Journal
PAIN
Volume 161, Issue 2, Pages 379-387Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/j.pain.0000000000001733
Keywords
Human iPSC; Neuropathic Pain; Peripheral Nerve Injury; GABAergic interneurons; Spinal transplantation; Stem cell therapy
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Funding
- John and Anne Chong Fellowship
- National Health and Medical Research Council (NHMRC) project [APP1026310, APP1029672, APP1028887, APP1046090, APP1042416, APP1086851]
- NHMRC career development fellowship II [CDF1111940]
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Neuropathic pain causes severe suffering, and most patients are resistant to current therapies. A core element of neuropathic pain is the loss of inhibitory tone in the spinal cord. Previous studies have shown that foetal GABAergic neuron precursors can provide relief from pain. However, the source of these precursor cells and their multipotent status make them unsuitable for therapeutic use. Here, we extend these findings by showing, for the first time, that spinally transplanted, terminally differentiated human induced pluripotent stem cell-derived GABAergic (iGABAergic) neurons provide significant, long-term, and safe relief from neuropathic pain induced by peripheral nerve injury in mice. Furthermore, iGABAergic neuron transplants survive long term in the injured spinal cord and show evidence of synaptic integration. Together, this provides the proof in principle for the first viable GABAergic transplants to treat human neuropathic pain patients.
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