Old concepts revisited and new models

The Tuszynski lab went a little old school in a couple of papers presented during today's morning session. Verena Haringer (#158.10) from the group presented on the properties of cells they had isolated from rodent embryonic spinal cord tissue. Tissue from the cord was dissociated and progenitor cells isolated and grown up. They found these cells would spontaneously become neuronal cell lineages. They could manipulate these to form an excitatory class of neuronal cell which they hoped might form connected neuronal circuit relays after transplantation to re-establish signal transmission lost after trauma to the spinal cord. Despite the tendency of these embryonic cord progenitor cells to turn into neutrons in culture, unfortunately when transplanted into the injured cord they formed non-neuronal cell types (predominately of a glial lineage). One key experiment that needs to be done is to graft these cells into the uninjured cord to see if it is biological signals arising from the damage that ensures this fate or something more general to the in vivo setting.

Switching tack just slightly, Paul Lu (#158.11) from the same group took tissue from E14 rats (embryonic cord tissue) and grew up neuronal cells which they grafted (via injection) into a complete transection (T3) injury. One of the key questions they were asking was, do neurons have an intrinsic capacity to overcome the inhiitory injury environment of the adult CNS? After injection, cells survived and matured, but did not migrate. These grafted cells sent out large numbers of axonal projections over remarkably long distances, both up and down the cord from the injection site. They studied possible mechanisms and established that mTOR signalling was at least partially involved in this rebust ability to grow long axons. Importantly, they found evidence for integration and synapse formation between host and graft cells as well as electrophysiological evidence that these synapses functioned appropriately. As a result the animal recovered some hindlimb function. One of the advantages of this work was te availability of transgenic strains that allowed the graft cells to come pre-labelled with a flourescent marker making identification of the graft cells more positive.

There were also a few posters describing the use of pigs as a model for SCI. Much has been learned from our study of the consequences of injury in the rodent but some in the field are now using pigs to help establish and refine surgical procedures and confirm safety etc.. The pig is significantly larger than the rodent and therefore closer in anatomical scale to humans. It also has a greater volume of cerebral spinal fluid (CSF) and amenable to training so that functional outcomes can be assessed. Brain Kwon (J. Lee #160.04) and others are developing standard outcome scores so that severity of injury and recovery can be better assessed. The use of this larger species may prove to be a useful translational tool.