood velocity (1.3 folds, p= 0.01, 1.3 fold p=0.001 respectively) in p53sh EPC transplant group compared to null. In type 2 model, 2 fold reduction of protein concentration was noted in p53sh transplanted group compared to null and mMSC groups. Reduction of plasma TNFa, a marker for systemic inflammation was decreased by 2.7 and 1.6 folds in p53sh EPC group in comparison to null-EPC and mMSC respectively. We also noticed that blood glucose level decreased post treatment in all cell therapy groups including the supernatant group, compared to saline, indicating a possible paracrine systemic effect of the cell and supernatant therapy. Conclusion: Transplantation of p53sh EPC improves renal perfusion and renal function in both type 1 and type 2 DM and it is more beneficial than transplantation of mMSC. Disclosure N. Kundu: None. L.D. Asico: None. P.A. Jose: None. S. Sen: None.