Monthly Archives: August 2012

Nanoscale scaffolds, stem cells show promise in cartilage repair

 Johns Hopkins tissue engineers have used tiny artificial fiber scaffolds thousands of times smaller than a human hair to help coax stem cells into developing into cartilage, the shock-absorbing lining of elbows and knees that often wears thin from injury or age.

Reporting online June 4 in the Proceedings of the National Academy of Sciences, investigators say they have produced an important component of cartilage in both laboratory and animal models. While the findings are still years away from use in people, the researchers say the results hold promise for devising new techniques to help the millions who endure joint pain.

“Joint pain affects the quality of life of millions of people. Rather than just patching the problem with short-term fixes, like surgical procedures such as microfracture, we’re building a temporary template that mimics the cartilage cell’s natural environment, and taking advantage of Nature’s signals to biologically repair cartilage damage,” said Jennifer Elisseeff, the Jules Stein Professor of Ophthalmology and director of the Translational Tissue Engineering Center at the Johns Hopkins University School of Medicine.

Unlike skin, cartilage can’t repair itself when damaged. For the last decade, Elisseeff’s team has been trying to better understand the development and growth of cartilage cells called chondrocytes, while also trying to build scaffolding that mimics the cartilage cell environment and generates new cartilage tissue. This environment is a three-dimensional mix of protein fibers and gel that provides support to connective tissue throughout the body, as well as physical and biological cues for cells to grow and differentiate.

In the laboratory, the researchers created a nanofiber-based network using a process called electrospinning, which entails shooting a polymer stream onto a charged platform, and added chondroitin sulfate—a compound commonly found in many joint supplements—to serve as a growth trigger. After characterizing the fibers, they made a number of different scaffolds from either spun polymer or spun polymer plus chondroitin. They then used goat bone marrow–derived stem cells (a widely used model) and seeded them in various scaffolds to see how stem cells responded to the material.

Elisseeff and her team watched the cells grow and found that compared to cells growing without scaffold, these cells developed into more voluminous, cartilage-like tissue.

“The nanofibers provided a platform where a larger volume of tissue could be produced,” said Elisseeff, adding that three-dimensional nanofiber scaffolds were more useful than the more common nanofiber sheets for studying cartilage defects in humans.

The investigators then tested their system in an animal model. They implanted the nanofiber scaffolds into damaged cartilage in the knees of rats, and compared the results to damaged cartilage in knees left alone.

They found that the use of the nanofiber scaffolds improved tissue development and repair as measured by the production of collagen, a component of cartilage. The nanofiber scaffolds resulted in greater production of a more durable type of collagen, which is usually lacking in surgically repaired cartilage tissue. In rats, for example, they found that the limbs with damaged cartilage treated with nanofiber scaffolds generated a higher percentage of the more durable collagen (type 2) than those damaged areas that were left untreated.

“Whereas scaffolds are generally pretty good at regenerating cartilage protein components in cartilage repair, there is often a lot of scar tissue–related type 1 collagen produced, which isn’t as strong,” Elisseeff said. “We found that our system generated more type 2 collagen, which ensures that cartilage lasts longer.

“Creating a nanofiber network that enables us to more equally distribute cells and more closely mirror the actual cartilage extracellular environment are important advances in our work and in the field. These results are very promising,” she said.

Other authors were Jeannine M. Coburn, Matthew Gibson, Sean Monagle and Zachary Patterson, all of Johns Hopkins.

The research was supported by grants from the National Institutes of Health.

Source: Audrey Huang, Johns Hopkins Medicine, The JHU Gazette


New Canadian research uses stem cells as possible treatment for arthritis

A Toronto research team hopes to make hip and knee replacements a thing of the past as it explores the growth of new human cartilage using stem cells.

With an estimated four million Canadians suffering from arthritis, and that number expected to grow to seven million by 2031, doctors are hoping to use the stem cells to treat the deterioration of cartilage in joints. “Although hip and knee replacements are a great operation, they improve patients’ lives in terms of pain, quality and function, they’re not your own joint,” Dr. Nizar Mahomed told CTV’s Canada AM on Friday. “They don’t last forever and they bring risks and limitations.”

Mahomed, an orthopedic surgeon at Toronto’s Western Hospital, said 45,000 hip and knee replacement surgeries are preformed in Canada each year. Many of the surgeries are to treat the damage left by arthritis, which he said is caused by aging, obesity and injuries.  

“The incident of arthritis increases with age, so as our population ages the prevalence of arthritis is going to continue to increase.”

Mahomed and his colleagues are one of the first research teams in the world that have been able to grow human cartilage.

The team is now embarking on the next stage of the study, which will see the new tissue used in animals.

“If we actually make it work in animals then one day we’ll be able to bring it back into patients,” said Mahomed.

He added that stem cells hold much hope for medicine in the future as studies are looking at using the cells to regenerate cardiac tissue and in the treatment of nerve and spinal cord injuries.

Mahomed said he hopes within five to 10 years the new technology can be used in human patients while putting an end to joint replacement surgeries.

“We’re working to put ourselves out of business,” he quipped.