Issue: October 2004
October 01, 2004
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Stem cell repair of meniscus, cartilage studied

Injectable stem cell preparation that regenerates the meniscus could be on the market soon; cartilage repair research seems promising.

Issue: October 2004
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In Summary

Repairing meniscus, cartilage:

  • At Genzyme, stem cells injected into damaged joint
  • Chondrogen regenerated meniscus in animal model
  • Cells targeted to damaged cartilage made normal cartilage
  • Stem cells cultured, transplanted into cartilage defects

Unlike bone, cartilage has no capacity to regenerate itself and meniscal tissue has limited capacity for self-repair. Despite those challenges, however, researchers have made a great deal of progress in developing ways to use stem cells to repair these tissues.

Researchers at Osiris Therapeutics Inc. have developed Chondrogen, an injectable preparation of stem cells suspended in hyaluronan that has demonstrated the ability to regenerate a meniscus in six weeks in a large animal model.

“This is an injection directly into the knee space, so it’s not at all invasive. What we found is not only does it in fact regenerate a meniscus, it can regenerate a meniscus from nothing,” C. Randal Mills, PhD, told Orthopedics Today. Mills is president and chief executive officer of Osiris.

“Another benefit that we’ve seen of the use of Chondrogen is a dramatic reduction in subsequent osteoarthritis and osteophyte formation. There’s very good chondroprotection that takes place with this product.”

Mills said the animal and safety trials were done and that the company has submitted the data to the Food and Drug Administration. He believes they should be able to start human trials for Chondrogen “quite soon.”

Cartilage repair

In addition to meniscal regeneration, there is also a great deal of research underway examining the potential of stem cells for cartilage repair. Researchers at Genzyme, the developer of Carticel, are considering a variety of approaches, said Ross Tubo, PhD, vice president of orthopedic research and stem cell biology.

“Since stem cells have been shown to home in to sites of tissue injury in nonorthopedic models, one approach that we are investigating is to simply inject the stem cells into the damaged joint and allow the cells to find their way to the sites of damage and facilitate repair,” Tubo said.

photo
This engineered cartilage tissue was transplanted into artificial cartilage defects of miniswine knee joints. Results show promise for enhancing cartilage healing.

COURTESY OF CHING-CHUAN JIANG

The company is also investigating a variety of extracellular matrices containing bioactive factors for their ability to effectively deliver the stem cells and then direct their differentiation into the appropriate repair tissue type (ie, articular cartilage or meniscal fibrocartilage). The bioactive factor would most likely come from the transforming growth factor beta superfamily that includes bone morphogenetic proteins.

Arnold Caplan, PhD, and his colleague James Dennis, PhD, are working on a method of targeting cells to precise locations by putting “addresses” on them. This was done by determining which antibodies to components of deep cartilage matrix were optimal for binding stem cells to damaged cartilage, said Caplan, director of the Skeletal Research Center at Case Western Reserve University.

“We then took a section of damaged rabbit cartilage and put it in a tissue culture plate and incubated it for a few weeks. We found that the human chondrocytes that were sitting on that damaged cartilage actually start making beautiful, normal cartilage. … So now we know that the cells that we targeted to that damaged cartilage are not only specifically binding, but they are also making real functional cartilage matrix.”

Ching-Chuan Jiang, MD, PhD, and colleagues at the National Taiwan University Hospital in Taipei, Taiwan, have developed a method for extracting stem cells from the proximal femurs of patients undergoing total hip replacement.

Jiang’s team cultured stem cells on a 3 mm by 3 mm nonwoven polyglycolic acid scaffold until they grew into cartilage tissue. This engineered tissue was then transplanted into cartilage defects in miniswine knee joints. “The results are promising in enhancing the healing of cartilage,” Jiang told Orthopedics Today.