New cartilage can be grown directly in the patient's body
NanoNewsNet based on materials from Duke University: Gene Therapy Might Grow Replacement Tissue Inside the BodyBy combining synthetic substrate material with viral vectors for gene delivery, researchers from Duke University have come close to the possibility of growing new cartilage directly in the patient's body, where it is needed.
Tissue repair using stem cells, as a rule, requires the use of large amounts of protein growth factors, which is very expensive and difficult to do if the cells are already implanted in the body. However, scientists at Duke University have found a way around this limitation: by genetically modifying stem cells, they forced them to produce growth factors on their own.
By embedding viruses used to deliver the necessary genes to stem cells into a synthetic material that serves as a substrate for the growth of cartilage tissue, they obtained a material that can be compared to a computer. The substrate in such a computer is iron, and the virus is software that programs stem cells to create the right tissue.
The results of the study by American scientists are published online in the journal Proceedings of the National Academy of Sciences (Brunger et al., Scaffold-mediated lentiviral transduction for functional tissue engineering of cartage).
Farshid Guilak, PhD, who directs orthopedic research at Duke University Medical Center, has been developing biodegradable synthetic substrates that mimic the mechanical properties of cartilage for many years. However, along the way, he and other biomedical researchers have encountered many problems, one of which is to force stem cells to form cartilage inside and around the substrate, especially after it is implanted into the body of a living being.
The traditional approach is to introduce proteins – growth factors– that signal stem cells to differentiate into cartilage. As soon as the process begins to go in full swing, the growing cartilage can be implanted where it is needed.
"But the main limitation in the engineering of tissue substitutes has always been the difficulty in delivering growth factors to stem cells when they are implanted in the body," explains Dr. Gilak, a professor in the Department of biomedical Engineering at Duke University. "Only a limited amount of growth factor can be placed in the substrate, and as soon as it is released, it breaks down. We need a method of long-term delivery of growth factors, and here gene therapy comes to our aid."
Associate Professor of Biomedical Engineering and expert in the field of gene therapy Charles Gersbach, PhD, to whom Professor Gilak asked for help, suggested introducing new genes into stem cells so that they themselves produce the necessary growth factors.
However, conventional gene therapy methods are complex and difficult to translate into a strategy based on which a commercial product can be created.
This type of gene therapy, as a rule, requires taking stem cells, modifying them with a virus that inserts new genes into their genome, cultivating genetically modified stem cells until they reach a critical mass, applying them to a synthetic cartilage substrate and, finally, implanting this entire structure into the body.
"There are a lot of problems with this process, and one of them is that there are too many steps in it," explains Dr. Gersbach. "Therefore, we turned to a technique I had previously developed, in which viruses delivering new genes are fixed on the surface of a material."
In the new study, Gersbach's technique – called biomaterial-mediated gene delivery (biomaterial-mediated gene delivery) – is used to induce the production of protein growth factors by stem cells placed on a synthetic cartilage substrate of Gilak. The results show that this method works and that the resulting composite material is at least as good, biochemically and biomechanically, as if growth factors were introduced in the laboratory.
A section of engineering tissue showing cartilage (red),
filling the space between the bundles of polymer fibers (white).
(Charles Gersbach and Farshid Guilak, Duke University)
"We want new cartilage to form inside and around the synthetic substrate at a rate that is comparable to or exceeds the rate of decomposition of the substrate," explains graduate student Jonathan Brunger, who participated in the development and testing of the new method in the laboratories of both scientists. "Then, while the stem cells will create a new tissue (in the body), the substrate will take over the load on the joint. Ideally, it is possible to eventually obtain viable new cartilage tissue replacing synthetic material."
Although this study focuses on cartilage regeneration, according to Gilak and Gersbach, this method can be applied to many types of tissues, especially orthopedic tissues such as tendons, ligaments and bones. And since the new platform is ready for use with any stem cells, it represents an important step towards commercialization of their method.
"One of the advantages of our method is that we got rid of the delivery of the growth factor, which is expensive and unstable, and replaced it with a substrate functionalized by a viral vector," Dr. Gersbach sums up. "A virus-loaded substrate can become a mass-produced product and is always available in the clinic, ready for use."
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