TY - JOUR
T1 - Efficient differentiation of human embryonic stem cells into oligodendrocyte progenitors for application in a rat contusion model of spinal cord injury
AU - Kerr, Candace L.
AU - Letzen, Brian S.
AU - Hill, Christine M.
AU - Agrawal, Gracee
AU - Thakor, Nitish V.
AU - Sterneckert, Jared L.
AU - Gearhart, John D.
AU - All, Angelo H.
N1 - Funding Information:
We would like to thank the Maryland Stem Cell Research Fund Tedco Number 2007-MSCRFII-0159–00 for funding this work. We also thank Dr. Angelo Lepore for his expertise in cell transplantation, Christopher Lee for help with BBB analysis, and Shrivats Iyer and Anil Maybhate for help with SEP analysis. Address correspondence to Candace L. Kerr, Johns Hopkins University, Obstetrics and Gynecology, 733 N. Broadway, Baltimore, MD 21205, USA. E-mail: [email protected]
PY - 2010/4
Y1 - 2010/4
N2 - 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.
AB - 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.
KW - Contusion
KW - Embryonic stem cells
KW - Motor behavior
KW - Oligodendrocyte
KW - Somatosensory evoked potential
KW - Spinal cord injury
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U2 - 10.3109/00207450903585290
DO - 10.3109/00207450903585290
M3 - Article
C2 - 20374080
AN - SCOPUS:77950816148
SN - 0020-7454
VL - 120
SP - 305
EP - 313
JO - International Journal of Neuroscience
JF - International Journal of Neuroscience
IS - 4
ER -