French researchers have demonstrated for the first time that embryonic cells grafted into the brains of mice with damaged motor cortices can re-establish damaged connections precisely, so that disrupted neural circuitry is reconstructed.
The findings raise the possibility that cell-based therapies could be used to repair the damage that occurs with brain injury, or as a result of various neurodegenerative diseases.
Researchers have experimented with cell transplantation since the early 1970s, particularly to try and develop therapies for Parkinson's Disease. But they have always faced the difficulty of distinguishing between grafted cells and the host tissue.
Gaillard, et al used donor tissue came from transgenic mice that express green fluorescent protein in all neurons. The transplanted cells, and the projections they formed, could, therefore easily be characterized in the host animals.
The French team anaesthetized adult mice, and removed their motor cortices using a suction syringe. Immediately afterwards, motor cortical tissue from donor embryos was transplanted into the lesioned site. Care was taken to maintain the original orientation of the donor tissue during the transplantation.
Analysis of the nervous systems of host animals, by fluorescence microscopy, showed that the donor cells were well integrated into the host motor cortex. Furthermore, the transplanted cells sprouted projections over long distances - through the corpus callosum and into the thalamus, via the brainstem - and these connections retained the the topography found in normal animals. In some of the mice, GFP-positive nerve fibres were found in the spinal cord.
Electron microscopy and antibody staining revealed that the donor cells also formed synaptic connections with the appropriate targets in the host nervous system, and vice versa. These synapses were evidently functional, as the synaptic terminals of host cells contained synaptic vesicles in the immediate vicinity of donor cell bodies and processes. It was also found that nearly one third of the transplanted cells were myelinated.
The origin of the grafted cells appears to be critical for the reconstruction of pathways. Although the cells were removed from embryos, it seems that they were committed to form motor cortical tissue. in earlier studies,the authors showed that grafts from the visual cortex are apparently incapable of restoring degenerating motor pathways.
Other studies of cell transplantation have led to partial recovery of function. Although the researchers who carried out did not investigate the extent to which the grafted cells led to recovery of function, their findings provide an anatomical basis for those earlier studies.
In humans, the most common cause of motor cortical damage is stroke, and the consequence of this is usually hemiplegia, or paralysis in the side of the body opposite to the damaged cortex. Paralysis following stroke is reversible, but cortical damage following brain injury, or as a result of neurodegenerative diseases such as Alzheimer's, Parkinson's or amyotrophic lateral sclerosis, is not.
These findings show that neural transplantation may be a feasible approach for treating such conditions.
Gaillard, A., et al. (2007). Reestablishment of damaged adult motor pathways by grafted embryonic cortical neurons. Nat. Neurosci. doi: 10.1038/nn1970. [Abstract]