P4463Combination of allogeneic mesenchymal and kidney stem cells promotes kidney repair in chronic kidney disease

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Background: Chronic kidney disease (CKD) has a high global prevalence estimated at between 11 to 13%. CKD patients are at significantly increased risk of cardiovascular disease (CVD) with a mortality that is 15 times higher than the general population. Current therapies slow disease progression but do not repair organ damage, ultimately leading to end-stage renal disease. Stem cell therapy has the potential to promote repair via neovascularization and antifibrotic effects. Purpose: We tested the renal regenerative capacity of allogeneic mesenchymal stem cells (MSCs) and kidney ckit+ stem cells in an established large animal (swine) model of CKD, the remnant kidney model. Our long-term goal is to identify new therapeutic options for enhancing functional tissue regeneration and preventing the progression of CKD. Methods: Yorkshires pigs (n=27) underwent 5/6 nephrectomy via renal artery embolization using PVA particles and ethanol. At baseline and 4, 8, and 12 weeks post embolization, glomerular filtration rate (GFR), creatinine, BUN, proteinuria, and renal MRI were obtained. Four weeks after embolization, pigs were randomized into 4 groups (n=5 per group): Placebo, MSCs (10×106), c-kit (10×106), and combination group (MSC+c-kit: 1:1 ratio (10×106)). Allogeneic cell therapy was delivered via the patent renal artery of the remnant kidney. At 12 weeks the swine were euthanized.

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