Powerful imaging technique for studying bone marrow in mouse models

Powerful imaging technique for studying bone marrow in mouse models

Scientists at Indiana University School of Medicine have developed a powerful new imaging technique to study bone marrow in mouse models. By overcoming important challenges unique to imaging this complex tissue, this advance could support future drug development and therapies for bone marrow-related diseases, including cancers, autoimmune diseases, and musculoskeletal disorders.

The new method was made possible by the multiplex imaging tool Phenocycler 2.0, which allowed researchers to visualize a dataset of cellular markers within intact bone marrow tissues of mice. The results were recently published inLeukemia.

Bone marrow is difficult to examine because it is gelatinous and enclosed in hard bone. Because bone marrow plays an important role in the formation of blood and immune cells and harbors valuable stem cells, our unique imaging approach provides a useful tool for a variety of research applications. “

Sonali Karnik, PhD, associate research professor of orthopedic surgery at the IU School of Medicine and co-lead author of the study

Traditional tools such as flow cytometry and standard fluorescence imaging are considered the most established methods for tissue analysis. However, flow cytometry requires complex tissue perturbation to examine and quantify cell populations, and standard fluorescence imaging is limited to detecting only three cellular markers at a time. In contrast, the new methodology allowed researchers to visualize 25 different cellular markers in intact bone marrow tissue without disruption, providing a more comprehensive view of the bone marrow to improve understanding of disease behavior and the development of more effective treatments.

While the tool has previously been used to examine organs such as the spleen and kidney, the IU Cooperative Center of Excellence's 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 such as 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 method, and the team is now working to expand the marker panel to include additional features such as bones, nerves, muscles, 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.

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