The biotech company Geron Corporation is working with human embryonic stem cells (hESC) converted into oligodendroglial progenitor cells for use in treating spinal cord injuries in rats and mice.
Menlo Park, CA – November 13, 2003 – Geron Corporation (Nasdaq: GERN) today announced the presentation of results demonstrating that the transplant of cells differentiated from human embryonic stem cells (hESCs) can result in functional improvement in animals with spinal cord injuries. This work provides proof of concept of the efficacy of hESC-based therapies in spinal cord injury.
In two presentations at the Society for Neurosciences Annual Meeting in New Orleans, Dr. Hans Keirstead and his colleagues from the University of California at Irvine detailed studies demonstrating that when hESC-derived oligodendroglial progenitors were transplanted into rats that had received a thoracic spinal cord contusion injury, statistically significant improvements in the ambulatory activity of the rats could be observed approximately one month later. In these blinded studies, animals showed evidence of improved weight-bearing capacity, paw placement, tail elevation and toe clearance activity compared to injured untreated animals. Control animals that received transplants of human fibroblasts instead of oligodendroglial progenitors showed little, if any improvement.
“These results are exciting. They show that cells derived from hESCs can have therapeutic efficacy in a model of human disease,” stated Jane S. Lebkowski, Ph.D., Geron’s vice president of regenerative medicine.
In these studies, the cells were transplanted directly into the spinal cord lesions seven days after injury. Dr. Keirstead found evidence of both increased oligodendrocyte-mediated myelination and some neural sprouting upstream of the lesion in the test animals. These observations were further supported by additional transplant studies from Dr. Keirstead’s lab in which the oligodendroglial progenitors were implanted into the spinal cord of Shiverer mice, a mutant mouse that is deficient in myelin basic protein and hence lacks normal neuronal myelination. In those mice the researchers observed evidence of oligodendrocyte-mediated remyelination of nerve cell axons. No evidence of tumor formation from the transplanted cells or other adverse events was observed in any of these studies.
In a third presentation at the meeting, Dr. Keirstead and his colleagues presented data showing how hESCs can be differentiated in tissue culture to oligodendroglial progenitors, the precursors of oligodendrocytes. Oligodendrocytes are specialized neural cells that produce myelin, the protective sheath that insulates the axons of nerve cells allowing normal nerve impulse conduction. Oligodendrocytes also produce a variety of neurotropic factors which can induce the sprouting of nerve cells. In a spinal cord contusion injury, neurons that are spared during the initial injury can be demyelinated during the subsequent inflammatory response. Such demyelination can lead to decreased nerve conduction velocity and eventual death of the “denuded” axons, producing impaired sensory and motor function.
“This work demonstrates the versatility of hESCs and their potential utility for broad-based cellular therapeutics,” added Thomas B. Okarma, Ph.D., M.D., Geron’s president and chief executive officer. “In these studies, oligodendroglial progenitors were produced multiple times from the same human embryonic stem cell line over a period of months. The success of these studies and potential economies from large batch production of oligodendroglial progenitors from hESCs supports development of this potential product for the treatment of patients with acute spinal cord injury.”Geron is now initiating formal preclinical safety and efficacy studies and is planning for scaled-up production of the cells for potential use in human clinical trials.
Suppose that within 5 or 10 years a Geron has a therapy derived from hESC ready for market for those suffering from spinal cord injuries. Suppose that therapy will help restore some spinal cord function with some degree of restoration of control and feeling in the lower body. The opponents of the use of hESC for therapeutic purposes are going to be faced with a much more difficult political position as the larger public has to weigh ethical concerns voiced by hESC therapy opponents against the very concrete ability to allow children and adults to arise from wheelchairs. My guess is that the hESC opponents will fail to keep hESC therapies off the market since they have failed to get a complete ban on the development of hESC therapies. Once a single therapy that provides a benefit as dramatic as helping crippled people walk again reaches the market the political opposition to hESC-based therapies will wither.
Geron is working on the basic nuts and bolts of being able to deliver therapies based on hESC as demonstrated by a report of their progress on developing better techniques for growing hESC in culture.
Menlo Park, CA – November 19, 2003 – Geron Corporation (Nasdaq: GERN) today announced the development of a defined, serum-free culture system for the propagation of human embryonic stem cells (hESCs). This new culture system relies solely on completely defined components for hESC growth, facilitating safe and scalable expansion of these cells for cell-based therapeutics.
In a presentation at the 2003 annual meeting of the American Institute of Chemical Engineers in San Francisco, Geron presented studies demonstrating that hESCs could be expanded in a culture medium that contains only human-sourced proteins and defined recombinant growth factors. Using these defined conditions, hESCs could be propagated for at least 120 days in culture while maintaining normal morphology, doubling time, and expression of a panel of markers characteristic of hESCs. Moreover, hESCs propagated under these conditions continued to be pluripotent, differentiating into cells representative of endoderm, mesoderm, and ectoderm, the three cell lineages of the human body.
This work extends Geron’s previous development of feeder-free growth conditions for hESCs. Geron had earlier developed protocols to culture hESCs in the absence of direct contact with feeder cells by using extracellular matrix proteins and cell-free media that had been previously conditioned by feeder cells. “This new development allows the replacement of conditioned medium with a fully defined medium that contains only human-sourced proteins and purified growth factors,” stated Jane S. Lebkowski, Ph.D., Geron’s vice president of regenerative medicine. “This advance greatly facilitates the scalable production of the cells while essentially eliminating the risk of contamination by non-human infectious agents in the culture process for undifferentiated cells.”
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