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.
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.”
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.
For more info, go to http://www.keyence.com/BIDMC