Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury.
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.
Keirstead
Hans S
HS
Department of Anatomy and Neurobiology, Reeve-Irvine Research Center, College of Medicine, University of California at Irvine, Irvine, California 92697-4292, USA. hansk@uci.edu
Nistor
Gabriel
G
Bernal
Giovanna
G
Totoiu
Minodora
M
Cloutier
Frank
F
Sharp
Kelly
K
Steward
Oswald
O
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000378:metabolism; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D008124:Locomotion / Q000502:physiology*; D009186:Myelin Sheath / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000502:physiology* / Q000637:transplantation; D009842:Oligopeptides / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D055757:SOXE Transcription Factors; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D006609:High Mobility Group Proteins; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; D010751:Phosphopyruvate Hydratase; D055757:SOXE Transcription Factors; D014157:Transcription Factors; C498633:Olig1 protein, rat; C111711:RNAIII inhibiting peptide; C527923:SOX10 protein, human; C527925:Sox10 protein, rat