Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants improve recovery after cervical spinal cord injury.
Evidence that cell transplants can improve recovery outcomes in spinal cord injury (SCI) models substantiates treatment strategies involving cell replacement for humans with SCI. Most pre-clinical studies of cell replacement in SCI examine thoracic injury models. However, as most human injuries occur at the cervical level, it is critical to assess potential treatments in cervical injury models and examine their effectiveness using at-level histological and functional measures. To directly address cervical SCI, we used a C5 midline contusion injury model and assessed the efficacy of a candidate therapeutic for thoracic SCI in this cervical model. The contusion generates reproducible, bilateral movement and histological deficits, although a number of injury parameters such as acute severity of injury, affected gray-to-white matter ratio, extent of endogenous remyelination, and at-level locomotion deficits do not correspond with these parameters in thoracic SCI. On the basis of reported benefits in thoracic SCI, we transplanted human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into this cervical model. hESC-derived OPC transplants attenuated lesion pathogenesis and improved recovery of forelimb function. Histological effects of transplantation included robust white and gray matter sparing at the injury epicenter and, in particular, preservation of motor neurons that correlated with movement recovery. These findings further our understanding of the histopathology and functional outcomes of cervical SCI, define potential therapeutic targets, and support the use of these cells as a treatment for cervical SCI.
Sharp
Jason
J
Reeve-Irvine Research Center, Sue and Bill Gross Stem Cell Research Center, Department of Anatomy & Neurobiology, School of Medicine, 2111 Gillespie Neuroscience Research Facility, University of California at Irvine, Irvine, California 92697-4292, USA.
Frame
Jennifer
J
Siegenthaler
Monica
M
Nistor
Gabriel
G
Keirstead
Hans S
HS
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement; D002470:Cell Survival; D002574:Cervical Vertebrae / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000637:transplantation*; D005260:Female; D005552:Forelimb / Q000294:innervation; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D009043:Motor Activity; D009046:Motor Neurons / Q000378:metabolism; D009416:Nerve Regeneration; D009836:Oligodendroglia / Q000378:metabolism / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D033581:Stem Cell Transplantation; D013997:Time Factors
D015415:Biomarkers