The iPSCs used were developed from a healthy 86-year-old human male.
According to the team, the study shows progress in debunking the notion that a spinal cord injury necessarily results in permanent dysfunction and paralysis.
“These findings indicate that intrinsic neuronal mechanisms readily overcome the barriers created by a spinal cord injury to extend many axons over very long distances, and that these capabilities persist even in neurons reprogrammed from very aged human cells,” said senior author Mark Tuszynski.
Earlier work has shown that grafted stem cells reprogrammed to become neurons can in fact form new, functional circuits across an injury site, with the treated animals experiencing some restored ability to move affected limbs.
The new findings bring a host of new questions, such as whether axons can be guided and how they will develop, function and mature over longer periods of time.
For the study, the scientists converted skin cells from a healthy 86-year-old man into iPSCs, which possess the ability to become almost any kind of cell.
The iPSCs were then reprogrammed to become neurons, which were subsequently embedded in a ‘matrix’ containing growth factors and grafted into two-week-old spinal cord injuries in rats.
Three months later, researchers examined the post-transplantation injury sites. They found biomarkers indicating the presence of mature neurons and extensive axonal growth across long distances in the rats’ spinal cords, even extending into the brain.
The axons traversed wound tissues to penetrate and connect with existing rat neurons. Similarly, rat neurons extended axons into the grafted material and cells. The transplants produced no detectable tumours.
While numerous connections were formed between the implanted human cells and rat cells, functional recovery was not observed.
Yet lead scientist Paul Lu noted that tests assessed the rats’ skilled use of the hand. Simpler assays of leg movement could still show benefit.
Also, several iPSC grafts contained scars that may have blocked the beneficial effects of new connections. Further research will seek to improve transplantation methods to eliminate scar formation.
The researchers are now trying to identify the most promising neural stem cell type for repairing spinal cord injuries. They are testing iPSCs, embryonic stem cell-derived cells and other stem cell types.
“Ninety-five percent of human clinical trials fail. We are trying to do as much as we possibly can to identify the best way of translating neural stem cell therapies for spinal cord injury to patients”, said Tuszynski.