Researchers at Penn Engineering’s Hughes Lab have discovered key mechanical signals in kidney development, paving the way for engineering artificial kidneys. This breakthrough could revolutionize treatment for chronic kidney disease, affecting millions worldwide.
Kidney disease remains one of the most daunting health challenges globally, but inspiring advancements at the Hughes Lab at the University of Pennsylvania may signal a transformative leap forward. Researchers have uncovered crucial mechanical cues that could guide the development of artificial kidney tissue, offering new hope for millions suffering from chronic kidney disease (CKD).
Densely packed with tubules known as nephrons, kidneys are vital for filtering blood, regulating blood pressure and maintaining fluid balance. However, the kidney’s limited capacity to regenerate makes diseases like CKD particularly devastating.
“There is a huge clinical burden of kidney disease,” Alex Hughes, assistant professor in bioengineering within Penn Engineering and in cell and developmental biology within Penn Medicine, said in a news release. “And there are relatively few engineers trying to come up with new solutions.”
The numbers are stark. CKD affects over 850 million people worldwide, including more than one in seven Americans. Many patients remain unaware of their condition until it progresses significantly, leading to kidney failure — an outcome entailing either dialysis or transplantation. With a U.S. transplant waiting list around 100,000 and a three- to five-year wait time, the present solutions are far from ideal.
Seeking to address this, the Hughes Lab has zeroed in on the mechanisms behind kidney formation. Kidneys develop like forests of pipes, with nephrons forming as tubules branch and react to their environment. Hughes and his team discovered these tubules generate tiny mechanical stress waves as they grow, explaining the variable number of nephrons in each kidney.
“It’s like a city’s water distribution network,” Hughes added, “but it’s being built by these cells that somehow collectively know what to build and where their neighbors are and what junctions to make, all without a blueprint.”
In a recent paper published in the journal Nature Materials, the team identified these stress waves as a potential signpost for nephron formation. By simulating this rhythm, they aim to guide the creation of artificial kidneys — an approach that could ultimately bypass the need for dialysis and transplantation altogether.
The complexity of this task cannot be understated. Current artificial kidney tissues, or organoids, lack the ordered structure necessary for effective function.
“You can create the right cell types,” added Hughes, “but their spatial organization is incorrect for the most part.”
These misalignments prevent organoids from functioning like natural kidneys, which precisely filter waste and ensure it exits the body.
The Hughes Lab is overcoming these challenges by developing custom microwells that facilitate the optimal conditions for kidney tissue growth.
A second paper published in Cell Systems highlights their strategy of creating tiny cell communities in controlled ratios to form a “goldilocks” ratio for optimal organoid composition.
“If we change the ratio, we see quite different compositions of the organoid,” Hughes said. “So you can treat these as designer organoids where you have control over the outcome.”
The lab’s dual insights into mechanical stress waves and precise cell ratios offer a promising blueprint for future kidney tissue engineering.
“You can imagine as these organoids are differentiating, you could simulate that rhythmic process and see if suddenly you can kick off a larger-scale outcome,” Hughes added.
As CKD is projected to become the fifth-leading cause of years of life lost globally by 2040, the urgency of the Hughes Lab’s research cannot be overstated.
“I think there’s just enormous opportunity to think about synthetically reconstituting kidney tissues for regenerative medicine,” Hughes added, looking toward a future where innovation and science meet to alleviate a significant global health burden.