New technique to deliver gene therapy to soft-tissue tumors

Using new research and technology that shows bone marrow-derived mesenchymal stem cells (MSCs) will engraft at the site of a tumor and contribute to the growth of stromal fibroblasts (the healthy tissue surrounding a tumor), researchers at the Columbus Children’s Research Institute, on the campus of the Columbus Children’s Hospital, have now found a way to efficiently genetically modify MSCs using a modified Adeno-Associated Virus (AAV) vector system and deliver therapeutic genes to the site of a tumor. The procedure proved to be over a thousand times more efficient than other vector systems.

The research, the first of its kind, was presented Sunday, May 2, 2004, at the Pediatric Academic Societies’ (PAS) Annual Meeting in San Francisco.

“We know that transplanted MSCs will specifically seek out tumors and continue to develop and grow in the tumor environment,” said Jeffrey S. Bartlett, Ph.D., principal investigator in the Gene Therapy Center at Columbus Children’s Research Institute (CCRI) on the campus of Columbus Children’s Hospital. “Now, we’ve found a way to efficiently genetically modify these cells and to use them to specifically transport gene-based therapies to pediatric tumors. This new system may overcome one of the greatest shortcomings of gene therapy, which has always been the delivery of the therapy itself.” Previous research and anti-cancer therapies have focused on targeting tumor cells themselves, or in some instances, the blood supply that “feeds” the tumor.

This study is one in a growing number of studies aimed at targeting the supportive tumor stroma, the healthy tissue surrounding a tumor.

To develop a system that would efficiently deliver and express a therapeutic gene in MSCs, Dr. Bartlett’s team began with vectors based on AAV because of their ability to promote long-term gene expression in the absence of integration.

The researchers began by isolating MSCs from human bone marrow. These cells are easy to work with, explained Dr. Bartlett, and can be easily expanded in culture. The modified AAV vector they generated was used to deliver genes into these cells, which were then transplanted into models of pediatric soft-tissue sarcomas, common forms of solid tumors in children. The genetically engineered stem cells proved to be an effective delivery system for gene therapy in these tumors.

Columbus Children’s Hospital ranks among the top 10 in National Institutes of Health research awards and grants to freestanding children’s hospitals in the country. With nearly 500,000 patient visits each year, Children’s Hospital is a 112-year-old pediatric healthcare network treating newborns through age 21. In 2003, the Columbus Children’s Research Institute conducted more than 300 research projects and is the home of Centers of Emphasis encompassing gene therapy; molecular and human genetics; vaccines and immunity; childhood cancer; cell and vascular biology; developmental pharmacology and toxicology; injury research and policy; biopathology; microbial pathogenesis; and biobehavioral health.

Pediatric Clinical Trials International (PCTI), a site management organization affiliated with the hospital, also coordinated more than 50 clinical trials. In addition to having one of the largest ambulatory programs in the country, Children’s offers specialty programs and services.

More than 75,000 consumers receive health and wellness education each year and affiliation agreements with nearly 100 institutions allow more than 1,700 students and 500 residents to receive training at Children’s annually. More information on Children’s Hospital of Columbus is available by calling (614) 722-KIDS (5437) or through the hospital’s Web site at


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