By Scott LaFee
Lengthy study finds that implanted neural stem cells grow slow and steady, and success needs to be measured accordingly
More than one-and-a-half years after implantation, researchers at University of California San Diego School of Medicine and the San Diego Veterans Administration Medical Center report that human neural stem cells (NSCs) grafted into spinal cord injuries in laboratory rats displayed continued growth and maturity, with functional recovery beginning one year after grafting.
The findings are published in the September issue of the Journal of Clinical Investigation. Prolonged human neural stem cell maturation supports recovery in injured rodent CNS
“The NSCs retained an intrinsic human rate of maturation despite being placed in a traumatic rodent environment,” said Paul Lu, PhD, associate professor of neurosciences and lead author of the study. “That’s a finding of great importance in planning for human clinical trials.”
Neural stem cells differentiate into neurons and glia or support cells. Researchers like Lu and colleague, Mark Tuszynski, MD, PhD, professor of neuroscience and director of the UC San Diego Translational Neuroscience Institute, have explored their potential as a sort of patch and remedy for spinal cord injuries, implanting NSCs derived from induced pluripotent stem cells into animal models of spinal cord injuries to repair damage. In previously published animal studies, Lu and Tuszynski have shown NSCs can survive implantation and make new connections, even beginning to restore limited physical function, such as foot movement, that had been lost to paralyzing injury.
But major questions remained: At what rate do the NSCs mature? And for how long? Rat biology works at a much faster pace than human. The gestational period for a human is 280 days; for a rat, it’s 21. The brain of a 2- or 3-year-old human child is comparable in body/brain weight ratios to a 20-day-old rat. It was possible that human NSCs in animal models would not accurately reflect functioning in future human patients.
“Most NSC grafting studies have been short-term, measuring survival times in weeks to a few months,” said 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. We need to better understand the long-term nature and time course so that we can accurately assess results and success.”
See related commentary: Patient Pays In Spinal Cord Injury