As you point out in your News story 'Stem cells ready for prime time' (Nature 457, 516 2009), the recent approval by the US Food and Drug Administration (FDA) of the first clinical trial to use derivatives of human embryonic stem (ES) cells is an important development. But the indication, namely spinal-cord injury, raises concerns and important caveats.
First, the choice of a body area that is not simple to access is surprising in the context of what is meant to be primarily a safety trial. The field needs reliable information with regard to possible immune rejection of the transplanted cells and their potential to de-differentiate in situ after implantation.
Second, the benefits are not likely to be easy to assess, given what has been experienced with animal models of spinal-cord lesion. Difficulties in reproducing the lesion and in assessing both the damage and regrowth of axons after experimental manipulations have made results hard to interpret. It is generally agreed that cut axons cannot readily regrow in adult mammals, but it is not clear why. Damage caused by inflammatory cells, scar formation and decreased intrinsic growth drive of adult neurons, as well as the inhibitory effect of myelin in the central nervous system, may all play a part.
The trial approved by the FDA consists of injecting oligodendrocyte precursors into the spinal cord of patients soon after injury, implying that a lack of such precursors may be the key issue. Oligodendrocyte precursors do seem to myelinate axons after lesion in rodents (H. S. Keirstead et al. J. Neurosci. 25, 4694–4705; 2005). However, the results still need to be interpreted in the context of what goes wrong after spinal-cord injury, including the possibility that axonal elongation may actually be impaired by oligodendrocyte-derived products.
Nonetheless, the generation of virtually pure populations of oligodendrocyte precursors is impressive, one of very few cases of cellular homogeneity of a differentiated cell type generated from ES cells (G. I. Nistor et al. Glia 49, 385–396; 2005). This achievement opens the way to studying the impact of mutations after reprogramming somatic cells from patients, and drug screening in a relevant cellular context.
Given the controversy over the use of human ES cells in some countries, it is to be hoped that the triumphant announcement of the approval of this clinical trial will not prove to be a prime-time setback. Regenerative medicine using human ES cells is an exciting prospect, but the field still needs time to mature. The primary concern of scientists involved in stem-cell research is not to satisfy the short-term expectations of analysts and investors, but to improve public health with the help of innovative, safe treatments.
Contributions may be submitted to email@example.com and will be edited.
About this article
Cite this article
Barde, Y. Caution urged in trial of stem cells to treat spinal-cord injury. Nature 458, 29 (2009). https://doi.org/10.1038/458029a
Nature Reviews Rheumatology (2014)