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Human induced pluripotent stem cell-derived GABAergic interneuron transplants attenuate neuropathic pain.
Pain 2020; 161(2):379-387PAIN

Abstract

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.

Authors+Show Affiliations

The Dr. John and Anne Chong Laboratory for Functional Genomics, Charles Perkins Centre and School of Life & Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.The Dr. John and Anne Chong Laboratory for Functional Genomics, Charles Perkins Centre and School of Life & Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.Charles Perkins Centre and School of Life & Environmental Sciences, The University of Sydney, New South Wales, Australia.The Dr. John and Anne Chong Laboratory for Functional Genomics, Charles Perkins Centre and School of Life & Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.The Dr. John and Anne Chong Laboratory for Functional Genomics, Charles Perkins Centre and School of Life & Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.The Dr. John and Anne Chong Laboratory for Functional Genomics, Charles Perkins Centre and School of Life & Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.Kirby Neurobiology Centre, Boston Children's Hospital and Department of Neurobiology Harvard Medical School, Boston, United States.Charles Perkins Centre and School of Life & Environmental Sciences, The University of Sydney, New South Wales, Australia.The Dr. John and Anne Chong Laboratory for Functional Genomics, Charles Perkins Centre and School of Life & Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.The Dr. John and Anne Chong Laboratory for Functional Genomics, Charles Perkins Centre and School of Life & Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31972853

Citation

Manion, John, et al. "Human Induced Pluripotent Stem Cell-derived GABAergic Interneuron Transplants Attenuate Neuropathic Pain." Pain, vol. 161, no. 2, 2020, pp. 379-387.
Manion J, Khuong T, Harney D, et al. Human induced pluripotent stem cell-derived GABAergic interneuron transplants attenuate neuropathic pain. Pain. 2020;161(2):379-387.
Manion, J., Khuong, T., Harney, D., Littleboy, J. B., Ruan, T., Loo, L., ... Neely, G. G. (2020). Human induced pluripotent stem cell-derived GABAergic interneuron transplants attenuate neuropathic pain. Pain, 161(2), pp. 379-387. doi:10.1097/j.pain.0000000000001733.
Manion J, et al. Human Induced Pluripotent Stem Cell-derived GABAergic Interneuron Transplants Attenuate Neuropathic Pain. Pain. 2020;161(2):379-387. PubMed PMID: 31972853.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human induced pluripotent stem cell-derived GABAergic interneuron transplants attenuate neuropathic pain. AU - Manion,John, AU - Khuong,Thang, AU - Harney,Dylan, AU - Littleboy,Jamie B, AU - Ruan,Travis, AU - Loo,Lipin, AU - Costigan,Michael, AU - Larance,Mark, AU - Caron,Leslie, AU - Neely,G Gregory, PY - 2020/1/24/entrez PY - 2020/1/24/pubmed PY - 2020/1/24/medline SP - 379 EP - 387 JF - Pain JO - Pain VL - 161 IS - 2 N2 - 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. SN - 1872-6623 UR - https://www.unboundmedicine.com/medline/citation/31972853/Human_induced_pluripotent_stem_cell-derived_GABAergic_interneuron_transplants_attenuate_neuropathic_pain L2 - http://dx.doi.org/10.1097/j.pain.0000000000001733 DB - PRIME DP - Unbound Medicine ER -