Implant renal injury-responsive cells to supplement erythropoietin and protect kidney

Anemia poses a life-threatening risk to individuals with chronic kidney diseases (CKDs). Insufficient production of erythropoietin (EPO) from injured kidney is the major reason for anemia, while lack of EPO would further aggravate the kidney injury and make a “vicious cycle”. In this study, we dissected the change of endogenous EPO signaling in injured kidney by spatial transcriptomic analysis and validated the dual beneficial effects of local recombinant EPO administration on both anemia correction and kidney protection. Next, we constructed an injury-responsive EPO producing (iREP) element to sense the kidney damage signal and drive the synthesis and secretion of native EPO. After intra-renal implantation of iREP engineered HEK-293T embryonic kidney cells, the mouse kidney would automatically produce more EPO when sensing injury signal, which in turn enhanced red blood cell mass and protected kidney from further injury. Moreover, aided with automated equipment, we cloned urine-derived SOX9+ epithelial cells (USCs) from both healthy donors or CKD patients. The USCs could be transplanted into mouse kidney and form tubule-like structures, which makes them an alternative candidate cell for iREP engineering. Altogether, the current work proposed a potential approach based on engineered “smart” cell to treat CKDs.