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Combining cell biology and bioengineering, researchers work to create 'mini kidney' for accurate testing

Upstate Medical University cell biologist Mira Krendel, PhD, working with Syracuse University bioengineer Pranav Soman, PhD, will use a nearly $500,000 grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) over the next two years to create a 3D printed miniature model of the kidney system.

This project could lead to better treatments for kidney-related conditions, improving the lives of patients with chronic kidney disease (CKD). According to the CDC, about 37 million adults in the United States are estimated to have CKD, and most cases go undiagnosed. This work could also help decrease the need for animal testing, while potentially providing more accurate results when testing potential drugs and treatments.

This research project focuses on understanding and recreating the filtration process that happens in the kidneys, specifically in tiny structures called glomeruli. Problems with this process can lead to chronic kidney disease, often requiring lifelong treatments like dialysis.

“Researchers have been trying for a while to create different models where you can grow something that looks like glomeruli in culture and then test how it's affected by medications, toxins, or different genetic or environmental conditions,” explains Krendel. “The problem is current models don’t have the same complicated shape.”

Krendel, a professor of cell and developmental biology, has spent her career using experimental techniques to better understand kidney function and disease.

The team proposes to use advanced techniques, including laser technology and 3D printing, to create a miniature model of the kidney's filtration system. They call it the Glomerular-BOwman’s CapSule system on the chip (GOAL-chip). This model mimics the intricate network of blood vessels in the kidney and allows researchers to study how cells called podocytes and endothelial cells function in this environment.

Soman is 3D printing the structures in his lab at SU’ BioInspired Institute. He works as an associate professor of biomedical and chemical engineering in Syracuse University’s College of Engineering and Computer Science. “What my group has is a completely new technology that allows me to basically carve out complicated shapes.” He explains that while most 3-D printing is “additive”; adding layer-by-layer to create a structure, his team combines this with a “subtractive” approach, allowing them to create extremely complex structures.

While the structure created may be complicated, simplicity is the goal. “Can you make this so that any lab anywhere in the United States could use it?” asks Krendel. This goal aligns with Soman’s engineering work.

“I started a company a few years ago to basically democratize the use of complex tissue-on-chips by life-science researchers like Krendel,” he explained. “Ultimately, we would hope that we could print these structures, send them to someone else, tell them how to add cells, and they could use them to answer their own questions.”

This project also complies with the recent Food and Drug Administration’s Modernization Act 2.0, which empowers researchers to employ innovative non-animal methods. Researchers hope that innovations like organ-on-a-chip models can provide more accurate testing and trial results than animal testing.

“There are some differences between species which come along that researchers can't really predict,”  Soman said. “If I am able to recreate all those key components on a chip with human cells, drug screening will be much more precise.”

Krendel and Soman have been working on this project for almost a decade. “We've been accumulating more and more data on what these chips can do in the lab,” Krendel said. “I think it finally got to the point where the reviewers looked and said, ‘Oh yeah, now we think it can be done’.”

Krendel credits this project to collaboration. “You can't really get this to work without having a bioengineer, but you also cannot get it to work without a biologist. I think that's a good example where being close to Syracuse University’s Biomaterials Institute and interacting with people in other areas of research is important.”

Read more about the Krendel Lab and their work here:

https://www.upstate.edu/cdb/research/krendelm/index.php

Read more about the Soman Lab here:

https://psoman.expressions.syr.edu/

Read more about the FDA Modernization Act 2.0 and its potential impact on scientific research here-

https://www.science.org/content/resource/new-path-new-drugs-finding-alternatives-to-animal-testing

 

Caption: Pranav Soman, PhD, of Syracuse University, and Mira Krendel, PhD, of Upstate Medical University, are collaborating on research for treating chronic kidney disease.

 

 

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