Good method but bad results for stem cell, spinal cord study shows


A study published in the Journal of Neurosurgery Spine shows that the neural stem sphere (NSS) method can be successfully used to derive astrocytes from induced pluripotent stem cells (iPSCs), but it has also found that transplanting astrocytes into the spinal cord does not repair spinal cord injury.

Koichi Hayashi, Department of Orthopaedic surgery, Chiba University, Graduate School of Medicine, Chiba, Japan, and his co-authors hypothesised that as the NSS method was successfully used to obtain dopamine cells from embryonic stem cells and transplant them into monkeys with Parkinson’s disease with a resultant improvement in motor function, the same process could be used to derive astrocytes from iPSCs. Although initially astrocytes were believed to be harmful after spinal cord injury because they reproduce rapidly and form a glial scar, recent studies have indicated that they may be beneficial. Hayashi et al reported: “Widespread infiltration of inflammatory cells results in severe motor deficits after spinal cord injury. Reactive astrocytes can surround inflammatory tissue and prevent inflammatory spread.” They therefore investigated whether transplantation of astrocytes, from mice iPSCs, into rats with spinal cord injuries could improve motor recovery.


Using the NSS method, the investigators found that they could: “Propagate neural stem cells in this fashion and then use cryopreservation. Neural stem cells were successfully differentiated into astrocytes, neurons, and oligodenrocytes.” The astrocytes were then injected into rats with contusion-based spinal cord injuries three and seven days after the injury was induced. The rats, along with a control group of rats with spinal cord injuries that had been injected with DMED (at three or seven days after the injury), were assessed for locomotion recovery and sensitivity for eight weeks.


After eight weeks, the transplanted cells had survived and had changed their character to GFAP-negative cells. Despite this finding, the rats with the transplanted cells did not have significantly improved motor function compared with the control group. There was no significant different between the two groups in the Basso-Beattie-Bresnahan Open-Field Locomotor score (p=0.99 for the difference between the 3- day groups; p=0.115 for the difference between the 7-day groups). Other sensory motor tests, such as the SCANET and the inclined-plane test, did not find any differences between the transplant group and the control group.


However although all rats with spinal cord injury were found to have greater sensitivity to mechanical stimulus than normal rats (who did not have a spinal cord injury), the 3-day astrocyte group showed a lower threshold for mechanical stimulus than the 3-day control rats (p=0.013).


Hayashi et al reported: “Greater sensitivity to mechanical stimulus is mainly caused by reactive astrocytes perhaps through the secretion of diffusible chemical transmitters, which may augment primary afferent neuronal signalling or sensitise second-order neurons in the spinal cord.” There were no differences in the sensitivity thresholds between the 7-day astrocyte group and the 7-day control group.


Hayashi et al concluded their findings by saying that transplanting a single-cell for spinal cord injury, such as astrocytes, was insufficient to improve functional recovery. They added: “A critical aspect of regenerative medicine is guaranteeing the safety of the patient. In that regard, we suggest that the NSS method, which is quite simple and efficient, could be used with confidence.”