Posted on Nov 02, 2018, 6 p.m.
This proof of concept study published in the online edition of the Annals of Neurology has provided intriguing results that will add to the continued stem cell debates.
Johns Hopkins researchers showed that 11 out of 15 adults rats with virally induced hind limb paralysis were able to walk again following treatments with injections into spinal cords with treat mouse embryonic stem cells.
Coaxing mouse embryonic stem cells into forming functional motor neuron circuits extending into skeletal muscle has successfully restored some walking ability to adult paralyzed rats in proof a principle studies of recapturing what happens in early stages of motor neuron development to use to repair damaged nervous systems.
Stem cells have been shown to halt spinal motor neuron degeneration and restore function in animals with spinal cord injury or in models for amyotrophic lateral sclerosis in other studies, but newly generated neurons forming functional connection in adult mammals has never been shown before, according to the researchers.
University of California researchers showed animals with paralyzing spinal injuries had evidence or remyelination of spinal nerves and recovery of some locomotor function when treated with human embryonic stem cell derived oligodendrocyte progenitor cells within 7 days of injury; but those animals receiving progenitor cells after 10 months after an injury had no evidence of remyelination or restoration of walking ability.
This study investigated ways to overcome problems of myelin inhibition of axon growth that has hampered previous attempts, by treating some of the stem cells with dbcAMP and injecting some of the animals with rolipram. Stem cells were delivered into adult rat spinal cords 28 days after paralyzing with NSV infection.
One group of animals also had GDNF injected as an attractant to help guide nurtured embryonic cells into forming functional neuronal pathways, and cyclosporine to prevent rejection of transplanted embryonic stem cells.
Only the animals treated with the cocktail of dbcAMP, rolipram, and GDNF were reported to have had weight gain at 6 months suggesting that they were more mobile and better able to reach food; hind limb grip strength was also improved only in this group. 11 of the 15 animals receiving the full panel were observed to have significant improvement but incomplete recovery from paralysis, with the animals recovering enough muscle strength to bear weight and step in previously paralyzed hind limb on treated side with GDNF but not the contralateral side.
GDNF was concluded to act as a focal attractive cue for embryonic stem cell derived motor axons when coadministered with rolipram and dbcAMP, facilitating establishment of neuromuscular junctions between host and transplant resulting in recovery.
Stem cells have previously been shown to protect at risk neurons, but in ongoing neurodegenerative diseases there is only a small window of time to do so after which there is nothing left to protect; to overcome loss of function lost neurons must be replaced.
Early results are encouraging and offer hope for possible future treatments on spinal cord injuries and demyelinating diseases. It was noted that the method has not been tested in larger animals or humans, and remains unclear whether human embryonic stem cells will respond similarly to that of mouse cells when treated and put into similar environments. Studies are underway to develop a pig model of neuron degeneration.
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