Oligodendrocyte Progenitors Show Functional Improvements in Spinal Cord Injuries
May 11, 2005 - 6:53:38 PM
Geron Corporation (Nasdaq:GERN) announced today the publication of studies showing that oligodendrocyte progenitors, differentiated from human embryonic stem cells (hESCs), produce functional improvements in rats with spinal cord injuries. These studies provide proof of concept for the therapeutic potential of differentiated hESCs in the treatment of neurological disorders such as spinal cord injury.
In the May 11 issue of the Journal of Neuroscience, Dr. Hans Keirstead and his colleagues from the Reeve Irvine Research Center at the University of California, Irvine published studies demonstrating that hESC-derived oligodendroglial progenitor cells (OPCs) could be delivered to the injured spinal cord in rats and resulted in functional improvement in locomotion as well as histological evidence of spinal cord repair.
Oligodendrocytes are normal cellular components of the central nervous system that wrap and insulate neurons in a process known as myelination. Such myelin wrapping enables efficient electrical transmission in neurons in the central nervous system. After spinal cord injury and the subsequent inflammatory response, native oligodendrocytes at the injury site die, leading to myelin destruction and consequent impaired electrical conduction even in those neurons that may have survived the initial injury. Demyelination of neurons leads to both sensory and motor deficits.
hESC-derived OPCs transplanted directly into the rat spinal cord injury survived and migrated appropriately both upstream and downstream from the lesion. Rats transplanted seven days after injury showed improved walking ability compared to animals receiving a control transplant. The OPC-treated animals showed improved hindlimb-forelimb coordination and weight bearing capacity, increased stride length, and better paw placement compared to control-treated animals. Such improvements in locomotor function were not observed when injured animals were treated ten months after injury, likely due to extensive scar formation which developed at the injury site in the months prior to OPC transplant. The studies document the potential therapeutic use of hESC-derived OPCs in acute spinal cord injury.
Microscopic examination of the spinal cords of OPC-treated animals showed evidence of spinal cord repair. Transplantation of the OPCs seven days after injury led to remyelination or "reinsulation" of demyelinated axons at the lesion site. Using labeled OPCs, the transplanted cells were visually observed to produce branches which wrapped the rat neurons. These results provide direct evidence for the structural tissue reparative function of these hESC-derived cells.
"Numerous studies have addressed the impact of demyelination in the pathophysiology of spinal cord injury," stated Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer. "The work published today demonstrates the potential for human embryonic stem cell-based therapies to restore normal physiological function by means of repairing tissue lost to injury or disease. We are currently engaged in preclinical development studies to ultimately enable testing of these cells in humans."
These studies in Dr. Keirstead's laboratory were conducted with support from Geron Corporation, a University of California Discovery Grant and the Roman Reed Spinal Cord Injury Fund of California.
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