Bone Morphogenetic Protein-4 aka BMP-4

Muscle Stem Cells Transformed Into Cartilage
By Ed Edelson
HealthDay Reporter
Mon Jan 30, 5:02 PM ET

MONDAY, Jan. 30 (HealthDay News) -- Researchers say they have turned adult muscle stem cells into cartilage, and used them in animals to heal the kind of damage caused by arthritis.

That is potentially good news for the many people who now face joint-replacement surgery because there is no available technique to repair cartilage damage from osteoarthritis, the wear-and-tear condition that afflicts many older people.

The transformed cells have successfully replaced damaged cartilage in rats for as long as 24 weeks, much longer than has been reported in studies using other methods, according to a report in the February issue of Arthritis & Rheumatism.

Experiments aimed at extending the benefit to 48 weeks are in the planning stage, with an eye out for human trials, said study leader Johnny Huard, director of the Growth and Development Laboratory at the Children's Hospital of Pittsburgh.

"Over the years, a lot of people have tried to use cells to repair cartilage, which doesn't repair by itself," said Huard. "So far, nobody has been able to repair cartilage with those cells. In this study, we found a population of stem cells in skeletal muscle that we give a boost with a protein so they differentiate into cartilage cells. Then we can repair cartilage damage in our animal model."

Discovery of the protein that does the transformation was one of those happy accidents, Huard added. It is bone morphogenetic protein-4 (BMP-4), so named because it has been used for years to make bone cells. A look at the cells thus treated in a different project showed they resembled cartilage cells, and that observation led to the new breed of cartilage cells.

If all works out as hoped, Huard said, treatment of damaged cartilage would start with a biopsy to obtain muscle stem cells from the person needing the treatment. "That is the nice thing about it, because by taking muscle cells from you, we bypass the immune reaction against foreign cells, he said.

The cells would then be grown in culture to create patches for the damaged cartilage.
The experiments described in the journal report used 36 young rats, all with damaged cartilage, who were divided into three groups. One of those groups got muscle stem cells genetically engineered to produce BMP-4, another got plain muscle stem cells, the third just got a coating of glue.

Studies over the next 24 weeks showed repair in the BMP-4 mice, and not in the others.
It's not possible to say when human trials of the transformed cells might start, Huard said. But human trials are underway to test the safety of muscle stem cells against a different condition, bladder dysfunction, which causes embarrassing leakage, he said.

An accompanying editorial by Dr. Mary B. Goldring, of the New England Baptist Bone and Joint Institute, said the study "provides proof-of-principle for performing muscle-derived stem cell implantation in cartilage of humans, since 12-week-old rats are considered to be young adults," and that "further work is warranted" to see if the method works in humans.

More information
More on cartilage and what can go wrong with it is available from the National Library of Medicine.

Primary source: Arthritis & RheumatismSource reference: Kuroda R et al. Cartilage Repair Using Bone Morphogenetic Protein 4 and Muscle-Derived Stem Cells. Arthritis & Rheumatism 2006: 54(2); 433-442.