In a World Full of 3D Models, Researchers Build a New One for Leukemia
A Wilmot Cancer Institute scientist published data that show a new microchip-like device that his lab developed can reliably model changes in the bone marrow as leukemia takes root and spreads.
Ben Frisch, Ph.D., assistant professor of Pathology and Laboratory Medicine and Biomedical Engineering at the University of Rochester, and colleagues have been building what is known as a modular bone-marrow-on-chip to enhance the investigation of leukemia stem cells. The tiny device recapitulates the entire human bone marrow microenvironment and its complex network of cellular and molecular components involved in blood cancers.
Similar tissue-chip systems have been developed by others, but they lack two key features contained in Frisch’s product: osteoblast cells, which are crucial to fuel leukemia, and a readily available platform.
The fact that Frisch’s 3D model has been published in Frontiers in Bioengineering and Biotechnology and is not a one-off fabrication will allow others in the field to adopt a similar approach using the available microfluidics system, he said.
Azmeer Sharipol, a second-year graduate student in Biomedical Engineering at UR, is taking charge of the project in Frisch’s lab and is first author of the study. Another fundamental contributor is Maggie Lesch, now a first-year graduate student, who kicked off the project during her time as a technician in the lab.
Often when scientists study leukemia in the lab, Sharipol noted, they are limited to human or mouse cells and not able to see the bigger picture of how disease develops. “We hope that by modeling the bone marrow niche, we will gain a better understanding and be able to discover potential therapeutic targets.”
Ultimately, researchers plan to use the chip to quickly evaluate how human leukemia cells respond to drug treatment. At this point, Frisch and Sharipol have shown proof of principle that the pre-clinical 3D model is a cost-effective tool for rigorous analysis of bone marrow cells in the laboratory.
The American Society of Bone and Mineral Research (ASBMR) notified Sharipol that he will receive a Young Investigator Award at its annual meeting in September 2022, and he’s has been invited to make an oral presentation.
“The most exciting part of the project is learning from leukemia research experts who are at the forefront of their field at Wilmot and also getting the perspectives of clinicians who work closely with patients,” Sharipol said. “I’m able to explore my curiosity and apply my tissue-engineering skills while still focusing on a dire pathological problem.”
Leukemia has an overall five-year survival rate of less than 30 percent and often afflicts older people. The 27-county Rochester region from which Wilmot draws patients has more adults older than age 65 than most similar regions across the U.S. Aging blood systems, bone marrow failure, and other health issues place older adults at a greater risk of cancer.
Studying the complexities of the bone marrow and how blood cancers arise is a longtime research strength at Wilmot. Several investigators in Wilmot’s Cancer Microenvironment program are looking at how to interrupt the process in different ways.