August 7, 2014

expert reaction to neurons derived from human skin stem cells being regrown in rats with spinal cord injuries

A paper in Neuron reported that induced pluripotent stem cells (iPSCs) derived from skin cells taken from an 86-year-old man were grafted into rats with spinal cord injuries, leading to regrowth of neurons.

Prof Chris Mason, Professor of Regenerative Medicine, UCL, said:

“Which cell type is best to restore function following spinal cord injury is an open question. So too is the timing of their administration to the patient. Is it technically advantageous to transplant cells in the early phase of injury (1-2 weeks) when the spinal cord is still ‘bruised’ and before scar tissue appears, or later? The damage is different and so too will be the therapy. Early is akin to a house just having caught fire, whereas later is more like a burnt-out building. One urgently needs water, the other a major rebuild – the appropriate remedies are different, so too with injuries to the spinal cord.

“Neural stem cells produced from donor tissues have already shown potential in animal models to reconnect the brain to the body following spinal cord injury. But these cells are from donors (not self) and therefore have the potential for rejection and need life-long immunosuppression, which has side effects. The big advantage of using donor cells is that they would be readily available off the shelf, just like any other drug, and therefore can be given immediately to the injured patient. Paul Lu has converted the equivalent of patient’s own skin cells into neural stem cells and seen promising results when administered in an animal model at 2 weeks after injury. If this translates into humans, the upside is no need for immunosuppression, but the downside is that the current cell conversion process takes months – much too long for the same early administration to patients. It is no use pouring water on a burnt-out building.

“The present state of the science for early spinal cord treatment is still very early with donor cells that potentially need life-long immunosuppression therapy, and patient’s own cells that currently take too long to manufacture. This dilemma is precisely why scientists must keep investigating all the different cell types until additional major breakthroughs enable progression to the clinic. This paper moves the field forward, however, there is still much to do.”

Prof Geoff Raisman, Chair of Neural Regeneration, Institute of Neurology, UCL, said:

“The central finding is that adult human skin cells retain, even at advanced age, the ability to be converted into stem cells which behave in the same way as has previously been shown for embryonic nervous system cells.  Thus, when transplanted into damaged areas of the rat spinal cord, the reprogrammed cells grow very long fibres and make connections.

“In terms of spinal cord repair, the transplants do not appear to restore functions lost as a result of fibres severed by the spinal injury.  There is a concern whether in the long term infiltrating the entire brain and spinal cord with such exuberant and uncontrolled growth of fibres may have deleterious effects.”

Dr Dusko Ilic, Reader in Stem Cell Science, King’s College London, said:

“This is an interesting study that highlights the power of reprogramming technology and induced pluripotent stem cells. It did not come as a surprise that iPSC-derived neural stem cells, grafted into injured spinal cord and stimulated by local microenvironment, can differentiate to the desirable cell type and integrate with the host neurons. In previous studies with human embryonic stem cell (hESC)-derived oligodendrocyte precursors, the results were not as encouraging. The difference occurred because the grafted cells were different – more potent neural stem cells here vs. less potent oligodendrocyte progenitors in previous studies – not because of the origin of parental cells (hESC vs. iPSC).

“However, the fact that grafted neural cells gave a rise to immature neurons extending their processes through nearly the entire animal nervous system and still continue to divide and grow, should serve as a warning that we have to be very cautious in using stem cell-based therapies in humans. We still do not know enough and once when the cells are grafted into the recipient, we have no control over them.”

Prof Daniel Brison, Professor of Clinical Embryology and Stem Cell biology, University of Manchester, said:

“This paper is important as it brings the use of human pluripotent stem cells for clinical therapeutic use another step closer.  However there is still much work to be done to ensure that induced pluripotent stem cells are safe for clinical use and to ensure that any treatments are effective and cost-effective.”

‘Long-distance axonal growth from human induced pluripotent stem cells after spinal cord injury’ by Paul Lu et al. published in Neuron on Thursday 7 August 2014.

Declared interests

None declared