INDIANAPOLIS — Indiana University School of Medicine scientists have developed a powerful new imaging technique to study bone marrow in mouse models. By overcoming key challenges unique to imaging this complex tissue, this advancement could support future drug development and therapies for conditions involving bone marrow, including cancers, autoimmune diseases and musculoskeletal disorders.
The new method was made possible by the multiplex imaging tool Phenocycler 2.0, which enabled researchers to visualize a record number of cellular markers within intact bone marrow tissue from mice. The findings were recently published in Leukemia .
"Bone marrow is difficult to study because it is gelatinous and encased in hard bone," said Sonali Karnik, PhD , assistant research professor of orthopedic surgery at the IU School of Medicine and co-lead author of the study. "Since bone marrow plays an important role in blood and immune cell formation and houses valuable stem cells, our unique imaging approach offers a useful tool for a variety of research applications."
Traditional tools like flow cytometry and standard fluorescence imaging are considered the most established methods for tissue analysis. However, flow cytometry requires disrupting complex tissues to study and quantify cell populations, and standard fluorescent imaging is limited to detecting only three cellular markers at a time. In contrast, the new methodology allowed the researchers to visualize 25 different cellular markers in intact bone marrow tissue without disruption, providing a more comprehensive view of the bone marrow to enhance the understanding of disease behaviors and the development of more effective treatments.
While the tool has previously been used to study organs like the spleen and kidney, the IU Cooperative Center of Excellence in Hematology team is the first to successfully apply it to mouse bone marrow.
"Because mouse models are widely used to study human diseases, this technique offers a promising new method for investigating a range of conditions like autoimmune diseases, leukemia and other disorders involving bone marrow," said Reuben Kapur, PhD , a co-senior author on the study, director of the IU School of Medicine's Herman B Wells Center for Pediatric Research and co-director of the IU Cooperative Center of Excellence in Hematology.
The IU Innovation and Commercialization Office has filed a provisional patent for the new imaging methodology, and the team is now working to expand the marker panel to include additional features such as bone, nerves, muscle and more immune and signaling cell types.
Additional IU study authors include Connor Gulbronson, Paige C. Jordan, Rahul Kanumuri, Baskar Ramdas, Ramesh Kumar, Melissa L. Hartman, Izza Khurram, Drew M. Brown, Karen E. Pollok, Pratibha Singh and Melissa A. Kacena.
This research was supported by funding from the National Institutes of Health.
About the Indiana University School of Medicine
The IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability. According to the Blue Ridge Institute for Medical Research, the IU School of Medicine ranks No. 13 in 2024 National Institutes of Health funding among all public medical schools in the country.