Toward Speeding Wound Healing

Efforts to mitigate patient discomfort during and after medical treatments has focused on making procedures less invasive. For instance, laparoscopic surgery, using specially designed tools which allow much smaller incisions, has been used when possible to greatly reduce recovery and healing times. Now physicians are developing a therapy that may one day cut healing time by helping the body to heal wounds faster.

Zhenghong Lee is a Case Western Reserve University and Center for Stem Cell and Regenerative Medicine researcher on the project. He and his colleagues, Stanton Gerson, James Dennis and Jeffrey J. Auletta at the Center for Stem Cell and Regenerative Medicine, are testing whether a therapy using stem cells can aid healing. “[Stem cells] have great potential in so many things – therapeutic repair, such as bone fracture, cartilage damage, and even some of the heart problems,” Lee says.

Stem cells can be obtained from many different sources. Perhaps the most well known are embryonic stem cells, which come from human embryos. However, Lee and his colleagues are using a type of stem cell donated by adult volunteers and categorized as the Mesenchymal Stem Cells (MSCs), which were derived from adult bone marrow, a far less controversial source.

The researchers have modified the MSC by inserting extra genes into the cells’ DNA. One of these genes, called firefly luciferase, is from the North American firefly, commonly known as the lightning bug. It’s the gene that allows fireflies to light up on a warm summer evening. In mice, this gene causes the MSC to produce a gentle glow that can be detected by a sensitive camera.

Two other genes have also been inserted in the cells’ DNA. A second reporter gene makes the MSC visible in a petri dish, so that the researchers can identify which stem cells to use as a drug therapy. The last gene will produce a protein (enzyme) that binds to a radiopharmaceutical, which will eventually allow researchers to use nuclear medical imaging to monitor how MSC function inside the body. Lee says the researchers are currently using firefly luciferase to track MSC as they travel inside the bodies of mice.

The researchers can see where these cells go thanks to a new optical camera procured and tested by Jefferson Lab’s Detector and Imaging Group, headed by Stan Majewski. The camera was recently added to an imaging system the group had already built and had been used by CWRU researchers in studies of a gene therapy for cystic fibrosis. For that study, the system was bi-modal, with the ability to capture nuclear medical images and x-ray images. The group upgraded the system to a tri-modal unit by adding a very sensitive optical camera for the MSC study.

Carl Zorn, a member of the Detector and Imaging Group, says finding just the right camera was a challenge. “The main problem is that the amount of light you’re talking about is very small. So you need a very sensitive detector for light,” he explains.

The group decided to procure a camera that uses charged-coupled device (CCD) technology for the system. “They use a solid-state detector called a CCD, which is the same thing you see in digital cameras. The only difference is that these CCDs are actually cooled to a very low temperature,” Zorn says. Cooling the camera produces sharper pictures by eliminating the natural electronic noise produced by the CCD itself.

Once a camera had been purchased, Zorn tested the camera by taking pictures of ordinary ivy leaves, which give off an extremely faint glow in the minutes after they’ve been exposed to sunlight. “The initial test was just to take a leaf, just an ordinary leaf from outside. Bring it inside, close the door on the dark box, because the picture has to be taken in total darkness. Take the picture, and lo and behold, you see the glow from the leaf itself – the leaf actually fluoresces.”

Zorn optimized the new camera and then sent it to CWRU for installation. “My job was to select it, and when it came here, test it. And essentially teach them how to use it. The rest was up to them,” he says.

Lee says the system is doing its job, as evidenced by the false-color images of the glowing MSC in the sleeping mice. Now that the CWRU team has shown that the new tri-modal unit can image the cells, the researchers are planning the next phase of the study. They hope the therapy marked by these glowing cells will home in on sites of injury in the mouse and lend a hand in wound healing. Lee says the next step is to track whether the MSC do just that in injured mice.

“Some people say the stem cells will differentiate into the cells for healing. But we believe it’s probably not the main mechanism for wound healing. It’s not much differentiation, but more like modulation — they release something that facilitates the repairing or healing process,” he says, ”But there is a great deal of debate.” Lee expects preliminary research results from this next step sometime in the next year.

Research Update
Lee and his colleagues’ research regarding cystic fibrosis gene therapy is on the fast track: researchers are now conducting clinical trials on humans after the mouse version of gene therapy imaging experiments for cystic fibrosis. Read more about this research and the bi-modal camera it used.

From Jefferson Lab


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