Gene jumpstarts regeneration of damaged nerve cells


Searching the entire genome, a Yale research team has identified a gene that when eliminated can spur regeneration of axons in nerve cells severed by spinal cord injury.

For the first time, the limits on nerve fiber regeneration were studied in an unbiased way across nearly all genes,” said Stephen Strittmatter, the Vincent Coates Professor of Neurology and senior author of the study appearing April 10 in the journal Cell Reports. “We had no idea whether we knew a lot or a little about the mechanics of nerve cell regeneration.”

The Yale team found more than 580 different genes that may play a role in regeneration of axons in nerve cells, something that rarely occurs in adult mammals but is of vital interest to scientists hoping to repair injuries to the central nervous system. Intriguingly, said the researchers, about one in 10 of those came from a family of genes involved in transport of information within cells. The researchers also reported that eliminating one of those genes, Rab27, led to regeneration of axons in the optic nerve or spinal cord of mice.

We only looked at this one gene, and we have hundreds more to investigate,” Strittmatter said. “It is not hard to envision an approach where you can knock down two or three of these pathways and help spur regeneration further than achieved previously.”

The work was primarily funded by the National Institutes of Health.

Yale’s Yuichi Sekine is lead author of the paper.

Technology Networks Article

Reference: Sekine, Y., Lin-Moore, A., Chenette, D. M., Wang, X., Jiang, Z., Cafferty, W. B., … Strittmatter, S. M. (2018). Functional Genome-wide Screen Identifies Pathways Restricting Central Nervous System Axonal Regeneration. Cell Reports, 23(2), 415–428.


UCLA researchers find a way to repair nerve damage with stem cells


UCLA researchers have developed a way to use stem cells to help potentially rebuild damaged spinal cords.

In a study published in January, researchers in the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research established a way to derive sensory


interneurons, which are cells involved in reflexes and relaying sensory information to the brain, from stem cells. The researchers identified a specific signaling molecule that caused the stem cells to mature into sensory interneurons.

Stem cells are young cells that can differentiate, or mature, into specific cell types, such as blood cells or neurons, according to the National Institutes of Health. Learning how to differentiate stem cells into specific neuron types is important for some therapies for spinal cord injuries that replace old or damaged tissues with young and healthy cells, according to the study.

Spinal cord injuries cost $40 billion in health care annually in the United States, according to the study. Current therapies focus on protecting the spinal cord from further damage, while stem cell therapies have the potential to reverse and repair damage by replacing damaged cells with new ones.

Samantha Butler, a professor of neurobiology and senior author of the study, said sensory interneurons are involved in fast reflexes, like moving your hand away from heat. They process information and either react immediately or pass the information to the brain for further analysis, she added.

Butler said other researchers have already found ways to differentiate stem cells into other kinds of neurons, but had not yet found a way to differentiate stem cells into interneurons.

“Directing stem cells into spinal motor neurons was developed a while ago,” Butler said. “But how to differentiate stem cells into sensory interneurons was really an open question – a protocol needed to be developed.”


Stem Cell Reports Full Article:

Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem Cells

Restorative effects of human neural stem cell grafts on the primate spinal cord

We grafted human spinal cord–derived neural progenitor cells (NPCs) into sites of cervical spinal cord injury in rhesus monkeys (Macaca mulatta). Under three-drug immunosuppression, grafts survived at least 9 months postinjury and expressed both neuronal and glial markers. Monkey axons regenerated into grafts and formed synapses. Hundreds of thousands of human axons extended out from grafts through monkey white matter and synapsed in distal gray matter. Grafts gradually matured over 9 months and improved forelimb function beginning several months after grafting. These findings in a ‘preclinical trial’ support translation of NPC graft therapy to humans with the objective of reconstituting both a neuronal and glial milieu in the site of spinal cord injury.

Ephron S Rosenzweig, John H Brock, Paul Lu, Hiromi Kumamaru, Ernesto A Salegio, Ken Kadoya, Janet L Weber, Justine J Liang, Rod Moseanko, Stephanie Hawbecker, J Russell Huie, Leif A Havton, Yvette S Nout-Lomas, Adam R Ferguson, Michael S Beattie, Jacqueline C Bresnahan, Mark H Tuszynski.

Restorative effects of human neural stem cell grafts on the primate spinal cord. Nature Medicine, 2018; DOI: 10.1038/nm.4502

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