Mesenchymal-like progenitors derived from human embryonic stem cells promote recovery from acute kidney injury via paracrine actions

Background aims. The engraftment of mesenchymal stem cells (MSCs) is reported to promote recovery of renal function in animal models of acute kidney injury (AKI). However, it is unknown whether mesenchymal-like progenitors (MPs) derived from human embryonic stem cells (hESCs) can mediate similar therapeutic effects. We investigated the responses of recipient renal tissue to engraftment of hESC-MPs and underlying mechanisms of these effects. Methods. We measured blood urea nitrogen and creatinine levels of AKI mice with hESC-MPs transplantation and control mice. We performed renal morphology analysis by immunohistochemistry and electron microscopy to confirm the renoprotective effects of engrafted hESC-MPs. Proliferation, apoptosis and gene expression of tubular cells were also monitored by immunohistochemistry and real-time quantitative polymerase chain reaction to investigate the mechanisms that occurred. Results. After transplantation of hESC-MPs into mice with cisplatin-induced AKI, improvements in renal function and recovery from tubular epithelial cell injury were observed. Engrafted hESC-MPs were localized to areas of injured kidney 5 days after cisplatin induction, where they promoted tubular cell proliferation and decreased kidney cell apoptosis. The beneficial effect was further confirmed by the capability of the engrafted cells to up-regulate renal gene expression of anti-inflammatory cytokines and pro-survival cytokines. Meanwhile, infusion of these cells reduced renal gene expression of pro-inflammatory cytokines and monocyte chemotactic protein-1, a chemokine that stimulates monocyte and macrophage infiltration. Conclusions. Our results show that infused hESC-MPs may promote recovery from AKI by regulating related cytokines.