Efficient differentiation of human embryonic stem cells into oligodendrocyte progenitors for application in a rat contusion model of spinal cord injury.
This study utilized a contusion model of spinal cord injury (SCI) in rats using the standardized NYU-MASCIS impactor, after which oligodendrocyte progenitor cells (OPCs) derived from human embryonic stem cell (ESC) were transplanted into the spinal cord to study their survival and migration route toward the areas of injury. One critical aspect of successful cell-based SCI therapy is the time of injection following injury. OPCs were injected at two clinically relevant times when most damage occurs to the surrounding tissue, 3 and 24 hours following injury. Migration and survivability after eight days was measured postmortem. In-vitro immunofluorescence revealed that most ESC-derived OPCs expressed oligodendrocyte markers, including CNPase, GalC, Olig1, O4, and O1. Results showed that OPCs survived when injected at the center of injury and migrated away from the injection sites after one week. Histological sections revealed integration of ESC-derived OPCs into the spinal cord with contusion injury without disruption to the parenchyma. Cells survived for a minimum of eight days after injury, without tumor or cyst formation. The extent of injury and effect of early cell transplant was measured using behavioral and electrophysiological assessments which demonstrated increased neurological responses in rats transplanted with OPCs compared to controls.
Kerr
Candace L
CL
Department of Gynecology and Obstetrics and Stem Cell Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. ckerr@jhmi.edu
Letzen
Brian S
BS
Hill
Christine M
CM
Agrawal
Gracee
G
Thakor
Nitish V
NV
Sterneckert
Jared L
JL
Gearhart
John D
JD
All
Angelo H
AH
D000818:Animals; D000941:Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000502:physiology*; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D005260:Female; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019081:O Antigens / Q000378:metabolism; D009836:Oligodendroglia / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000379:methods; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D005732:Gangliosides; D009419:Nerve Tissue Proteins; D019081:O Antigens; D011509:Proteoglycans; D020796:Receptor, Platelet-Derived Growth Factor alpha; D055757:SOXE Transcription Factors; D000099216:Chondroitin Sulfate Proteoglycan 4; C527923:SOX10 protein, human; C062875:ganglioside A2B5