AUG 30, 2016 08:00 AM PDT

Transplanted human stem cell-derived interneuron precursors mitigate mouse bladder dysfunction and central neuropathic pain after spinal cord injury

  • Co-Founder and Chief Scientific Officer, Neurona Therapeutics, Assistant Professor, Adjunct, University of California, San Francisco, United States
      Dr. Cory Nicholas is Chief Scientific Officer at Neurona Therapeutics. Prior to launching Neurona, Dr. Nicholas was a faculty member in the Department of Neurology at the University of California, San Francisco, where his research program was focused on elucidating the ontogeny of human cortical interneurons. Using embryonic brain development as a blueprint, Dr. Nicholas pioneered methods to derive interneuron precursors from human pluripotent stem cells and developed transplantation cell-based therapies for multiple animal models of neurological disease. He maintains an adjunct faculty appointment at the university. Dr. Nicholas's post-doctoral studies were conducted at UCSF. His pre-doctoral work at both UCSF and Stanford University investigated germ cell development from both primordial germline and pluripotent stem cells. He received his Bachelor's degree from the University of California, Berkeley. Prior to his interest in stem cell and developmental biology, Dr. Nicholas was a member of the discovery research team at Sugen, Inc.

    Neuropathic pain and bladder dysfunction represent significant quality of life issues for many spinal cord injury patients. Loss of GABAergic tone in the injured spinal cord may contribute to the emergence of these symptoms. Previous studies have shown that transplantation of rodent inhibitory interneuron precursors from the medial ganglionic eminence (MGE) enhance GABAergic signaling in the brain and spinal cord. Here we look at whether transplanted MGE-like cells derived from human embryonic stem cells (hESC-MGEs) can mitigate the pathological effects of spinal cord injury. We find that six months after transplantation into injured mouse spinal cords, hESC-MGEs differentiate into GABAergic neuron subtypes and receive synaptic inputs, suggesting functional integration into host spinal cord. Moreover, the transplanted animals showed improved bladder function and mitigation of pain-related symptoms. Our results therefore suggest that this approach may be a valuable strategy for ameliorating the adverse effects of spinal cord injury.

    Show Resources
    Loading Comments...