Transforming Kidney Care Through Tissue Engineering

Every year, thousands of patients with kidney failure face the same stark reality: Dialysis keeps them alive, but their quality of life is significantly reduced. Dialysis cannot replace all the complex functions of a healthy kidney. Meanwhile, the demand for donor kidneys far outstrips supply, leaving many patients waiting years. Some never receive a transplant.

This urgent gap between need and availability has motivated Yale School of Medicine’s William Chang, MD, PhD, to search for solutions. His lab explores how tissue engineering—using stem cells, organ-on-a-chip devices, and engineered microvasculature—might one day offer new alternatives.

In a Q&A, the assistant professor of medicine (nephrology) reflects on his journey into the field and his recent breakthroughs.

I first found my passion for research as an undergrad studying bacterial motility and later explored telomere biology during my MD-PhD. After completing my internal medicine residency and first year of nephrology fellowship at Yale, I joined the lab of Jordan Pober, MD, PhD, who was engineering human microvessels to model human endothelial cell immunology.

After learning how to make these microvessels in animal model systems, I started growing them on small chips (about the size of a microscope slide) in lab incubators. Watching cells organize into microvasculature was eye-opening and made me wonder: Could those same principles be applied to the kidney? That’s how I found my path into tissue engineering in nephrology.

Dialysis keeps patients alive but replaces only some parts of kidney function, and thus morbidity and mortality on dialysis remain too high. Although significantly better, kidney transplants are limited by shortages of transplantable kidneys and concerns about kidney transplant rejection. Patients need to take immunosuppressant medications chronically, and these can have significant side effects.

Tissue engineering offers another path. We are exploring the use of stem cell-derived kidney tissue, called kidney organoids, that could be derived from patients themselves. This could theoretically overcome immunological limitations. One major focus of our lab is to see if these tissues can be functional.

Microvasculature chips are small devices we use to grow blood vessel cells under vascular flow—the controlled movement of liquid that mimics blood circulation—which helps the cells organize and form stable, lifelike perfusable microvessels that resemble capillaries. The chips let us study how diseases like diabetes damage small vessels in ways that simple culture systems can't.

Kidney organoids are miniature kidney-like structures made from stem cells. The stem cells are instructed to differentiate into many of the cell types found in actual kidneys, but the cells also organize themselves into some of the key structures found within the kidney like microvessels and kidney tubules.

What excites me most is their potential—not just for modeling genetic diseases and testing drugs, but for achieving true kidney function.

The types of tissue-engineered systems that we are using are already applied to drug testing and disease modeling. But, in terms of replacement therapy, we’re much further off. While stem cell tissues could one day offer patient-specific solutions, we probably won’t be engineering a full kidney soon. But even providing partial kidney function, like 20% of normal, could make a big difference.

The natural kidney is incredibly complex, but people can remain healthy with a fraction of normal kidney function. If we could design a construct that delivers even part of that function reliably, it could transform care. We may find creative ways to engineer devices or tissues that don’t resemble kidneys in shape but still accomplish the essential job of filtering, modifying blood, and providing endocrine function.

Nephrology is one of 10 sections in the Yale Department of Internal Medicine. Committed to excellence in patient care, research, and education, the section’s faculty and trainees aim to be national and international leaders in academic nephrology. To learn more, visit Nephrology.