Controlled Delivery of Stem Cell‐Derived Trophic Factors Accelerates Kidney Repair After Renal Ischemia‐Reperfusion Injury in Rats

• Published in: Stem cells translational medicine 2019-09, Vol.8 (9), p.959-970
• Main Authors: Yim, Hyung Eun, Kim, Doo Sang, Chung, Hyun Chul, Shing, Brian, Moon, Kyung Hyun, George, Sunil K., Kim, Michael W., Atala, Zachary, Kim, Ji Hyun, Ko, In Kap, Yoo, James J.
• Format: Article
• Language: English
• Subjects: Acute kidney injury; Cell growth; Cell proliferation; Cell survival; Conditioned medium; Controlled release; Cytokines; Data analysis; Dialysis; Drug delivery systems; Erythropoietin; Growth factors; Hydrogels; Ischemia; Kidney diseases; Kidney regeneration; Kidney transplantation; Laboratory animals; Medicine; Placenta; Recovery of function; Reperfusion; Stem cells; Structure-function relationships; Studies; Tissue engineering; Tissue Engineering and Regenerative Medicine; Trophic factors; Vehicles
• ISSN: 2157-6564; 2157-6580
• DOI: 10.1002/sctm.18-0222

Renal disease is a worldwide health issue. Besides transplantation, current therapies revolve around dialysis, which only delays disease progression but cannot replace other renal functions, such as synthesizing erythropoietin. To address these limitations, cell‐based approaches have been proposed to restore damaged kidneys as an alternative to current therapies. Recent studies have shown that stem cell‐derived secretomes can enhance tissue regeneration. However, many growth factors undergo rapid degradation when they are injected into the body in a soluble form. Efficient delivery and controlled release of secreting factors at the sites of injury would improve the efficacy in tissue regeneration. Herein, we developed a gel‐based delivery system for controlled delivery of trophic factors in the conditioned medium (CM) secreted from human placental stem cells (HPSCs) and evaluated the effect of trophic factors on renal regeneration. CM treatment significantly enhanced cell proliferation and survival in vitro. Platelet‐rich plasma (PRP) was used as a delivery vehicle for CM. Analysis of the release kinetics demonstrated that CM delivery through the PRP gel resulted in a controlled release of the factors both in vitro and in vivo. In an acute kidney injury model in rats, functional and structural analysis showed that CM delivery using the PRP gel system into the injured kidney minimized renal tissue damage, leading to a more rapid functional recovery when compared with saline, CM, or vehicle only injection groups. These results suggest that controlled delivery of HPSC‐derived trophic factors may provide efficient repair of renal tissue injury. Stem Cells Translational Medicine 2019;8:959&970 Schematic diagram of efficient delivery of conditioned medium (CM) for treatment of acute kidney injury created by ischemia/reperfusio in rats. For sustained release of CM within the damaged kidney, platelet‐rich plasma (PRP) was used as a delivery vehicle. Intrarenal injection of the CM encapsulated into the PRP effectively facilitated restoration of renal functions compared with experimental controls.