the blood vessels, and another for the surrounding supportive tissue. Achieving the correct ratio and spatial arrangement of these stem cells is essential for effective kidney tissue development. “Creating these tissues is like baking a cake,” Hughes explains. “You need the right ingredients in the right amounts to get something that resembles a kidney.”
Progress in scaling up the production of kidney organoids and improving their organization is ongoing. Researchers are experimenting with various factors, such as the biochemical environment and mechanical cues, to refine the growth of these tissues. The ultimate goal is to develop fully functional kidney tissues that can one day serve as replacements for damaged organs.
Looking Ahead
While these advancements are promising, the path to clinical applications involves overcoming numerous challenges, including ensuring the survival and integration of artificial tissues once implanted into the human body. Hughes emphasizes the importance of collaborating across multiple disciplines—engineering, biology, and medicine—to make significant strides in this field. “It’s a complex puzzle,” he notes, “but we’re learning more about how to piece it together.”
The hope is that through continued research, developments in kidney tissue engineering could lead to more effective treatments for chronic kidney disease, ultimately improving the quality of life for millions affected by this condition.
The nephrons serve a primary function, while the supportive structures include blood vessels. In contrast to gut organoids, which can be created from a single type of stem cell to model intestinal tissue, kidney organoids present a more complex challenge.
A recent publication in Cell Systems by the Hughes Lab introduced an innovative approach: constructing small groups of various cell types arranged in a mosaic pattern. By modifying the proportions of each type of stem cell, the researchers could effectively alter the organoid’s makeup.
First author Catherine Porter, along with coauthors Samuel Grindel, both doctoral students in Bioengineering, and Grace Qian, a 2023 Bioengineering graduate now pursuing a doctorate at the University of California Berkeley and the University of California San Francisco, designed custom microwells. Using these, they tested different mixes of kidney stem cells, akin to bakers experimenting with recipes.
As they varied the ratios, the researchers identified a “peak” in tubule production, pointing to an ideal cell composition for kidney tissue growth, which they referred to as the “goldilocks” ratio. “Adjusting the ratio results in significantly different organoid structures,” Hughes explains. “This allows us to create designer organoids with control over the final outcome.”
Translating Research to Clinical Use
Ultimately, Hughes aspires to integrate these two insights—understanding mechanical stress waves that affect kidney development and the proportions affecting organoid structure—into practical clinical applications. “As these organoids develop,” he notes, “simulating that rhythmic process might trigger a broader development response.”
The necessity for alternatives to kidney transplants and dialysis cannot be overstated. With the current demand, there will never be enough kidneys available for transplantation. “This is a significant gap that engineers can aim to bridge,” Hughes states. In his workspace, he keeps his great-grandfather’s pocket watch as a symbol of how form and function are intertwined in the design of complex mechanical devices. The watch continues to keep time.
The research was performed at the University of Pennsylvania School of Engineering and Applied Science, receiving support from the National Science Foundation (DMR-2309043 and CAREER Awards 2339278 and 2047271) and the National Institutes of Health, including the National Institute of General Medical Sciences (R35GM133380), the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK132296), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K25HD097288 and R21HD112663).
