Cell-based therapy for SCI

The morning’s session on the final day of SfN2010 included a number of posters on cell transplantation strategies for SCI.

Schwann cells derived from skin precursors (SKP-SCs) have been reported to improve outcomes despite less than 20% cell survival in the damaged cord. Sparling sought to improve SKP-SC with Neuregulin and other co-treatments expected to enhance graft survival.

With the various co-treatments the group found cell survival and cell bridges extending above and below the lesion cavity but no significant increase in graft volume. Despite this, of all the different treatment groups SKP-SCs + Neuregulin appeared to have the least “variability” and largest average graft volume. In other words, there might be a trend towards increased cell survival. In terms of mechanism, evidence of transplanted SKP-SCs myelinating axons was presented as was increased endogenous Schwann cells (ie those coming into the cord from the periphery where they normally reside).

P. Assinck (from the same lab) examined the fate and outcomes following SKP-SC transplant into the chronic injury. They took rats and transplanted one million cells into the lesion site 8 weeks after thoracic contusion injury. SKP-SCs prevented the decline of forelimb and hindlimb stride length (Catwalk) and elicited a trend towards higher BBB scores, which reached significance in week 17 and 19 after injury. SKP-SCs survived for 21 weeks post injury in all transplanted animals albeit to various degrees. As with acute transplantation, SKP-SCs appeared to facilitate the recruitment of endogenous Schwann cells in the injured cord, and it certainly looked like SKP-SCs modified the Glial scar (less astrocyte hypertrophy in areas containing the transplanted SKP-SCs).

SKP-SCs are suggested as a potentially useful (autologous) source of cells but one must assume we are really only going to isolate from the patient and expand in culture after the injury. As cell expansion will take some time the viability of these cells as a treatment is dependant on being effective in the sub-acute/chronic injury environment making the observation presented here all the more important.

Stephen Davies continued his work on the importance of knowing and controlling the growth conditions of developing astrocytes. Previous work had shown that astrocytes grown in different media end up with quite distinct properties. If you take precursor cells and drive growth using BMP the resultant astrocytes have some beneficial properties. By contrast, if they are grown in the presence of CNTF they can cause undesirable side effects such as pain. The work presented today centred once again on characterisation these two astrocyte populations but this time derived from human fetal cells. Human derived astrocytes generated via BMP induction promoted neuroproetction and recovery in a rat SCI models whilst those induced with CNTF failed to promote locomotor function, in line with that found using rodent tissue. Rodent tissue is not going to be used in humans so confirming human cells have the same properties is an important step towards translation.

There was also a little buzz around a poster from P Lu. Embryonic spinal cord neurons when transplanted into the spinal cord faciliate robust growth of long axons descending the cord into the graft. Less is known about how these cells react within the injured environment or whether they themselves send out axons and integrate functionally. To help answer this, Lu and colleagues used embryonic spinal cord cells from rats that have been infected with a virus that carries a green fluorescent protein (GFP) so they could visualise the fate of embryonic spinal cord cells after transplantation. They transplanted these cells into an injury and found they threw out axons over remarkably long distances and moreover they form synapses with host neurons, become myelinated, connect into the grey matter. What is significant is that these embryonic cells clearly find the so-called inhibitory mature nervous system permissive to regeneration and may be capable of forming functional relays connecting host circuits above and below the injury that were previously disconnected.