Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cell Transplants Remyelinate and Restore Locomotion after Spinal Cord Injury

By H. Keirstead, G. Nistor, G. Bernal, Minodora O. Totoiu, Frank Cloutier, K. Sharp, O. Steward. Journal of Neuroscience, 2005

1,248 citations recorded by the source corpus.

Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin-forming cells. Here, we show that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.

Subfields: Developmental Neuroscience, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ef7c2b392d6f8653537182b414be4af112074aa0

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Citations in the corpus

The effect of substrate stiffness on adult neural stem cell behavior. (2009, background): “Already implantation in spinal cord injured rats of oligodendrocyte progenitor cells (OPCs), induced from human embryonic stem cells, has demonstrated enhanced remyelination and partial restoration of locomotion [53].”
A fresh look at iPS cells. (2009, background): “The therapeutic effects of human ES cellderived progeny have been reported in animal models of spinal cord injury (Keirstead et al., 2005), retinal disease (Lamba et al., 2009), and Parkinson’s disease (Yang et al., 2008).”
Generation of functional human pancreatic β cells in vitro (2014, background): “…of arrhythmias with stem-cell-derived cardiomyocytes (Shiba et al., 2012), restoration of locomotion after spinal injury with oligodendrocyte progenitors (Keirstead et al., 2005), or improved vision after transplantation of retinal epithelial cells into rodent models of blindness (Lu et al., 2009).”
Stem cells for the treatment of neurological disorders (2006, background): “Another study reported that transplanted oligodendrocytes from human ES cells could myelinate the injured rodent spinal cord and improve motor functio”
Delayed Transplantation of Adult Neural Precursor Cells Promotes Remyelination and Functional Neurological Recovery after Spinal Cord Injury (2006, neutral): “Recent findings by Keirstead et al. (2005) also showed that even when transplanted cells from an hESC source survived after chronic SCI and differentiated into oligodendrocytes, they failed to remyelinate axons or promote functional recovery.”
Self-Assembling Nanofibers Inhibit Glial Scar Formation and Promote Axon Elongation after Spinal Cord Injury (2008, background): “Regardless of the mech- anisms, the increased number of OLs at the site of injury could facilitate remyelination of axons that traverse the lesion (Keirstead and Blakemore, 1999; Keirstead et al., 2005; KarimiAbdolrezaee et al., 2006).”