Transplanted astrocytes repair spinal cord damage in rat

A couple of weeks ago I discussed the launch of two clinical trials of brain machine interfaces designed to allow quadriplegic patients to control a newly designed prosthetic limb, during which I mentioned that scientists are also studying techniques that attempt to repair damage to spinal cords using stem cells.  Several approaches have already shown promise in animal studies, for example oligodendrocyte progenitor cells that are derived from human embryonic stem cells that we have discussed on Speaking of Research before, and olfactory ensheathing cells that continuously regenerate nerve cells in the lining of our noses. Research on the ability of these cells to repair spinal cord damage has depended on animal research, indeed olfactory ensheathing cells were originally identified in rats by Professor Geoffrey Raisman before being confirmed to exist in humans too.

This week a team of scientists working at the University of Rochester and the University of Colorado School of Medicine led by Professor Chris Pröschel have shown in rats that another type of cell can repair spinal cord damage, publishing the results of their study in the open access journal PLoS One.

Sprague-Dawley rats are a very useful model for spinal cord repair. Image courtesy of Understanding Animal Research

Astrocytes are star-shaped glial cells that support nerve cells, and have an important role in the regulation of the transmission of electrical impulses within the brain.  They are also involved in the repair of damaged nerve tissue, prompting scientists to study whether transplanting them at the sites of spinal cord injury can repair damage and restore function, but the results to date have been disappointing.

What Prof. Pröschel’s team showed was that there are functional differences between two distinct subtypes of human astrocytes derived from a common fetal glial precursor population in the ability to promote repair of the injured adult central nervous system, confirming an observation they had previously made is studies of rat glial derived cells (1). When injected at the injury site in rats whose spinal cord had been severed just below the neck on one side, Human fetal glial progenitor cells (hGPCs) which had been treated with bone morphogenetic protein (BMP), a growth factor that plays an important role in regulating the development of many tissues, protected nerve cells and promoted their regrowth, and promoted a substantial improvement locomotor function 28 days after injury and transplantation, as determined by measuring the ability of rats to walk along a horizontal ladder. Conversely hGPCs which had not been treated, or had been treated with the ciliary neurotrophic factor, a growth factor previously identified as playing an important role in astrocyte development, did not protect nerve cells or promote locomotor recovery, despite the observation that they migrated to the same locations within the site of injury as the BMP treated cells.

Earlier studies of the ability of astrocytes to repair spinal cord damage had used mixed astrocyte population, so it is not surprising that they did not see such striking benefits.

Prof. Pröschel’s team also found that robust functional recovery in the rat was only obtained when hGPCs were pre-differentiated with BMP to produce astrocytes before transplantation, a result in close agreement with their earlier studies of which examined the ability of glial progenitor cells to repair spinal cord damage (1).

Commenting on these exciting results in a report in the Denver Post Prof. Pröschel noted that:

What’s really striking is the robustness of the effect…Scientists have claimed repair of spinal-cord injuries in rats before, but the benefits have been variable and rarely as strong as what we’ve seen with our transplants”

His colleague Stephen Davies indicates that the team is hoping to begin clinical trials of this therapy soon, perhaps even within the next two years:

Now the challenge is how rapidly can we translate these discoveries from the lab for use in humans…We are working hard to translate this technology in the next one to two years. It’s difficult to predict”

His caution is fully justified, regulators are very cautious about giving permission for trials of stem cell based therapies to go ahead, and before doing so they may well demand that further animal studies are undertaken to assess the longer-term safety of hGPC-derived astrocyte transplantation. It is also worth noting that in this study the astrocytes were transplanted on the same day as injury, a time to treatment that will be very difficult to achieve in the clinic.  Before starting clinical trials it would be very advisable to determine how effective the treatment is at a series of time points up to 14 days after injury, in order to determine the length of the time window within which the treament must be started.

Nevertheless, this is a very promising study that, in addition to being important and interesting in its own right, adds to the growing body of evidence supporting the potential of stem cell therapy to repair spinal cord damage and prevent paralysis.

Paul Browne

1)    Davies JE, Proschel C, Zhang N, Noble M, Mayer-Proschel M, et al. (2008) Transplanted astrocytes derived from BMP- or CNTF-treated glial-restricted precursors have opposite effects on recovery and allodynia after spinal cord injury. J Biol 7: 24. DOI:10.1186/jbiol85