Transplanted Neurons Restore Function In Rats After Stroke

The neurons originated in an embryonal cancer cell line that was treated with retinoic acid in a process to differentiate the cells and to render them benign.

Significantly, when the human neuronal cells were frozen and then thawed prior to transplantation, they proved equally as effective as fresh cells in easing the symptoms of stroke in rats. Furthermore, the tumor-derived cells did not revert to abnormal tissue growth after transplantation into the brains of rats.

"This suggests that human neuronal cell transplantation may be a useful alternative to fetal tissue in treating strokes and other neurodegenerative disorders," says Paul R. Sanberg, PhD, professor and director of neurosurgical research at USF and senior author on the study. "The grafts' resistance to the effects of cryopreservation is rather remarkable. Frozen fetal brain cells do not survive long after they are thawed."

Experimental transplantation using fetal brain cells has been successful in a small number of patients with Parkinson's disease, but the potential for widespread use of fetal tissue is limited, partly because of difficulties associated with preservation.

"The clinical potential is that a readily available supply of cryopreserved human neuronal cells, made under controlled conditions and stored frozen, could be used as replacement therapy to reverse the deficits of stroke," notes Virginia M.-Y. Lee, PhD, a professor of pathology and laboratory medicine at Penn and a coauthor on the study.

Lee and Penn colleague John Q. Trojanowski, MD, PhD, also a professor of pathology and laboratory medicine and study coauthor, developed a procedure to isolate and purify the NT2N neurons from a culture of mixed cells removed from a cancerous human tumor. Treatment with retinoic acid altered the cells so that they became noncancerous and differentiated to take on the characteristics of neurons.

The process has been patented by the University of Pennsylvania Medical Center and licensed to Layton BioScience Inc. of Atherton, California, which provided the cells used in the USF study. Layton BioScience is developing the cells, known commercially as hNT-Neurons, for the treatment of several neurological disorders.

In the experiments, the USF researchers implanted the hNT-Neurons into the brains of rats. In rats receiving immunosuppressive drugs to control graft rejection, function was restored and maintained for more than six months following transplantation.

"The hNT-Neurons were just as beneficial as fetal brain cells alone in improving movement and behavioral recovery," observes Sanberg.

The University of South Florida Health Sciences Center has graduated 2,000 doctors, 3,300 nurses, and 1,000 public health professionals. In 1996-1997, 350 faculty-physicians in the College of Medicine handled 470,000 patient visits, HSC sponsored research topped $50 million, and USF physicians provided $20 million worth of uncompensated care.