Bone Marrow-Derived Stem Cells Used for Potential Treatment of Gliomas

Newswise — More than 40,000 Americans each year are diagnosed with brain tumors, according to the National Institute of Neurological Disorders and Stroke. About half of those are primary, the others are metastatic. A recent study on the treatment of gliomas, "Bone Marrow-Derived Stem Cells in the Treatment of Human Gliomas," will be presented from 10:30 to 10:45 a.m. on Monday, May 3, 2004, during the 72nd Annual Meeting of the American Association of Neurological Surgeons in Orlando, Florida. The study will be presented by Frederick F. Lang, MD. Authors of the study include neurosurgeons Frederick F. Lang, MD, Akira Nakamizo, MD, and specialists in bone marrow transplant Frank C. Marini, PhD and Michael Andreeff, MD, PhD. The study was a collaboration of the Department of Neurosurgery and the Department of Marrow and Blood Transplantation at MD Anderson Cancer Center.

The authors note that there is currently no effective treatment for gliobastoma multiforme (GBM), the most common malignant brain tumor. Patients diagnosed with GBM usually survive less than one year.

"This poor outcome is due in part to the inability to deliver the necessary therapeutic agents throughout the tumor," said Frederick F. Lang, MD, a coauthor of the study. "We understand that achieving widespread distribution of therapeutic agents throughout the glioma could greatly improve brain tumor therapy."

Several laboratories have demonstrated the potential for neural stem cells to function as delivery vehicles for brain tumor therapy. However, historically there have been logistical and ethical problems with neural stem cells related to their isolation and expansion during treatment. Due to the significant limitations associated with isolating human neural stem cells, to date only neural stem cells from rats have been used in experimental settings.

"The problems associated with neural stem cells led us to ask whether other types of stem cells that are more readily accessible and clinically applicable may be used as vehicles for delivering therapeutic agents to brain tumors," said Dr. Lang.

Authors learned that human bone marrow-derived stem cells could be used for clinical application because they are easily obtained from patients and because it is possible to perform autologous transplantation. Of the different types of stems cells that exist with bone marrow, human mesenchymal stem cells (hMSCs) are especially beneficial for clinical use because they are easy to isolate and expand in culture, and they can be genetically manipulated.

The authors hypothesized that tumors could provide a proper environment for hMSCs. In this study, which utilized an intracranial model of gliomas, the authors evaluated whether or not brain tumors could support engraftment of hMSCs. The authors isolated and expanded the bone marrow samples obtained from normal human donors. Next, they implanted gliomas into the frontal lobes of mice and injected hMSCs into the carotid artery. When the authors examined the tumors seven days after delivering the stem cells, they found the stem cells exclusively within the tumor but not in other areas of the brain. This result demonstrated that hMSCs have a tropism for human gliomas. The authors noted that growth factors might mediate this tropism.

To investigate whether hMSCs could deliver therapy to gliomas, the authors engineered the stem cells to secrete interferon-b, a powerful anti-glioma agent. Treatment with the engineered stem cells given systemically, significantly extended the survival of animals with established intracranial gliomas.

The authors concluded that it is possible for bone-marrow derived hMSCs to serve as effective vehicles for delivering therapeutic agents to brain tumors. They look forward to future studies analyzing the clinical application of this type of stem cell therapy for brain tumors.

Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 6,500 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system including the spinal column, spinal cord, brain and peripheral nerves.