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Biologics Feature

Source: Wikimedia Commons and Alexandru Darida

Genes + Scaffold Key to Stem Cell Activity

Biloine W. Young • Fri, March 7th, 2014

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To get stem cells to repair tissue has, up to the present, required the application of large amounts of growth factor proteins which signal the stem cells to differentiate into cartilage and other tissues. A major difficulty has been delivering these growth factors to the stem cells once they are implanted on a structure into the body. Charles Gersbach, Ph.D., an assistant professor of biomedical engineering at Duke University and an expert in gene therapy, spent years developing biodegradable synthetic scaffolding that mimics the mechanical properties of cartilage.

As Farshid Guilak, Ph.D., director of orthopedic research at Duke University Medical Center, explains, “There's a limited amount of growth factor that you can put into the scaffolding, and once it's released, it's all gone. We needed a method for long-term delivery of growth factors, and that's where the gene therapy comes in.” By introducing new genes and using viruses to deliver gene therapy to the stem cells they have induced the stem cells to make the necessary growth factors all on their own.

What they have is Gersbach’s polymer structure for growing cartilage that includes gene therapy vectors to induce the stem cells, themselves, to produce the growth factors they need. The new technique, called biomaterial-mediated gene delivery, is shown to produce cartilage at least as good biochemically and biomechanically as if the growth factors were introduced in the laboratory.

By combining a synthetic scaffolding material with gene delivery techniques, researchers at Duke University believe that they are getting closer to being able to generate replacement cartilage where it is needed in the body. The results show that the technique works and that the resulting composite material is at least as good biochemically and biomechanically as if the growth factors were introduced in the laboratory, according to the researchers. The researchers say that the resulting material acts like a computer—the scaffold provides the hardware and the virus provides the software that programs the stem cells to produce the desired tissue.

"We want the new cartilage to form in and around the synthetic scaffold at a rate that can match or exceed the scaffold's degradation, " said Jonathan Brunger, a graduate student. "So while the stem cells are making new tissue (in the body), the scaffold can withstand the load of the joint. In the ideal case, one would eventually end up with a viable cartilage tissue substitute replacing the synthetic material."

While this study focuses on cartilage regeneration, Guilak says that the technique could be applied to many kinds of tissues, especially orthopedic tissues such as tendons, ligaments and bones. And because the platform comes ready to use with any stem cell, it presents an important step toward commercialization.

"One of the advantages of our method is getting rid of the growth factor delivery, which is expensive and unstable, and replacing it with scaffolding functionalized with the viral gene carrier, " said Gersbach. "The virus-laden scaffolding could be mass-produced and just sitting in a clinic ready to go. We hope this gets us one step closer to a translatable product." The study appears online in the Proceedings of the National Academy of Sciences.

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One Response to “Genes + Scaffold Key to Stem Cell Activity”

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