Every day our kidneys tackle the daunting task of continuously cleaning our blood to prevent waste, salt, and excess fluid from building up inside our bodies. To achieve this, the kidneys’ approximately 1 million minute filtration units, called glomeruli, first remove both waste products and precious nutrients from the bloodstream. Then, specialized structures known as the proximal tubules reabsorb the “good” molecules — glucose, amino acids, some vitamins, and electrolytes — returning them to the bloodstream.
But the reabsorptive functions of the proximal tubules can be compromised by drugs, chemicals, and genetic and blood-borne diseases. Because our understanding of how these effects occur is still limited, researchers have been working to replicate proximal tubes and other kidney structures in the lab so they can better study their functions, screen drugs without testing on humans or animals, and ultimately use them as a foundation to engineer kidney replacements for diseased or damaged organs.
To help study renal reabsorption, in 2016 Wyss Institute core faculty member Jennifer Lewis and her team — working within the institute’s 3D Organ Engineering Initiative, which she co-leads, and in collaboration with the Roche Innovation Center Basel in Switzerland — created a 3-D proximal tubule model in which fluids could be continuously streamed through the tubules.
While that model removed molecules from the system, however, it lacked a functional blood-vessel compartment for picking up molecules again so they could be reabsorbed by the proximal tubules.
This week, Lewis’ team has presented a solution to that problem: a 3-D vascularized proximal tubule model they created in which independently perfusable tubules and blood vessels are printed adjacent to each other within an engineered extracellular matrix. Their study is published in the Proceedings of the National Academy of Sciences (PNAS).
“We construct these living renal devices in a few days and they can remain stable and functional for months,” said first author Neil Lin, a Roche Fellow and a postdoctoral fellow on Lewis’ team. These 3-D vascularized proximal tubules, Lin continued, demonstrate that the team’s multitissue constructs are indeed mature and functional. “[They] exhibit the desired epithelial and endothelial cell morphologies and luminal architectures, as well as the expression and correct localization of key structural and transport proteins and factors that allow the tubular and vascular compartments to communicate with each other,” he said.