University of Medicine and Dentistry of New Jersey --UMDNJ-- Researchers Convert Bone Marrow Stem Cells to Neurons.

Business Editors, Health/Medical Writers

NEWARK, N.J.--(BW HealthWire)--Aug. 14, 2000

Researchers at the University of Medicine and Dentistry of New Jersey (UMDNJ), in research funded by the Christopher Reeve Paralysis Foundation (CRPF), have developed the first successful procedure to convert cultured bone marrow stem cells exclusively into nerve cells.

This critical advance now provides an abundant and accessible cellular reservoir to potentially treat a variety of neurological diseases, including spinal cord injury, stroke, brain trauma, and degenerative diseases such as Parkinson's, Alzheimer's and Lou Gehrig's diseases.

The results of the study, led by Dr. Ira Black, chair of the Department of Neurosciences at UMDNJ-Robert Wood Johnson Medical School and his colleague Dale Woodbury, are published in the August 15th issue of The Journal of Neuroscience Research. The work was performed in collaboration with Darwin Prockop and Emily Schwarz of MCP Hahneman University.

"Now that we have been able to differentiate human bone marrow stromal stem cells into neurons, it creates the exciting possibility in the future for the treatment of neurological diseases," said Dr. Black.

"The possibilities for spinal cord and brain repair suggested by this study are quite profound. The Christopher Reeve Paralysis Foundation (CRPF) has committed considerable energy and resources to its Research Consortium on Spinal Cord Injury and we believe that the exciting results of Dr. Black's research underscore the wisdom of that strategy," said Susan Howley, CRPF Executive Vice President and Director of Research.

The research incorporates a number of important advances:

-- The use of bone marrow cells provides a safe procedure,

eliminating the high risk operation of obtaining stem cells

from deep within the brain.

-- Success with adult stem cells obviates the need for fetal

tissue, eliminating a number of ethical concerns.

-- The use of an individual's own (autologous) bone marrow cells

eliminates the introduction of foreign cells and the need for

toxic immunosuppressive drugs to avoid rejection.

-- Rapid cellular growth and self-renewal in culture provides a

virtually limitless source of cells, and eliminates the need

for immortalization and tumor-forming potential.

In addition, Dr. Black said, from a scientific point of view, the work suggests that presumed fixed gene mechanisms that determine cell fate can be changed by environmental signals.

"We are most excited about the future potential this finding holds for patients with spinal paralysis, stroke and degenerative brain diseases," Dr. Black said. "Research currently being conductedon rats with spinal paralysis suggests that stem cell transplants can encourage return of function.

"We know that neural stem cells migrate to areas in the brain that have been damaged. It appears that the cells can assume regional functions and actually improve function of the damaged systems."

For this study, the research team harvested the human and rat bone marrow stem cells and placed them in culture where they were treated with the protocol developed specifically to induce conversion to neurons.

The researchers used time lapse photography to study the differentiation process. "Frankly, we were startled that the conversion took place so rapidly. Using our procedure, stem cells converted to neurons within minutes to hours and even began forming connectional networks with other neurons."

The scientists also identified specific neuronal gene products in the cells, confirming the conversion to neurons.

"As we improved the protocol, we obtained 80 percent conversion to neurons and rapid reproduction of the cells," Dr. Black said.

The team also performed a clonal analysis to determine whether each bone marrow stem cell had the capacity to generate neurons, or whether only a small a sub-population participated. "We found that each cell gave rise to neurons, providing a vast reservoir of source material."

Dr. Black and his team are already in the midst of the next stage of this research, which involves transplantation of these cells into the brain and spinal cord of laboratory animals.