Manipulating embryo-derived stem cells before transplanting them may hold the key to optimizing stem cell technologies for repairing spinal cord injuries in humans, according to research published in the Journal of Biology. They say it may lead to cell based therapies for victims of paralysis to recover the use of their bodies without the risk of transplant induced pain syndromes.
Dr. Stephen Davies, Associate Professor of Neurosurgery at the University of Colorado Denver School of Medicine, reported that, in collaboration with researchers at the University of Rochester, his research team has transplanted two types of the major support cells of the brain and spinal cord, cells called astrocytes. These two types of astrocytes, which are both made from the same embryo-derived stem cell-like precursor cell, have remarkably different effects on the spinal repair process.
Using signal molecules known to be involved in the generation of embryonic astrocytes during spinal cord development, the researchers were able to make pure cultures of two different types of astrocytes from the GRP cells. The glial-restricted precursor (GRP) cell, which is central to this effort, and the techniques for turning them into astrocytes were discovered by Drs Margot Mayer-Proschel, Mark Noble and Christoph Proschel at University of Rochester.
When Dr. Davies and his team transplanted these two types of astrocytes into the injured spinal cord, they had dramatically different effects. One type of astrocyte called GDAsBMP was remarkably effective at promoting nerve regeneration and recovery of limb motion when transplanted into spinal cord injuries. However, the other type of astrocyte cell generated called GDAsCNTF, not only failed to promote nerve fiber regeneration or functional recovery but also caused neuropathic pain, a severe side effect that was not seen in rats treated with GDAsBMP.
“To our knowledge, this is the first time that two distinct sub-types of astrocyte support cells generated from a common stem cell-like precursor cell have been shown to have robustly different effects when transplanted into the injured adult nervous system,” co-author Dr. Mayer-Proschel said.
Transplantation of the stem cell-like precursor cells without first turning them into astrocytes, also caused pain syndromes and no spinal repair. Davies said “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. 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.” The research teams considered the distinction between the effects of GDAsBMP, GDAsCNTF and GRP cells a “breakthrough” that might change the way stem cell technologies are used to repair spinal cord injuries.
Controlling the development of stem cells immediately before transplanting them into injured spinal cords is essential because doctors cannot rely on the injured tissues of the body to create the right types of cells from “naïve” stem cells.
Co-author Mark Noble said “These studies are particularly exciting in addressing two of the most significant challenges to the field of stem cell medicine – defining the optimal cell for tissue repair and identifying means by which inadequately characterized approaches may actually cause harm.’ To that end, the researchers are developing a safe, efficient and cost-effective way to make human GDAsBMP with an eye toward testing this new stem cell technology in humans.
This research was supported by the New York State Spinal Injury Research Board, the National Institute of Neurological Disorders and Stroke, the Lone Star Paralysis Foundation, the Christopher and Dana Reeve Foundation and donations from private individuals.
Article: Jeannette E Davies, Christoph Proschel, Ningzhe Zhang, Mark Noble, Margot Mayer-Proschel and Stephen J.A. Davies, 'Transplanted astrocytes derived from BMP or CNTF treated glial restricted precursors have opposite effects on recovery and allodynia after spinal cord injury', Journal of Biology