Researchers from the University of California San Diego School of Medicine (UCSD; CA, USA) have reported that they have successfully created spinal cord neural stem cells (NSCs) from human pluripotent stem cells (hPSCs) that are able to differentiate into a diverse population of cells capable of dispersing throughout the spinal cord, and can be maintained for long periods of time.
In the study, which was published in Nature Methods, researchers grafted cultured hPSC-derived NSCs into injured spinal cords of rats. They reported that these grafts were rich with excitatory neurons, extended large numbers of axons over long distances, innervated their target structures and enabled robust corticospinal regeneration.
In addition to this, the researchers specified that the grafts synaptically integrated into multiple host instraspinal and supraspinal systems, including the corticospinal projection, and improved function outcomes after injury.
This achievement advances not only basic research, such as biomedical applications of in vitro disease modelling, but may constitute an improved, clinically translatable cell source for replacement strategies in spinal cord injuries and disorders.
“We established a scalable source of human spinal cord NSCs that includes all spinal cord neuronal progenitor cell types,” commented Hiromi Kumamaru (UCSD), first author of the study. “In grafts, these cells could be found throughout the spinal cord, dorsal to ventral. They promoted regeneration after spinal cord injury in adult rats, including corticospinal axons, which are extremely important in human voluntary motor function. In rats, they supported functional recovery.”
Mark Tuszynski (UCSD), senior author of the study, believes that although more work needs to be done, these newly generated cells will constitute source cells for advancement to human clinical trials on a time frame of 3–5 years.
Whether these cells are safe over long time periods in rodents and non-human primates, and whether their efficacy can be replicated, is yet to be determined.
Tuszynski noted that the work presents potential benefits beyond spinal cord injury therapies, since the NSCs can be used in modeling and drug screening for disorders that also involve spinal cord dysfunction (e.g., amyotrophic lateral sclerosis, progressive muscular atrophy, hereditary spastic paraplegia and spinocerebellar ataxia).
Sources: Kumamaru H, Kadoya K, Adler AF et al. Generation and post-injury integration of human spinal cord neural stem cells. Nat. Methods doi:10.1038/s41592-018-0074-3 (2018) (Epub ahead of print); https://ucsdnews.ucsd.edu/pressrelease/created_line_of_spinal_cord_neural_stem_cells_shows_diverse_promise
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