Researchers at the University of California San Diego and at the San Diego Veterans Administration Medical Center have shown that human neural stem cells (NSCs) grafted onto the spinal cord injuries of mice produced a functional recovery after one year. The team has shown that the NSCs continue to grow slowly and steadily even 18 months after implantation.
The study is published in the Journal of Clinical Investigation and set out to answer how long it would take for the cells to mature inside the rodents. Mice and humans have a very different pace when it comes to cell biology.
"The NSCs retained an intrinsic human rate of maturation despite being placed in a traumatic rodent environment," lead author Professor Paul Lu said in a statement. "That's a finding of great importance in planning for human clinical trials."
The researchers were worried that the animal model would not reflect the how this approach might in the future work in humans. For example, pregnancies last 21 days in mice and 280 days in humans. And the weight of a toddler’s brain is comparable with that of a 20-day-old mouse.
"Most NSC grafting studies have been short-term, measuring survival times in weeks to a few months," added co-author Professor Mark Tuszynski. "That's not enough time to fully measure the growth and maturation rate of human NSCs or what changes might occur farther out from the original grafting. These are important considerations, not just for the basic science of stem cell biology, but for the practical design of translational human trials using NSCs for spinal cord injuries."
The researchers report that the cells maintained their natural maturation pace even though they were in a “foreign” environment. That’s why it took several months for the lesions to begin healing. The scientists noted that improvement in the mice mobility only happened after more mature nerve cells formed. As the grafts aged, they displayed the expected pruning and cell redistribution activities that help the development of fewer but more mature cells.
"The bottom line is that clinical outcome measures for future trials need to be focused on long time points after grafting," said Tuszynski. "We need to take into account the prolonged developmental biology of neural stem cells. Success, it would seem, will take time."
The team noticed that none of the implanted NSCs migrated from the graft but some supportive astrocytes cells did, which could be a potential safety concern. No tumors or anomalous formation were created by these cells and modified grafting should fix the problem. A better understanding of this approach, so that the results can be carefully assessed, is required before we can even think to try it on humans.