Stem-Cell Therapeutics for Spinal Injury Treatment

Researchers at the University of Colorado (Denver, USA), in collaboration with researchers at the University of Rochester (NY, USA) used signal molecules, known to be involved in the generation of embryonic astrocytes during spinal cord development, to make pure cultures of two different types of astrocytes from glial-restricted precursor (GRP) cells. The two astrocyte-derived cells, however, had remarkably different effects on the spinal repair process. GRP-derived astrocytes (GDAs) derived from GRPs treated with bone morphogenetic protein-4 (BMP-4), were able to promote robust axon regeneration and functional recovery when transplanted into rat spinal cord injuries. In contrast, transplantation of GDAs generated by exposure to the ciliary neurotrophic factor (CNTF), the other major signaling pathway involved in astrogenesis, resulted in failure of axon regeneration and functional recovery. Moreover, the transplantation of the GDACNTF cells promoted the onset of mechanical allodynia and thermal hyperalgesia at two weeks after injury, an effect that persisted through five weeks post-injury. Delayed onset of similar neuropathic pain was also caused by transplantation of undifferentiated GRPs. However, rats transplanted with GDAsBMP did not exhibit pain syndromes. The research teams considered the distinction between the effects of GDAsBMP, GDACNTF, and undifferentiated GRP cells a breakthrough that might change the way stem cell technologies are used to repair spinal cord injuries. The study was published in the September 19, 2008, edition of the Journal of Biology, an open access publication of BioMed Central (BMC).

"It has long been a concern that therapies that promote growth of nerve fibers in the injured spinal cord would also cause sprouting of pain circuits,” said lead author Stephen Davies, Ph.D., an associate professor of neurosurgery at the University of Colorado. "However, by using GDAsBMP to repair spinal cord injuries we can have all the gains without the pain, while these other cell types appear to provide the opposite – pain but no gain.”

Controlling the development of stem cells immediately before transplanting them into injured spinal cords is essential, since doctors cannot rely on the injured tissues of the body to create the right types of cells from naïve stem cells. The GRP cell, which is central to this effort, and the techniques for turning them into astrocytes were discovered by Doctors Margot Mayer-Proschel, Mark Noble, and Christoph Proschel of the department of biomedical genetics at the University of Rochester.

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