BIDMC: Digital microscope Helping Hearts

Researchers at Harvard University get a better look at heart disease and other ailments with fluorescent microscopy from KEYENCE.The genetic disorder Noonan syndrome (NS) causes a host of problems in humans. Growth and musculoskeletal abnormalities, distinctive facial features, issues with the lymphatic system, bruising and bleeding are all associated characteristics of NS, but the most serious complication is congenital heart disease, which manifests itself through a narrowing of the pulmonary valve or through weakening of the heart muscle itself.

Fabrice Jaffré, an Instructor in Dr. Maria Kontaridis´ laboratory at Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, is working on elucidating the mechanisms associated with causing this disorder. He and others in the Kontaridis lab study the cardiac defects in NS patients, as well as those associated with a rarer, allelic variant disorder called Noonan Syndrome with Multiple Lentigines. formerly known as LEOPARD syndrome.

"By understanding how abnormal signaling pathways lead to heart defects in these patients, we can begin to assess how specific and targeted drug or gene therapies can work to ameliorate the disease" Jaffré says.

One possible treatment for these and other genetic diseases may come through the use of inducible pluripotent stem cells (iPSCs). As Jaffré explains, these cells are cultivated from the patient´s own body-typically from the skin or blood-and de-differentiated into iPSCs, which have the potential to then re-differentiate and become virtually any type of cell in the human body, including nerve, bone, and muscle; in Jaffré ´s case, they are become cardiomyocytes, the cells responsible for making the heartbeat.

Jaffré says that the analysis of these cells would be more difficult if not for a fairly recent addition to the Kontaridis lab´s equipment list, one that greatly expands its capabilities: a KEYENCE BZ-X700 All-in-One Fluorescence Microscope.

"I might place a bunch of cardiac cells in a specimen dish and use antibodies to perform immunofluorescence," he says. "The KEYENCE helps you to identify many different proteins that are expressed in cardiomyocytes with high resolution. It also does automatic measurement of cell size, and cell number in each sample. These tasks would be more difficult or at least more time consuming without it."

The BZ-X700 is KEYENCE´s publication-quality imaging and analysis solution for researchers throughout the life sciences. It uses a high-sensitivity CCD camera to capture low-noise color or monochrome images, even when fluorescent signals are weak. The integrated software provides a range of features such as image stitching, 3D measurement, optical sectioning and more, and does so with an intuitive interface that requires very little training to operate.

"We get excellent resolution in both still images and video," Jaffré says. "It´s also quite user friendly. Even if you´re unfamiliar with microscopy, you´ll be able to operate the device easily."

Aside from automatic cell counts, area and linear measurement, and other types of specimen analyses, the KEYENCE is used by the lab for time-lapse motion tracking, a function particularly valuable to Jaffré. "Cardiomyocytes form monolayers, or sheets of cells that beat together, just like in the human heart. We use the KEYENCE to measure contractility, and the number of beats per minute at the cellular level. By analyzing the differences between the cardiomyocytes of NS patients and those of control subjects, we´re able to identify defects in the patient-derived cells."

Jaffré´s also pleased with some of the other features the KEYENCE BZ-X700 brings to the lab, such as the flexibility to use a variety of well plates and dishes, automatic measurement of large sample sizes, and image stitching. "We can do most anything we want for microscopy with the KEYENCE," he says.

iPSC research such as this may one day provide individualized therapy for treating common patient ailments, Jaffré points out. For example, it may be possible to extract cellular material from a heart attack victim and use it to generate iPSCs that can then be reintroduced to repair those that were damaged by the event.

Jaffre is close to releasing a paper on his research, one that will include images obtained from the KEYENCE. For lab director Dr. Maria Kontaridis, an Associate Professor of Medicine at Harvard Medical School and the interim Director of the Basic Cardiovascular Research Program at Beth Israel Deaconess Medical Center, this is always welcome news. "We purchased the KEYENCE nearly two years ago," she says. The images are stellar and its capabilities have proved helpful to everyone in the lab. For instance, the ability to show real-time hypertrophy in individual cardiomyocytes has been invaluable to Fabrice, and we have additional postdoctoral fellows in the lab who are also working on understanding the mechanisms associated with end stage heart failure. In this case, the KEYENCE is used to automatically quantity the percentage of fibrosis in each of the mouse heart tissue samples, something we also utilized in a recently published manuscript with the Journal of Clinical Investigation. We´ve also recommended the KEYENCE to other institutions here at the medical school complex as well. Overall, we´re very happy with its capabilities."

KEYENCE has steadily grown since 1974 to become an innovative leader in the development and manufacturing of automation equipment worldwide. Our products consist of automation sensors, static eliminators, barcode readers, measuring instruments, vision systems, laser markers, and digital microscopes.

Keyence Corporation of America

1100 North Arlington Heights Rd. Suite 210, Itasca, IL 60143

Phone: 1-888

KEYENCE (539-3623)

Fax: 1-201-930-0099

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