St. Jude researchers prove mesenchymal cell infusions enhance effects of bone marrow transplant for children with brittle bone disease

St. Jude Children's Research Hospital (ALSAC)
Tuesday, 25 June 2002

First human study to show therapeutic potential of mesenchymal cells

Treatment with bone marrow mesenchymal cells, specialized bone-making cells, has the potential to enhance the therapeutic effects of bone marrow transplantation in patients with osteogenesis imperfecta (OI), also known as brittle bone disease. Researchers at St. Jude Children's Research Hospital published these findings in the June 25 issue of the journal Proceedings of the National Academy of Sciences.

Mesenchymal cells are bone-marrow cells that have the ability to form body tissues such as bone, cartilage, muscle and fat.

"This is the first human trial to clearly show the therapeutic potential of mesenchymal cells and represents a significant step forward in the development of cellular therapies," said Edwin Horwitz, M.D., Ph.D., a member of the department of Hematology-Oncology at St. Jude and the lead investigator for the research.

For the study, infusions of gene-marked, donor-marrow derived mesenchymal cells were used to treat five children, ranging in age from 2 years, 10 months to 4 years, 9 months, who had previously undergone standard bone marrow transplantation for severe OI. The mesenchymal cells were harvested from the bone marrow of patients' transplant donors.

The patients received an initial infusion of mesenchymal cells 18-34 months after bone marrow transplant. After a second infusion, a few weeks later, all of the patients show engraftment in one or more sites, including bone, skin and bone marrow. Additionally, the children experienced an acceleration of growth during the first six months post-infusion. The growth rates ranged from 60 percent to 94 percent of the predicted growth for children unaffected by OI. The patients had experienced growth rates of 0 percent to 40 percent in the six months prior to the infusions.

The use of bone marrow transplantation as a treatment for OI was pioneered at St. Jude and previously reported in Nature Medicine in 1999.

"For kids with OI, our study represents hope for an improved treatment program and someday a cure," Horwitz said. "For all people with diseases of mesenchymal tissue such as bone, cartilage or muscle, our study represents the potential for new cellular therapy that may improve our general treatment strategies."

The treatment methodology used in the study is based on the research of Dr. Darwin Prockop, M.D., Ph.D., who investigated the genetic mutations that cause OI. Prockop is a faculty member at the Tulane Center for Gene Therapy in New Orleans, La.

OI is a genetic disorder characterized by bones that break easily, often from little or no apparent cause. The disease can be mild to severe and affects between 20,000 and 50,000 Americans. OI is caused by a genetic defect that affects the production of collagen, the major protein of the body's connective tissue. Patients with OI have either less collagen or a poorer quality of collagen than healthy individuals, leading to weak bones that fracture easily. There is not yet a cure for OI. Current treatment is directed toward preventing or controlling the symptoms, maximizing independent mobility and developing optimal bone mass and muscle strength.

For more information, or to contact St. Jude Children's Research Hospital (ALSAC), see their website at: www.stjude.org