Transplanted Human Stem Cell-Derived Interneuron Precursors Mitigate Mouse Bladder Dysfunction and Central Neuropathic Pain after Spinal Cord Injury.
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) enhances 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 6 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 show 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.
Department of Neurological Surgery, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. Electronic address: tfandel@mac.com.
Thomas M
TM
Fandel
Department of Neurological Surgery, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Alpa
A
Trivedi
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA; Neurona Therapeutics, 650 Gateway Boulevard, South San Francisco, CA 94080, USA.
Cory R
CR
Nicholas
Department of Neurological Surgery, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Haoqian
H
Zhang
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Jiadong
J
Chen
Department of Neurological Surgery, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Aida F
AF
Martinez
Department of Neurological Surgery, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA; Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Linda J
LJ
Noble-Haeusslein
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. Electronic address: kriegsteina@stemcell.ucsf.edu.
Arnold R
AR
Kriegstein
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D002470:Cell Survival; D005260:Female; D000066449:Human Embryonic Stem Cells / Q000166:cytology; D006801:Humans; D007395:Interneurons / Q000637:transplantation*; D051379:Mice; D009437:Neuralgia / Q000209:etiology* / Q000473:pathology / Q000628:therapy*; D013119:Spinal Cord Injuries / Q000150:complications*; D033581:Stem Cell Transplantation; D001743:Urinary Bladder / Q000473:pathology / Q000503:physiopathology*
GABA; MGE; allodynia; bladder; conscious cystometry; electrophysiology; human pluripotent stem cells; hyperalgesia; interneuron; spinal cord injury