Winning Solution: Draining Artificial Kidneys by Connecting Synchronized Nephrons to Synthetic Organizers​

The function of the kidney is to receive one fifth of the cardiac output and filter and maintain the blood’s composition. Compounds that are required by the body are reabsorbed by specialized nephron cell-types, while unwanted metabolites are excreted to the bladder through an epithelial collecting duct system. A large portion of the Medicare budget (>$50 billion or 7%) is spent on patients with End-Stage Renal Disease (ESRD) where normal kidney function is lost (not including private costs), a figure that is constantly rising. For infants born with ESRD there are no corrective or therapeutic options beyond dialysis and organ transplantation; with a mortality rate at 93% within the first year of life. ESRD broadly affects all US racial groups, but Hispanics are ~1.5 times more likely to develop ESRD while Black Americans represent ~35% of all ESRD cases in the US. Kidney disease therefore places a considerable burden on health care systems, private and government funding, and patients.

Stem cell-based systems hold great promise for providing regenerative therapies alleviating kidney disease and human kidney models that can lead to safer therapeutics with reduced nephrotoxic side effects. These cellular therapies and models often aim to make “synthetic” or “artificial” kidneys, either for drug screening in vitro, or for dialysis alternatives in vivo. While effort has been placed on vascularizing artificial nephrons, considerably less work has been performed to understand how they can be connected to a drainage system. Without a connection to a drainages system, any artificial kidney would lack the capacity to drain the unwanted filtrate (urine), making it impossible to use the construct either for in vitro studies or in vivo replacements. Our team’s goal is to generate functional artificial kidneys from stem cells, suitable for both drug discovery and serving as bioartificial kidneys. We generate construct in vitro and connect artificial nephrons to a common drainage system. This will move the field of artificial kidneys a decisive step forward towards clinical applications and be the basis of the construction of a functional filtration unit in vitro.

Dr. Lindström earned his Ph.D. in developmental biology at the University of Edinburgh (UK) detailing mechanisms underpinning kidney development. He continued this work at the MRC Human Genetics Unit  (UK), Roslin Institute (UK), and the University of Southern California  (USA) describing how the functional unit of the kidney, the nephron, forms during human embryogenesis. Since starting his own research team at the University of Southern California, his group now scrutinizes cellular diversity-forming genetic programs in the nephron and use the insights they produce to build artificial kidney systems that generate mature nephron cells from stem cells.