Patient-derived stem cells can traverse spinal cord injury and reach the brain

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An article published this week in Neuron shows that neurons derived from patient-specific stem cells can be transplanted to an injured rat spinal cord and can extend thousands of processes past the site of injury. Though numerous studies of this type have been published,  many with promising results, this study is the first to show such extensive process outgrowth in a spinal cord injury model.

In this paper, researchers from University of California, San Diego, took skin cells from an 86-year-old healthy male patient, and turned these cells into stem cells using a now-popular method published in 2007, a method that earned Shinya Yamanaka a Nobel Prize in 2012. With this technology, scientists are able to take various tissues (skin, blood, etc.) and transform these differentiated cells into a pluripotent stem cell state. Essentially, these transformed cells can then be re-differentiated into any cell of interest, allowing researchers to study human-derived tissue without having to use embryonic stem cells. In this article, the skin cells derived from the 86-year-old male were used to create neural stem cells which were later transplanted to an injured spinal cord of a rat for analysis.

These patient-derived stem cells (termed “induced pluripotent stem cells”, or iPSCs) were used because their specificity to the individual patient could potentially avoid the problems that exist when introducing foreign tissue (the same type of issue that arises with non-match blood transfusions or organ donations) into a human body. Since these cells can be derived from the actual patient, this technology (further down the road) could provide an easy source of useful stem cell treatment.

The UCSD research team first looked at the survival and dispersion of the transplanted cells. The neural precursor cells were still alive 3 months post-transplantation and they were distributed throughout the lesion. Additionally, the cells expressed more mature neuronal markers, meaning that the original precursor cells had started to mature.

Next, the authors looked at the processes of the grafted neural cells, a neuronal feature vital to proper signal processing and communication between neural cells and structures. To do this, the team used a fluorescent protein to visualize the processes of the neurons. This analysis showed that the grafted neural precursors were able to extend processes all the way up to the cortex and olfactory bulb of the brain, a distance that in some places, was equivalent to 26 spinal segments. Perhaps most importantly, the authors showed that these cells were also able to form synapses, a structure necessary for the the transmission of motor information from one cell to another.

Despite the success that this study was able establish in terms of cell survival and process extension, there seemed to be little functional gain when it came to actual movement, something that seemed to be improved in a previous study published by the same group. The authors suggest that the difference in spinal cord injury (hemisection vs transection) or the movement tests themselves could account for these contrasting results. Ultimately, a lot of work remains to be done as this stem cell model has only been well established relatively recently, though the progress made in this short time suggests that the future for this treatment is promising. Importantly, this study adds to this progress, demonstrating that patient-derived neural cells can be transplanted and can successfully extend axonal processes long distances, mimicking the type of process distribution exhibited by resident spinal neurons.




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