Session: PD19: Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II
PD19-03: The Delivery of the Recombinant Protein Cocktail Identified by Stem Cell-Derived Secretome Analysis Accelerates Kidney Repair After Renal Ischemia-Reperfusion Injury
Introduction: Renal disease is a worldwide health issue. Stem cell therapies have been proposed to restore damaged kidneys as an alternative to renal replacement therapies. In addition to stem cell therapies, recent studies have shown that stem cell-derived secretomes or conditioned media (CM) can enhance tissue regeneration. Our previous study demonstrated that the controlled delivery of human placental stem cells (hPSC)-derived CM using platelet-rich plasma (PRP) improved histological and functional recovery in an acute kidney injury (AKI) model in rats. The protein analysis of hPSC-CM showed the five highly expressed proteins that promote kidney repair. Based on our results, we propose that these proteins could be used as a recombinant protein cocktail to treat kidney diseases as an alternative to using CM. This study investigated the feasibility of delivering the recombinant protein cocktail for kidney repair after AKI. Methods: The effects of the recombinant protein cocktail on human renal cell survival, proliferation, and apoptosis were compared with the CM in vitro. The feasibility of delivering the recombinant protein cocktail with a PRP system to achieve structural and functional recovery after AKI was investigated. Results: The pro-proliferative and anti-apoptotic effects of the protein cocktail on renal cells were demonstrated in vitro and in vivo. The intrarenal delivery of these proteins with PRP ameliorates the renal tubular damage and improved renal function in the AKI-induced rats, yielding similar therapeutic effects compared to the CM delivery. Conclusions: The delivery of RPC can support renal cell survival and proliferation in vitro and in vivo, resulting in the attenuation of renal tubular damages and amelioration of renal function in the AKI model in rats. Our strategy may provide a therapeutic solution to many challenges associated with kidney repair resulting from the lack of suitable off-the-shelf regenerative medicine products. SOURCE OF Funding: This work was supported by the State of North Carolina.
